History of database changes

Tuesday, 20 January 2026 (Version: 20260120AU) (Latest version)

Monday, 19 January 2026 (Version: 20260119AU)

Changed Capmatinib in Non-small cell lung cancer with MET : 4

Alterations changed: CD47-MET fusionCD74-MET fusion.

Monday, 15 December 2025 (Version: 20251215AU)

New Sacituzumab tirumotecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 2

Phase 3 OptiTROP-Lung04 trial. NCT05870319. N=376. Sacituzumab tirumotecan (Sac-TMT) significantly improved PFS (8.3 vs 4.3 months) and OS (not reached vs 17.4 months) compared to platinum-based chemotherapy in EGFR-mutated NSCLC following progression on EGFR-TKIs. References: ESMO25.LBA5

New Disitamab vedotin + Toripalimab in Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 2

Phase 3 RC48-C016 trial. NCT05302284. N=484. Disitamab vedotin + toripalimab significantly improved PFS (13.1 vs 6.5 months) and OS (31.5 vs 16.9 months) over chemotherapy in patients with HER2-expressing locally advanced or metastatic urothelial carcinoma. References: ESMO25.LBA7

New Giredestrant + Everolimus in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

Phase 3 evERA BC trial. NCT05306340. N=373. Giredestrant + everolimus significantly improved PFS over SOC ET + everolimus (8.8 vs 5.5 months) in ER+, HER2- advanced breast cancer patients previously treated with a CDK4/6 inhibitor. References: ESMO25.LBA16

New Gedatolisib + Fulvestrant + Palbociclib, Gedatolisib + Fulvestrant, in Breast cancer with ERBB2+ESR1+PIK3CA PIK3CA:oncogenic mutations + ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

Phase 3 VIKTORIA-1 trial. NCT055001886. N=392. Gedatolisib + fulvestrant with or without palbociclib significantly improved PFS (9.3 vs 2.0 months)in HR+/HER2-/PIK3CA WT advanced breast cancer patients. ORR was 32% (triplet), 28.3% (doublet), and 1% (fulvestrant). References: ESMO25.LBA17

New Sacituzumab tirumotecan in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

Phase 3 OptiTROP-Breast02 study. NCT06081959. N=399. Sacituzumab tirumotecan significantly improved PFS over investigator's choice of chemotherapy (8.3 vs 4.1 months) with a manageable safety profile in patients with previously treated HR+/HER2- breast cancer. References: ESMO25.LBA23

New HRS-7058 in Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal adenocarcinoma, Solid tumour with KRAS G12C: 3

Phase 1 trial. NCT06383871. N=81. HRS-7058, a KRAS G12C inhibitor, showed promising antitumor activity with ORR of 48% and DCR of 94% in KRAS G12Ci-naive NSCLC. 3/4 patients with PDAC had tumour response. References: ESMO25.914O

New HRS-4642 in Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal adenocarcinoma, Solid tumour with KRAS G12D: 3

Phase 1 trial. N=84. HRS-4642, a KRAS G12D inhibitor, showed activity in NSCLC (ORR 24%, mPFS 5.6 months) and PDAC (ORR 21%, mPFS 4.1 months). References: ESMO25.915O

New INCB161734 in Solid Tumours, Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal adenocarcinoma, Ovarian cancer, Solid tumour with KRAS G12D: 3

Phase 1. NCT06179160. N=36. INCB161734, a KRAS G12D inhibitor showed promising efficacy in 36 patients with advanced or metastatic solid tumors, with ORR of 30%, and DCR of 85% achieving disease control at doses ≥600 mg qd (PDAC 34%). References: ESMO25.916O

New Telisotuzumab adizuteca in Solid tumours with MET Amplification: 3

Phase 1 study. NCT05029882. N=100. Temab-A monotherapy showed activities in patients with MET-amplified advanced solid tumors, with a confirmed ORR of 46% and median PFS of 9.5 months across all dose levels and tumor types, including NSCLC (69%) and GEA (71%). References: ESMO25.918O

New DS-3939 in Solid tumours with MUC1 Protein expression: 3

Phase 1/2 FIH study NCT05875168. N=47. DS-3939, a tumour associated-MUC1-directed ADC, showed early signal of clinical activity in pretreated patients with various solid tumors, with 10 confirmed partial responses observed across NSCLC, OC, and BC. References: ESMO25.917O

New SNV1521 in Breast cancer with BRCA2 Oncogenic mutations (germline): 4

Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities. References: ESMO25.923MO

New AMT-116 in Solid tumours with CD44 Protein expression: 4

Phase 1/2 trials (NCT05725291; NCT06782334) of AMT-116, an anti-CD44v9 antibody-drug conjugate, showed manageable safety profile and promising antitumor activity across various solid tumors, with an ORR of 30% in EGFR wild-type NSCLC patients. References: ESMO25.922MO

New SNV1521 in Pancreatic adenocarcinoma with PALB2 Oncogenic mutations (germline): 4

Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities. References: ESMO25.923MO

New SNV1521 in Ovarian cancer with RAD51D Oncogenic mutations (germline): 4

Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities. References: ESMO25.923MO

New Cetuximab, Panitumumab in Colorectal adenocarcinoma with KRAS Amplification: R2

Case report. References: 28178681

New Cetuximab, Panitumumab, FOLFIRI + Cetuximab, Irinotecan + Cetuximab, FOLFOX + Panitumumab in Colorectal adenocarcinoma with NRAS Amplification: R2

Case report. References: 28178681

Saturday, 18 October 2025 (Version: 20251018AU)

New Sevabertinib in Non-small cell lung cancer with ERBB2 Exon 20 insertions, A775_G776insYVMA, Tyrosine kinase domain mutations: 3

Phase 1/2. SOHO-01. NCT05099172. N=209. Three cohorts: D (previously treated without HER2-targeted therapy) had ORR 64%, median duration 9.2 months, PFS 8.3 months; E (previously received HER2 ADCs) ORR 38% with DOR duration 8.5 months, PFS 5.5 months; F (untreated) ORR 71% , with DOR 11.0 months, PFS immature. References: 10.1056/NEJMoa2511065

New Zongertinib in Non-small cell lung cancer with ERBB2 Exon 20 insertions, A775_G776insYVMA, Tyrosine kinase domain mutations: 3

Phase Ib. Beamion LUNG 1. NCT04886804. N=74. First-line zongertinib in treatment-naïve advanced HER2-mutant NSCLC showed ORR 77%, DOR 80%, PFS at 6 months 79%. References: ESMO25.LBA74

New MK-1084 in Non-small cell lung cancer, Colorectal cancer with KRAS G12C: 3

Phase I KANDLELIT-001 trial. NCT05067283. N=123. ORR 38% (CRC), 38% (NSCLC), 34% (others). Median PFS 6.2 (CRC), 8.3 (NSCLC), 5.7 mo. References: ESMO25.926MO

New Divarasib in Solid tumour except Colorectal adenocarcinoma, Non-small cell lung cancer, Pancreatic adenocarcinoma, Cholangiocarcinoma with KRAS G12C: 3

Phase 1. GO42144 (NCT04449874) and JO44179 (jRCT2031220195). N=32. Divarasib showed ORR of 34% (11/32) in KRAS G12C-positive non-NSCLC, non-CRC tumors (pancreatic: 27%, median PFS 7.1 mo; cholangiocarcinoma: 25%, median PFS 7.2 mo). Common TRAEs: diarrhea, nausea, anemia; no Grade 4-5 events. Updated TAPISTRY data (N=47) pending. Cholangiocarcinoma 23% (3/13); Pancreatic adenocarcinoma (31%). Other solid tumour (47%). References: ESMO25.927MO

New HRO761 in Colorectal adenocarcinoma with Microsatellite Instability High: 4

Phase I/Ib. HRO761. NCT05838768. N=47 (19 CRC). ORR 8.6% (10.5% in CRC), DCR 68.6% (84.2% in CRC), median PFS 5.6 months; 9-mo PFS rate 68.6% (95% CI 30.5–88.7) at 200 mg daily. ctDNA clearance observed in 6/14 pts with detectable baseline ctDNA, median treatment duration 9.3 months in responders. References: ESMO25.925MO

Monday, 13 October 2025 (Version: 20251013AU)

Sunday, 12 October 2025 (Version: 20251012AU)

Sunday, 28 September 2025 (Version: 20250928AU)

Changed Dabrafenib + Trametinib in Non-small cell lung cancer with BRAF V600E

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed. Phase 2 trial. NCT01336634. N=36. Dabrafenib + trametinib showed an ORR of 64% (23/36) with a median follow-up of 15.9 months in previously untreated BRAFV600E-mutant metastatic NSCLC.TGA approved. Not PBS reimbursed. Phase 2 trial. NCT01336634. N=36. Dabrafenib + trametinib showed an ORR of 64% (23/36) with a median follow-up of 15.9 months in previously untreated BRAFV600E-mutant metastatic NSCLC..

Changed Selpercatinib in Non-small cell lung cancer with RET Fusion, KIF5B-RET fusion, CCDC6-RET fusion, NCOA4-RET fusion, KIF13A-RET fusion, KIAA1549L-RET fusion, KIAA1468-RET fusion, PRKAR1A-RET fusion

Tier changed: 1B.

Changed Selpercatinib in Non-small cell lung cancer with RET Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion

Tier changed: 1B.

Sunday, 31 August 2025 (Version: 20250831AU)

New Abemaciclib in Leydig cell tumour with CDK4 Amplification: 4

Case report. Targeting CDK4 amplifications in metastatic Leydig cell tumor with abemaciclib showed significant tumor shrinkage (RECIST-equivalent partial response) with no major adverse events. References: 40825166

New Tazemetostat in Ovarian small cell carcinoma with SMARCA4 Loss-of-function mutations: 4

Case report. 32-year-old patient with small-cell carcinoma of ovary hypercalcemic type (SCCOHT) treated with off-label tazemetostat (EZH2 inhibitor) achieved durable response but developed secondary T-cell acute lymphoblastic lymphoma (T-ALL), suggesting dual role of epigenetic therapy in tumor suppression and potential oncogenesis. References: 39167815

Thursday, 21 August 2025 (Version: 20250821AU)

New Larotrectinib in Infantile Fibrosarcoma, Solid Tumors with NTRK1 TMP3-NTRK1 fusion, DCTN1-NTRK1 fusion, LMNA-NTRK1 fusion, BCAN-NTRK1 fusion, TPR-NTRK1 fusion: 3

Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy. References: 39652801

New Larotrectinib in Solid Tumors with NTRK2 AFAP1-NTRK2 fusion: 3

Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy. References: 39652801

New Larotrectinib in Infantile Fibrosarcoma, Solid Tumors with NTRK3 ETV6-NTRK3 fusion, VIM-NTRK3 fusion, EML4-NTRK3 fusion, RBPMS-NTRK3 fusion: 3

Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy. References: 39652801

Monday, 18 August 2025 (Version: 20250818AU)

New Tazemetostat in Solid tumours, Atypical teratoid rhabdoid tumour, Malignant rhabdoid tumor, Ewing sarcoma, Epithelioid sarcoma, Histiocytosis, Renal medullary carcinoma, Hepatocellular carcinoma, Ependymoma, Chordoma, Peripheral T-cell lymphoma with EZH2 Y646C, Y646F, Y646H, Y646N, Y646S, A682G, A682V, A692V: R2

Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%). References: 37228094

New Tazemetostat in Solid tumours, Atypical teratoid rhabdoid tumour, Malignant rhabdoid tumor, Ewing sarcoma, Epithelioid sarcoma, Histiocytosis, Renal medullary carcinoma, Hepatocellular carcinoma, Ependymoma, Chordoma, Peripheral T-cell lymphoma with SMARCB1 Oncogenic mutations, Loss of protein expression: R2

Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%). References: 37228094

New Tazemetostat in Solid tumours, Atypical teratoid rhabdoid tumour, Malignant rhabdoid tumor, Ewing sarcoma, Epithelioid sarcoma, Histiocytosis, Renal medullary carcinoma, Hepatocellular carcinoma, Ependymoma, Chordoma, Peripheral T-cell lymphoma with SMARCA4 Oncogenic mutations, Loss of protein expression: R2

Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%). References: 37228094

Sunday, 17 August 2025 (Version: 20250817AU)

New GSK126, Tazemetostat in Ovarian small cell carcinoma with SMARCA4 Oncogenic mutations: 4

Preclinical study. SCCOHT tumor samples (N=24). 80% (19/24) showed strong EZH2 expression; re-expression of SMARCA4 suppressed EZH2. SCCOHT cells hypersensitive to EZH2 inhibitors (GSK126, EPZ-6438), inducing cell cycle arrest, apoptosis, differentiation, and improved survival in xenograft models. References: 28444909

Friday, 8 August 2025 (Version: 20250808AU)

New VX-970 in Prostate cancer with ATM Oncogenic mutations, Deletion: 4

Preclinical study. ATM loss in prostate cancer models did not significantly increase sensitivity to PARP inhibition but robustly sensitized to ATR inhibition, suggesting ATM-altered tumors may benefit more from ATR inhibitors than PARP inhibitors. References: 32127357

Wednesday, 6 August 2025 (Version: 20250806AU)

Changed Pemigatinib in Cervical cancer with FGFR2 : 3

Alterations changed: C382R (G380R).

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : 3

Alterations changed: C382R (G380R), I291_Y308del, Extracellular domain deletion, Y375C, W290CC382R, I291_Y308del, Extracellular domain deletion, Y375C, W290C.

Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 3

Alterations changed: C382R (G380R), W290CC383R, W290C.

Changed Pemigatinib in Cervical cancer, Endometrial cancer with FGFR2 : 3

Alterations changed: C382R (G380R).

Changed Pemigatinib in Urothelial carcinoma, Glioblastoma, Cervical cancer, Endometrial cancer with FGFR3 : 3

Alterations changed: FGFR3-TACC3 fusion, Y375C (Y373C)FGFR3-TACC3 fusion, FGFR3 Y373C.

Changed Pemigatinib in Urothelial carcinoma with FGFR3 : 3

Alterations changed: Fusion, R248C, S249C, S764fs*6, G372C (G370C), S373C (S371C), Y373C (Y375C)Fusion, R248C, S249C, S764fs*6, G370C, S371C, Y373C.

Changed Erdafitinib in Urothelial carcinoma with FGFR3 : 3

Alterations changed: S249C, Y375C (Y373C), R248C, G372C (G370C), R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusionS249C, Y373C, R248C, G370C, R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusion.

Changed Pemigatinib in Urothelial carcinoma with FGFR3 : 3

Alterations changed: Y375C (Y373C).

Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N549K (N550K)BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K.

Changed Lirafugratinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: FGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D (N550D), N549K (N550K), N549H, V564I, E565A, L617V, K641N, K659MFGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M.

Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: Fusion and N549D (N550D), Fusion and N549K (N550K), Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642I, Fusion and K642R, Fusion and K660MFusion and N550D, Fusion and N550K, Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642I, Fusion and K642R, Fusion and K660M.

Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: Fusion and N549D (N550D), Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642RFusion and N550D, Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642R.

Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: K310R, M537I, N549D (N550D), N549K (N550K), N549H (N550H), V564I, E565A, L617V, K641N, K659MK310R, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M.

Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: K310R, M537I, N549H (N550H), V564I, E565A, L617V, K641N, K659MK310R, M537I, N549H, V564I, E565A, L617V, K641N, K659M.

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: K310R, M537I, N549H (N550H), V564I, K641N, K659MK310R, M537I, N549H, V564I, K641N, K659M.

Changed Gunagratinib in Solid tumours with FGFR2 : 4

Alterations changed: N549H (N550H), V564I, K659NN549H, V564I, K659N.

Changed AZD4547, Infigratinib, E7090, Erdafitinib, Futibatinib, Pemigatinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: N549S, N549H (N550H).

Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: N549H (N550H), N549K (N550K), E566A, E566G, L618M, L618VN550H, N550K, E566A, E566G, L618M, L618V.

Changed Futibatinib in Solid tumours with FGFR2 : 4

Alterations changed: N549H (N550H), V565I, V565L, E566G, K660MN550H, V565I, V565L, E566G, K660M.

Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4

Alterations changed: N549K (N550K), N549D (N550D), K660MN550K, N550D, K660M.

Changed Dovitinib in Endometrial cancer with FGFR2 : 4

Alterations changed: S252W, N549K (N550K), C382R, Oncogenic mutationsS252W, N549K, C382R, Oncogenic mutations.

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N549K (N550K)BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K.

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549K (N550K), N549D (N550D), N549H (N550H), N549F, M537I, V564I, V564F, V564L, L617V, K641R, K569MN549K, N549D, N549H, N549F, M537I, V564I, V564F, V564L, L617V, K641R, K569M.

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549K (N550K), N549H (N550H), E565A, L617V, K641R, K659MN549K, N549H, E565A, L617V, K641R, K659M.

Changed Dovitinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549S, N549H (N550H).

Changed Infigratinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549D (N550D), N549K (N550K), V563I, V565I, V565L, E566A, E566G, K642I, L642R, K660MN550D, N550K, V563I, V565I, V565L, E566A, E566G, K642I, L642R, K660M.

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549D (N550D), N549K (N550K), V565I, V565L, K642I, K660MN550D, N550K, V565I, V565L, K642I, K660M.

Changed Pemigatinib, Infigratinib, Erdafitinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549H (N550H), N549K (N550K), E566A, E566G, L618M, L618VN550H, N550K, E566A, E566G, L618M, L618V.

Changed AZD4547, Infigratinib in Solid tumours with FGFR2 : R2

Alterations changed: N549H (N550H), V565I, V565L, E566G, K660MN550H, V565I, V565L, E566G, K660M.

Changed Pemigatinib,Infigratinib, Erdafitinib, E7090, Zoligratinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549K (N550K), N549D (N550D), K660MN550K, N550D, K660M.

Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: N549K (N550K), V565L, K642I, K660MN550K, V565L, K642I, K660M.

Changed Infigratinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: V564F, N549H (N550H), N549K (N550K), E565A, L617V, K641R, K659MV564F, N549H, N549K, E565A, L617V, K641R, K659M.

Changed Infigratinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: V564F, V564L, N549D (N550D), N549H (N550H), N549K (N550K), E565A, V564I, L617VV564F, V564L, N549D, N549H, N549K, E565A, V564I, L617V.

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: V564F, V564L, N549D (N550D), N549K (N550K), E565A, L617VV564F, V564L, N549D, N549K, E565A, L617V.

Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : R2

Alterations changed: V564F, V564L, N549K (N550K), N549D (N550D)V564F, V564L, N549K, N549D.

Changed Infigratinib, AZD4547, Zoligratinib, Dovitinib, Ponatinib in Solid tumours with FGFR2 : R2

Alterations changed: V565I, N549K (N550K), V564M, V564FV565I, N550K, V564M, V564F.

Wednesday, 30 July 2025 (Version: 20250730AU)

New Daratumumab + Bortezomib + Lenalidomide + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1B

Phase 3 PERSEUS trial. NCT03710603. N=709. Subcutaneous daratumumab added to VRd induction, consolidation, and lenalidomide maintenance significantly improved PFS (84.3% vs 67.7% at 48 months, HR 0.42) and ORR (87.9% vs 70.1%) and MRD-neg ative rate (75.2% vs 47.5%) in transplantation-eligible newly diagnosed multiple myeloma. Note that CD38 is a constitutively expressed target in myeloma and is not required for therapy selection. References: 38084760

New Amivantamab + Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 1B

Phase 3. MARIPOSA. NCT04487080. N=1074. In previously untreated EGFR-mutated NSCLC, a 2:2:1 randomized trial compared amivantamab-lazertinib vs osimertinib vs lazertinib. Amivantamab-lazertinib demonstrated superior PFS compared to osimertinib (23.7 vs 16.6 months; HR 0.70, 95% CI 0.58–0.85). ORR was similar between groups (86% vs 85%), but median response duration favored amivantamab-lazertinib (25.8 vs 16.8 months). OS HR was 0.80 (95% CI 0.61–1.05). References: 38924756

New Enfortumab vedotin + Pembrolizumab in Urothelial carcinoma with NECTIN4 Protein expression: 1B

Not PBS listed. TGA approved for first line therapy with Pembrolizumab. Phase 3 EV-302 trial. NCT04223856. N=886. Enfortumab vedotin + pembrolizumab significantly prolonged PFS (12.5 vs 6.3 months; HR 0.45) and OS (31.5 vs 16.1 months; HR 0.47) versus platinum-based chemotherapy in untreated advanced urothelial cancer. Nectin-4 is constitutively expressed in urothelial carcinoma and biomarker selection is not required. PD-L1 does not have differential predictive effect on therapy outcomes. References: 38446675

New Asciminib in Chronic myelogenous leukaemia with ABL1 BCR-ABL1 Fusion: 2

Phase 3. ASC4FIRST. NCT04971226. N=405. Asciminib achieved a significantly higher major molecular response (MMR) at week 48 (67.7%) vs investigator-selected TKIs (49.0%; difference 18.9%) and vs imatinib (69.3% vs 40.2%; difference 29.6%) in newly diagnosed CML. References: 38820078

New Imlunestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

Phase 3 EMBER-3 trial. NCT04975308. N=874. Imlunestrant (N=331) demonstrated significantly longer PFS than standard therapy in ESR1-mutant patients (5.5 vs 3.8 months; HR 0.70; 95% CI 0.54-0.91; P<0.001) but showed no difference in the overall population (HR 0.87; 95% CI 0.72-1.04; P=0.12). Imlunestrant-abemaciclib combination (N=213) significantly improved PFS over imlunestrant monotherapy (9.4 vs 5.5 months; HR 0.57; 95% CI 0.44-0.73; P<0.001). References: 39660834

New Imlunestrant + Abemaciclib in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

Phase 3 EMBER-3 trial. NCT04975308. N=874. Imlunestrant (N=331) demonstrated significantly longer PFS than standard therapy in ESR1-mutant patients (5.5 vs 3.8 months; HR 0.70; 95% CI 0.54-0.91; P<0.001) but showed no difference in the overall population (HR 0.87; 95% CI 0.72-1.04; P=0.12). Imlunestrant-abemaciclib combination (N=213) significantly improved PFS over imlunestrant monotherapy (9.4 vs 5.5 months; HR 0.57; 95% CI 0.44-0.73; P<0.001). References: 39660834

New Ziftomenib in Acute myeloid leukaemia with KMT2A Rearrangement: 3

Phase 1/2 KOMET-001. NCT04067336. N=83. Ziftomenib showed 25% complete remission or remission with partial hematologic recovery in 36 KMT2A rearrangement/NPM1 mutation patients at 600 mg (recommended phase 2 dose), including 35% remission rate in 20 NPM1 mutation patients. References: 39401509

New Atezolizumab + Carboplatin + Paclitaxel in Endometrial cancer with Mismatch repair Deficient: 2

Phase 3 AtTEnd trial. NCT03603184. N=551. Median PFS was not estimable (95% CI 12.4-NE) for atezolizumab vs 6.9 months (6.3-10.1) for placebo in dMMR endometrial cancer (HR 0.36, p=0.0005); overall PFS 10.1 vs 8.9 months (HR 0.74, p=0.022). Median OS 38.7 vs 30.2 months (HR 0.82, log-rank p=0.048), with trial continuing for OS final analysis. References:

New Ziftomenib in Acute myeloid leukaemia with NPM1 Oncogenic mutation: 3

Phase 1/2 KOMET-001. NCT04067336. N=83. Ziftomenib showed 25% complete remission or remission with partial hematologic recovery in 36 KMT2A rearrangement/NPM1 mutation patients at 600 mg (recommended phase 2 dose), including 35% remission rate in 20 NPM1 mutation patients. References: 39401509

New Belantamab mafodotin + Bortezomib + Dexamethasone in Multiple myeloma with TNFRSF17 Protein expression: 2

Phase 3. DREAMM-7. NCT04246047. N=494. Belantamab mafodotin, bortezomib, dexamethasone (BVd) significantly improved PFS (36.6 vs 13.4 months, HR 0.41) over daratumumab, bortezomib, dexamethasone (DVd) in relapsed/refractory multiple myelo ma, with 84% vs 73% OS at 18 months, 25% vs 10% MRD-negative responses. Note that BCMA is a constitutively expressed target in myeloma and is not required for therapy selection. References: 38828933

New Belantamab mafodotin + Pomalidomide + Dexamethasone in Multiple myeloma with TNFRSF17 Protein expression: 2

Phase 3 DREAMM-8. NCT04484623. N=302. BPd (belantamab mafodotin, pomalidomide, dexamethasone) improved progression-free survival (PFS) over PVd (71% vs 51% at 12 months, hazard ratio 0.52), with higher response rates (77% vs 72%) and deeper responses (40% vs 16% complete response). Note that BCMA is a constitutively expressed target in myeloma and is not required for therapy selection. References: 38828951

New Gedatolisib + Palbociclib + Letrozole, Gedatolisib + Palbociclib + Fulvestrant in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Phase 1b. Dose expansion groups of NCT02684032. N=103. ORR was 85.2% in first-line group A, 61.5% in group B, 25.0% in group C, and 55.6% in group D. Adverse events: neutropenia (63%), stomatitis (27%), rash (20%), and hyperglycaemia (6%). No treatment-related deaths. Responses observed in both wild-type and mutated PIK3CA tumours. References: 38547892

New IMGN632 in Acute myeloid leukaemia with IL3RA Overexpression: 3

Phase 1/2 study. IMGN632. NCT03386513. N=91. Schedule A (n=68), Schedule B (n=23). No maximum tolerated dose defined; 0.045 mg/kg selected as RP2D. ORR 21% (95% CI 8-40; 6/29), composite CR 17% (5/29). Dose-limiting toxicities observed at 0.180, 0.300, 0.450 mg/kg. Phase 1b/2 study initiated with azacitidine and venetoclax in CD123+ AML. Note CD123 expression is not signficantly correlated with response. References: 38423051

New Cabozantinib in Paraganglioma, Phaeochromocytoma with SDHB Oncogenic mutations (germline): 3

Phase 2. Natalie Trial. NCT02302833. N=17. Cabozantinib achieved ORR of 25% (95% CI 7.3–52.4) in 16 evaluable patients with metastatic phaeochromocytoma/paraganglioma (MPPGs). Note the responses are independent of SDHB pathogenic variants, catecholamine secretion, or noradrenaline transporter expression. References: 38608693

New Atezolizumab + Docetaxel + Cisplatin + Fluorouracil in Anal cancer with CD274 Protein expression: 4

Phase 2. SCARCE C17-02 PRODIGE 60. NCT03519295. N=97 (64 in Atezolizumab + mDCF vs 33 in mDCF alone). 12-month PFS 45% (90% CI 35-55) vs 43% (29-58) in group A and B; in PD-L1 CPS ≥5, 70% vs 40% (interaction p=0.051). Higher grade 3-4 adverse events in group A (61% vs 42%), primary endpoint not met. References: 38547895

New CARv3-TEAM-E T cell in Glioblastoma with EGFR vIII: 4

Phase 1. INCIPIENT. NCT05660369. N=3. CARv3-TEAM-E T cells (dual-targeting EGFRvIII and wild-type EGFR) induced rapid tumor regression (transient in 2/3) with no >grade 3 toxicity; one patient had durable response. Liquid biopsy detected EGFR copy number decline. Contrasts with prior single-antigen CAR T trials limited by tumor heterogeneity and antigen loss. References: 38477966

Changed Capmatinib in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 2

Comments changed: Not TGA approved. FDA approved 10/8/2022. Phase 2. GEOMETRY mono-1. NCT02414139. N=373. ORR in METex14 NSCLC was 68% (60 treatment-naive) and 44% (100 previously treated). Median follow-up 46.4 and 66.9 months respectively.\Not TGA approved; FDA approved 10/8/2022; GEOMETRY mono-1: ORR 41% in 69 previously treated patients. Median DOR 9.7 months. ORR 68% in 28 treatment naive patients. Median DOR 12.6 months.. References changed: 32877583, 39362249, 10.1200/JCO.2019.37.15_suppl.900432877583, 10.1200/JCO.2019.37.15_suppl.9004.

Changed Alpelisib + Fulvestrant in Breast cancer with PIK3CA : 3

Alterations changed: C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y. Comments changed: Phase 2. BYLieve. NCT03056755. N=127 (Cohort A). Alpelisib + fulvestrant met primary endpoint of 6-month PFS (53.8%, 95% CI 44.4–63.0) in PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer post CDK4/6 inhibitor. Median PFS 8.0 months, OS 27.3 months. Adverse events included hyperglycaemia (29%) and rash (10%). Original curation: 2021-04-07. Updated 2025-07-30BYLieve single-arm Phase 2 trial. In PIK3CA mutated HR-positive, HER2-negative metastatic breast cancer after CDK4/6 inhibitor therapy, ORR 17%. Median DOR 6.6 months. Median PFS 7.3 mo.. References changed: 33794206, 39637900.

Friday, 18 July 2025 (Version: 20250718AU)

Changed Therapy in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Therapy changed: NeladalkibNVL-655.

Changed Therapy in Solid tumours, Non-small cell lung cancer with ALK I1171N and D1203N: R2

Therapy changed: NeladalkibNVL-655.

Thursday, 17 July 2025 (Version: 20250717AU)

New Afatinib, Neratinib, Dacomitinib in Solid tumours with ERBB4 E715K, R687K: 4

Preclinical study. Unbiased functional genetics screen identifies rare activating ERBB4 mutations (E715K, R687K) promoting hyperactivity in cell models, growth in 2D/3D cultures, and in vivo tumor growth; all mutants sensitive to pan-ERBB inhibitors afatinib, neratinib, dacomitinib. References: 36860695

New Cinrebafusp alfa in Solid tumours with ERBB2 Overexpression, Amplification: 4

Phase 1. NCT03330561. First-in-human study. Cinrebafusp alfa, a HER2/4-1BB bispecific molecule, was evaluated in N=40 patients with previously treated HER2-positive malignancies. The objective response rate was 12.5%, with confirmed responses of 28.6% at 8 mg/kg and 25.0% at 18 mg/kg. Disease control rate was 52.5%, and maximum tolerated dose was not reached. References: 39235868

Monday, 14 July 2025 (Version: 20250714AU)

Changed Therapy in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4

Therapy changed: RipretinibRepretinib.

Changed Therapy in Gastrointestinal stromal tumour with KIT T670I, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2

Therapy changed: RipretinibRepretinib.

Changed Therapy in Gastrointestinal stromal tumour with PDGFRA D842V, D842V and V654A, D842V and T674R: R2

Therapy changed: Imatinib, Sunitinib, Regorafenib, Ripretinib, Nintedanib, Bezuclastinib, IDRX-42, NB003Imatinib, Sunitinib, Regorafenib, Repretinib, Nintedanib, Bezuclastinib, IDRX-42, NB003.

Friday, 11 July 2025 (Version: 20250711AU)

Changed AZD6422 with CLDN18 Protein expression: 4

Cancer type(s) changed: Gastric cancer, Pancreatic adenocarcinoma, Oesophageal cancerGastric cancer, Pancreatic adenocarcinoma, Oessophageal cancer

Thursday, 10 July 2025 (Version: 20250710AU)

Wednesday, 9 July 2025 (Version: 20250709AU)

New Rucaparib, Olaparib, Talazoparib in Prostate cancer with CDK12 Truncating mutations, Kinase domain mutations: 4

CRISPR/Cas9 models and the TRITON2 trial (N=11) demonstrate that CDK12-deficient prostate cancer cells are more sensitive to PARPi, with biallelic truncation mutants showing higher sensitivity (55% PSA reduction) than kinase domain mutants. In TRITON2, 6 of 11 patients responded, with 4/6 achieving stable disease and 2/6 progressive disease by RECIST. Response to rucaparib monotherapy varied by CDK12 mutation type and zygosity (monoallelic, gene arrangements, biallelic). References: 39321214

New AZD6422 in Gastric cancer, Pancreatic adenocarcinoma, Oessophageal cancer with CLDN18 Protein expression: 4

Preclinical study. AZD6422. NCT05981235. Armored CAR-T targeting CLDN18.2 with TGF-beta resistance and optimized manufacturing showed antitumor activity in patient-derived xenograft models of gastric, pancreatic, and esophageal cancers with varying CLDN18.2 and TGF-beta levels. References: 39321207

Monday, 7 July 2025 (Version: 20250707AU)

New IDRX-42 in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New NB003 in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Repretinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Nintedanib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, T670I, D820A, N822K, A829P, V654A and D820A, V654A and N822K, V654A and A829P: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Sunitinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, T670I, V654A and D820A: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Avapritinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, V654A, D816A, D820A, N822K, A829P, V654A and D820A, V654A and N822K, V654A and A829P, D842V: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Imatinib, Regorafenib in Gastrointestinal stromal tumour with KIT Exon11 deletion: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Bezuclastinib in Gastrointestinal stromal tumour with KIT Exon11 deletion, D820A, A829P: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Avapritinib in Gastrointestinal stromal tumour with PDGFRA D842V: 4

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Imatinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, K642E, V654A, T670I, D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Regorafenib in Gastrointestinal stromal tumour with KIT A502_Y503dup, K642E, V654A, T670I, D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Bezuclastinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, K642E, V654A, T670I, D816A, N822K, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Nintedanib in Gastrointestinal stromal tumour with KIT D816A, A502_Y503dup and N822K, V654A and D816A: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Sunitinib in Gastrointestinal stromal tumour with KIT D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and N822K, V654A and A829P: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Avapritinib in Gastrointestinal stromal tumour with KIT K642E, T670I, A502_Y503dup and N822K, V654A and D816A: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New IDRX-42 in Gastrointestinal stromal tumour with KIT T670I, V654A and D816A, V654A and D820A: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Repretinib in Gastrointestinal stromal tumour with KIT T670I, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New NB003 in Gastrointestinal stromal tumour with KIT T670I, V654A and D820A, V654A and N822K, V654A and A829P: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Avapritinib in Gastrointestinal stromal tumour with PDGFRA D842V and V654A, D842V and T674R: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

New Imatinib, Sunitinib, Regorafenib, Repretinib, Nintedanib, Bezuclastinib, IDRX-42, NB003 in Gastrointestinal stromal tumour with PDGFRA D842V, D842V and V654A, D842V and T674R: R2

Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285

Changed Ivosidenib in Cholangiocarcinoma with IDH1 R132

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months). Update 2025-07-07.TGA approved. Not PBS listed. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months)..

Changed Ivosidenib in Cholangiocarcinoma with IDH1 R132

Tier changed: 1B. Comments changed: TGA approved. PBS listed. Phase 3. ClarIDHy trial. Final OS result. In IDH1 mutant cholangiocarcinoma patients, Ivosidenib resulted in median OS of 10.3 months vs 7.5 months (placebo; adjusted for crossover 5.1 months). Update 2025-07-07TGA approved. Not PBS listed. Phase 3. ClarIDHy trial. Final OS result. In IDH1 mutant cholangiocarcinoma patients, Ivosidenib resulted in median OS of 10.3 months vs 7.5 months (placebo; adjusted for crossover 5.1 months)..

Friday, 4 July 2025 (Version: 20250704AU)

New Crizotinib in Non-small cell lung cancer with MET Exon 14 skipping mutation, Exon 16 mutation, H1094Y, c.3028+1G>T, c.3028+1G>A, c.3028G>A, c.3028+1G>C, C.2888-27_2888-2delinsC, c.2935_2939del, c.2888-14_2888-4del, c.2888-17_2888-6del c.2888-18_2888-9del, c.2888-20_2888-11del, c.3028+1G>C, c.3028G>C, c.3028G>T, c.3028G>C, c.3028+2T>C, C.3028+2T>A, C.3028+2T>A, c.3028+3A>G, c.3280C>T: 3

Phase 2. Drug Rediscovery Protocol. NCT0295234. N=30. Crizotinib achieved clinical benefit in 70.8% of MET-mutated non-small cell lung cancer patients (CB: 70.8% [95% CI, 48.9-87.4]), with ORR 62.5% (95% CI, 40.6-81.2). Median PFS 10.2 months (95% CI, 6.0-20.1), OS 13.0 months (95% CI, 9.0-not available). One CR patient harbored a tyrosine kinase domain mutation (p.H1094Y); others had MET exon 14 skipping mutations. References: 39352721

Wednesday, 2 July 2025 (Version: 20250702AU)

New Lorlatinib, Crizotinib, Alectinib, Ceritinib, Brigatinib, Entrectinib, Repotrectinib, Gilteritinib in Non-small cell lung cancer with LTK CLIP1-LTK fusion: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Alectinib in Non-small cell lung cancer with LTK I565N, F568C, G663A: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Ceritinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, G596R, D597N, G663A: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Gilteritinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, L592F, D597N, L650F, G663A: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Lorlatinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, L592F, G596R, D597N, G663A: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Brigatinib, Entrectinib in Non-small cell lung cancer with LTK I565N, L590M, D597N, G663A: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Repotrectinib in Non-small cell lung cancer with LTK I565N, L590M, L592F, G596R, D597N, G663A: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Crizotinib in Non-small cell lung cancer with LTK L592F: 4

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Brigatinib, Entrectinib in Non-small cell lung cancer with LTK F568C, L592F, G596R, L650F: R2

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Repotrectinib in Non-small cell lung cancer with LTK F568C, L650F: R2

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Gilteritinib in Non-small cell lung cancer with LTK G596R: R2

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Crizotinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, G596R, D597N, L650F, G663A: R2

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Alectinib in Non-small cell lung cancer with LTK L590M, L592F, G596R, D597N, L650F: R2

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Ceritinib in Non-small cell lung cancer with LTK L592F, L650F: R2

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Lorlatinib in Non-small cell lung cancer with LTK L650F: R2

Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808

New Trastuzumab + Nivolumab in Breast cancer, Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 3

Phase Ib. DS8201-A-U105. NCT03523572. N=82. T-DXd (5.4 mg/kg) plus nivolumab 360 mg every 3 weeks showed confirmed objective response rates (cORR) of 65.6% (HER2-positive mBC, cohort 1), 50.0% (HER2-low mBC, cohort 2), and 36.7% (HER2-high mUC who had received prior platinum-based chemotherapy, cohort 3). Median PFS was 11.6 months (cohort 1), 7.0 months (cohort 2), and 6.9 months (cohort 3). Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 20.7% (cohort 1) and 20.0% (cohort 3). In Cohort 4 (n=4, HER2-low advanced urothelial cancer/mUC), 2 responders were also seen. Safety consistent with T-DXd monotherapy, though higher TEAE discontinuation rates observed. References: 39405343

Tuesday, 1 July 2025 (Version: 20250701AU)

New Berzosertib in Solid tumours, Leiomyosarcoma with ARID1A Oncogenic mutation: R2

Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit. References: 39453756

New Berzosertib in Solid tumours, Synovial sarcoma, Non-small cell lung cancer, Pancreatic adenocarcinoma, Ovarian cancer with ATM Oncogenic mutation: R2

Phase 2 trial. NCT03718091. T2 cohort. N=6. ATM-mutant solid tumors treated with Berzosertib had a median PFS of 62 days. No response was seen with stable disease as best response in some patients. References: 39453756

New Berzosertib in Leiomyosarcoma, Osteosarcoma with ATRX Oncogenic mutation: R2

Phase 2 trial. NCT03718091. Cohort T1: ATRX-mutant leiomyosarcoma. N=10. Median PFS was short (62 days) with progressive disease as best response in most patients. Evidence of target engagement by berzosertib was seen, but PFS did not correlate with pCHK1 or other pharmacodynamic biomarkers. Increased SLFN11 expression on-treatment correlated with longer PFS (61 vs 33 days). References: 39453756

New Palbociclib in Solid tumours with CDK4 Amplification: R2

Phase 2. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C. N=43. Palbociclib showed limited activity in CDK4/6-amplified tumors with ORR of 4% (1/25) in centrally confirmed cohort, median PFS 2.0 months and OS 8.8 months; partial responses and stable disease observed only in CDK4-amplified tumors, with CNS tumors noted as potential candidates for further investigation. References: 39437014

New Palbociclib in Solid tumours with CDK6 Amplification: R2

Phase 2. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C. N=43. Palbociclib showed limited activity in CDK4/6-amplified tumors with ORR of 4% (1/25) in centrally confirmed cohort, median PFS 2.0 months and OS 8.8 months; partial responses and stable disease observed only in CDK4-amplified tumors, with CNS tumors noted as potential candidates for further investigation. References: 39437014

New Binimetinib in Low-grade serous ovarian cancer with ERBB3 Amplification: R2

Case series. KRAS-mutated LGSOC patient with MEK inhibitor resistance developed aggressive brain metastases associated with ERBB3 amplification and aberrant ERBB3–MYC signaling, suggesting potential resistance mechanisms and need for combinatorial strategies. References: 31836588

New Berzosertib in Solid tumours, Leiomyosarcoma with FBXW7 Oncogenic mutation: R2

Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit. References: 39453756

New Berzosertib in Solid tumours, Prostate cancer with MYC Amplification: R2

Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit. References: 39453756

New Berzosertib in Gastrointestinal stromal tumour with SDHA Oncogenic mutation: R2

Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756

New Berzosertib in Gastrointestinal stromal tumour with SDHB Oncogenic mutation: R2

Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756

New Berzosertib in Gastrointestinal stromal tumour with SDHC Oncogenic mutation: R2

Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756

New Berzosertib in Gastrointestinal stromal tumour with SDHD Oncogenic mutation: R2

Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756

Changed YL201 with CD276 Protein expression: 3

Cancer type(s) changed: Solid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer, Pulmonary lymphoepithelioma-like carcinomaSolid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer, Lymphoepithelioma-like carcinoma

Monday, 30 June 2025 (Version: 20250630AU)

New MOMA-341 in Solid tumours with Mismatch repair Deficient: 4

Preclinical study. MOMA-341, a novel WRN inhibitor, showed antitumor activity in MSI-H models in preclinical studies. Direct measurement of TA repeat expansions by long-read sequencing outperformed MSI-H status as a predictor of sensitivity, enabling near-perfect prediction of MOMA-341 anti-tumor activity. Note sensitivity based on MMR status is inferred. References: NCT06974110

Sunday, 29 June 2025 (Version: 20250629AU)

New Acimtamig in Peripheral T-cell lymphoma with TNFRSF8 Protein expression: 3

Phase 2 study. NCT04101331. N=108. In patients with CD30-positive relapsed or refractory peripheral T-cell lymphomas, acimtamig exhibited an ORR of 32.4% with a CD30 positivity determined by Ber-H2 targeted IHC with CD30 expression confirmed in ≥1% of tumor cells, and a median DoR of 2.3 months. References: 39531538

New BG-C477 in Solid tumours with CEACAM5 Protein expression: 4

Preclinical study. BG-C477, a CEACAM5-targeting ADC with topoisomerase 1 inhibitor payload, demonstrates cytotoxicity and antitumor efficacy in various CEACAM5-expressing cancer models. First-in-human trial ongoing (NCT06596473). References: 10.1158/1538-7445.AM2025-5461

New Pembrolizumab + Cisplatin + Gemcitabine, Pembrolizumab + Carboplatin + Gemcitabine in Urothelial carcinoma with Tumour Mutational Burden High: 4

Phase 3 KEYNOTE-361 trial. NCT02853305. N=993. Primary endpoints of PFS (HR 0.78, P=0.0033) and OS (HR 0.86, P=0.0407) were not met for pembrolizumab plus chemotherapy versus chemotherapy. TMB as a continuous variable was significantly associated with improved ORR, PFS, and OS in pembrolizumab monotherapy (one-sided P<0.001, P<0.001, P=0.007), with highest benefits observed in patients with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 versus chemotherapy alone. Cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1) were prespecified. References: 39475359

New Pembrolizumab + Cisplatin + Gemcitabine, Pembrolizumab + Carboplatin + Gemcitabine in Urothelial carcinoma with CD274 Protein expression: 4

Phase 3 KEYNOTE-361 trial. NCT02853305. N=993. Primary endpoints of PFS (HR 0.78, P=0.0033) and OS (HR 0.86, P=0.0407) were not met for pembrolizumab plus chemotherapy versus chemotherapy. TMB as a continuous variable was significantly associated with improved ORR, PFS, and OS in pembrolizumab monotherapy (one-sided P<0.001, P<0.001, P=0.007), with highest benefits observed in patients with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 versus chemotherapy alone. Cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1) were prespecified. References: 39475359

Changed Brentuximab Vedotin in Anaplastic large cell lymphomaProtein expression: 1

Biomarker changed: TNFRSF8CD30.

Changed Brentuximab Vedotin in Cutaneous T-cell lymphomaProtein expression: 1

Biomarker changed: TNFRSF8CD30.

Changed Brentuximab Vedotin in Hodgkin’s lymphomaProtein expression: 1

Biomarker changed: TNFRSF8CD30.

Changed YL201 with CD276 Protein expression: 3

Cancer type(s) changed: Solid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer, Lymphoepithelioma-like carcinoma Comments changed: Phase 1/1b trial. NCT05434234 and NCT06057922. N=312. YL201, a B7H3-targeting antibody-drug conjugate, demonstrated antitumor activity in heavily pretreated patients with objective response rates of 63.9% in ES-SCLC, 48.6% in NPC, and 54.2% in LELC, prompting ongoing phase 3 trials for SCLC and NPC. All tumors expressed B7H3, but no significant correlation was seen between B7H3 expression levels and response across different tumour types. Updated 2025-06-29Phase 1. NCT06057922 and NCT05434234. In patients with advanced solid tumors, single agent YL201 aided ORR was 74% in SCLC, 46% in NPC, and 32% in NSCLC (wild type especially in adenocarinoma and LELC); at ≥2.0 mg/kg dose level.. References changed: 40082695, 10.1016/j.annonc.2024.08.672.

Friday, 27 June 2025 (Version: 20250627AU)

New Mivebresib in Small-cell lung cancer with MYC Amplification, Overexpression: 4

Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1. References: 38747975

New Mivebresib in Small-cell lung cancer with MYCN Amplification, Overexpression: 4

Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1. References: 38747975

New Sapanisertib in Non-small cell lung cancer with RICTOR Amplification: 4

Case report with translational studies. RICTOR amplification occurs in 8-13% of lung cancer cases and is associated with sensitivity to mTORC1/2 inhibitors; an 18-year-old patient with RICTOR-amplified lung cancer achieved tumor stabilization for over 18 months with dual mTORC1/2 inhibitors. References: 26370156

New Mivebresib in Small-cell lung cancer with MYCL Amplification, Overexpression: R2

Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1. References: 38747975

Tuesday, 24 June 2025 (Version: 20250624AU)

New Fulvestrant + Abemaciclib in Endometrial cancer with ESR1 Protein expression: 3

Phase 2 study. N=27. Fulvestrant plus Abemaciclib showed promising activity in hormone receptor-positive advanced or recurrent endometrial cancer with an ORR of 44% and median PFS of 9.0 months, with durable responses observed mainly in copy number-low/no specific molecular profile tumors. References: 39561275

New Larotrectinib, Entrectinib, Repotrectinib, Selitrectinib in High-grade gliomas, Low-grade gliomas, Central nervous system cancer with NTRK1 Fusions, TPM3-NTRK2 fusion, TPR-NTRK2 fusion, IRF2BP2-NTRK2 fusion, KIF21B-NTRK2 fusion, LMNA-NTRK2 fusion, MEF2D-NTRK2 fusion, ARHGEF2-NTRK2 fusion, PDP0E4IP-NTRK2 fusion, CGN-NTRK2 fusion, KIRREL-NTRK2 fusion: 3

Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment. References: 39625867

New Larotrectinib, Entrectinib, Repotrectinib, Selitrectinib in High-grade gliomas, Low-grade gliomas, Central nervous system cancer with NTRK2 Fusions, AGAP1-NTRK2 fusion, BEND5-NTRK2 fusion, STRN-NTRK2 fusion, KCTD8-NTRK2 fusion, KANK2-NTRK2 fusion, QKI-NTRK2 fusion, NACC2-NTRK2 fusion, KANK1-NTRK2 fusion, SPEC1L-NTRK2 fusion, GKAP1-NTRK2 fusion, KCTD16-NTRK2 fusion, CHAMP1-NTRK2 fusion, CCDC88A-NTRK2 fusion, DNM3-NTRK2 fusion, SBF2-NTRK2 fusion, UGDH-NTRK2 fusion, STMN1-NTRK2 fusion, ATP6V1A-NTRK2 fusion, VAMP4-NTRK2 fusion, SHANK1-NTRK2 fusion, SORBS1-NTRK2 fusion, ABI2-NTRK2 fusion, GNAI1-NTRK2 fusion, SOS1-NTRK2 fusion, DENND5A-NTRK2 fusion, C1orf112-NTRK2 fusion, TLE1-NTRK2 fusion, PHF20L1-NTRK2 fusion, CYP2E1-NTRK2 fusion, PAPPA-NTRK2 fusion: 3

Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment. References: 39625867

New Larotrectinib, Entrectinib, Repotrectinib, Selitrectinib in High-grade gliomas, Low-grade gliomas, Central nervous system cancer with NTRK3 Fusions, ETV6-NTRK3 fusion, EML4-NTRK3 fusion, BCR-NTRK3 fusion, KANK1-NTRK3 fusion, FOXJ2-NTRK3 fusion, MYO5A-NTRK3 fusion, MN1-NTRK3 fusion, EGR3-NTRK3 fusion, SPEC1L-NTRK3 fusion, SOX6-NTRK3 fusion: 3

Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment. References: 39625867

New Alisertib + Pembrolizumab in Head and neck squamous cell carcinoma with RB1 Deletion, Oncogenic mutations, Loss of protein expression: R2

Phase 1/2 trial. Alisertib + Pembrolizumab demonstrated no objective responses but achieved prolonged stable disease in several patients. Among 15 HPV-positive patients, 4 experienced stable disease ≥6 months. Median overall survival was 16.8 months and median progression-free survival was 1.4 months. References: 39589337

Monday, 23 June 2025 (Version: 20250623AU)

New Sacituzumab Govitecan in Triple-negative breast cancer with TACSTD2 Protein expression, Overexpression: 4

Phase 2 TROPiCS-03 basket trial. NCT03964727. N = 43. Objective response rate was 16% and clinical benefit rate was 28% in heavily pretreated advanced HNSCC patients receiving Sacituzumab Govitecan, with median duration of response, PFS, and OS being 4.2, 4.1, and 9.0 months. Note Trop 2 expression was assesed as an exploratory endpoint. Patients were enroleld prospectively as Trop2 expression is highly expressed in HNSCC. References: 39665770

New Selinexor + Docetaxel in Non-small cell lung cancer with KRAS+TP53 KRAS:Oncogenic mutations and NOT TP53:Alteration: 3

Phase 1/2 trial. N=40. Selinexor plus docetaxel showed activities in TP53 wild-type KRAS-mutant NSCLC patients with a median PFS of 7.4 months versus 1.8 months in TP53-altered cases, and response rates of 27% versus 9% respectively. References: 39651955

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : 3

Alterations changed: Fusion, FGFR2-BICC1 fusion, FGFR2-RBM20 fusion, FGFR2-MRVI1 fusion, FGFR2-CROCC fusion, FGFR2-KIAA1598 fusion, FGFR2 I291_Y308del, FGFR2 W290C, FGFR2 Y375C, FGFR2 C382RFusion, FGFR2-BICC1 fusion, FGFR2-RBM20 fusion, FGFR2-MRVI1 fusion, FGFR2-CROCC fusion, FGFR2-KIAA1598 fusion, FGFR2 1291_Y308del, FGFR2 W290C, FGFR2 Y375C, FGFR2 C382R.

Sunday, 22 June 2025 (Version: 20250622AU)

New Sunitinib in Gastrointestinal stromal tumour with KIT Protein expression: 1

PBS reimbursed based on CD117 (c-KIT) IHC. Randomised controlled Phase 3 trial. NCT00075218. N=312. Median time to tumour progression was 27.3 weeks with sunitinib versus 6.4 weeks with placebo (HR 0.33; p<0.0001) in imatinib-resistant or intolerant gastrointestinal stromal tumour. References: 17046465

New Ipatasertib in Breast cancer, Endometrial cancer with AKT1 E17K: 3

Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers. References: 10.1200/JCO.2024.42.16_suppl.3092

New Ipatasertib in Head and neck squamous cell carcinoma with AKT1 E17K: 4

Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers. References: 10.1200/JCO.2024.42.16_suppl.3092

New Ipatasertib in Solid tumours except Breast cancer, Endometrial cancer with AKT1 E17K: R2

Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers. References: 10.1200/JCO.2024.42.16_suppl.3092

Removed Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF alterations V600E: Tier 2

Removed Ipatasertib in Solid tumours with AKT1 alterations Oncogenic mutations, L52R, Q79K: Tier 4

Removed Ipatasertib in Solid tumours with AKT2 alterations Oncogenic mutations, E17K: Tier 4

Removed Ipatasertib in Solid tumours with AKT3 alterations Oncogenic mutations, E17K, L51R, Q78K: Tier 4

Removed BET inhibitor in Solid tumours with BRD2 alterations Oncogenic mutations: Tier 4

Removed BET inhibitor in Solid tumours with BRD3 alterations Oncogenic mutations: Tier 4

Removed BET inhibitor in Solid tumours with BRDT alterations Oncogenic mutations: Tier 4

Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with STK11 alterations Oncogenic mutations: Tier R2

Changed Ibrutinib in Mantle cell lymphoma with CD20 Protein expression: 1

Comments changed: PBS reimbursed. Phase 2 study. NCT01236391. N=111. Ibrutinib showed a 68% overall response rate (21% complete response, 47% partial response) in patients with relapsed or refractory mantle-cell lymphoma, with median response duration of 17.5 months, median progression-free survival of 13.9 months, and 58% overall survival at 18 months..

Changed Rituximab in Non-Hodgkin’s lymphoma, Chronic lymphocytic leukaemia, Acute lymphoblastic leukaemia, Hodgkin’s lymphoma with CD20 Protein expression: 1

Comments changed: PBS reimbursed. References non-exhaustive..

Changed Atezolizumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:Oncogenic mutations and NOT ALK:fusion

Tier changed: 1B. Comments changed: TGA approved. PBS reimbused. Phase 3 IMpower110 trial (NCT02409342, N=572) evaluated first-line atezolizumab in EGFR and ALK negative NSCLC patients with PD-L1 expression ≥1% on tumor cells or tumor-infiltrating immune cells covering ≥1% of tumor area. Atezolizumab significantly improved median OS compared to chemotherapy (20.2 vs 13.1 months, improvement of 7.1 months).TGA approved; IMPower110: First-line treatment in PD-L1 positive population (defined as positive stain on >=least 1% of tumour cells or tumor-infiltrating immune cells >= 1% of the tumor area), EGFR and ALK negative. Median OS: 20 vs 13 months (chemotherapy).

Changed Brentuximab Vedotin in Hodgkin’s lymphoma with CD30 Protein expression: 1

Comments changed: PBS reimbursed for R/R disease. Phase 3 AETHERA trial: Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation significantly improved PFS (HR 0.57) in patients with Hodgkin's lymphoma at risk of relapse or progression..

Changed Gilteritinib in Acute myeloid leukaemia with FLT3 D835, I836, Internal tandem duplication: 1

Comments changed: PBS reimbursed. Phase 1-2 trial (NCT02014558) demonstrated gilteritinib was well tolerated in patients with relapsed or refractory acute myeloid leukaemia, with a maximum tolerated dose of 300mg/day, consistent FLT3 inhibition and antileukaemic activity, achieving 40% response rate. Phase 3 trial (NCT02421939, N=371) showed gilteritinib significantly improved overall survival (9.3 vs 5.6 months) and complete remission with full or partial hematologic recovery (34.0% vs 15.3%) compared to salvage chemotherapy in patients with relapsed or refractory FLT3-mutated AML.PBS reimbursed in R/R FLT3-mutant AML.

Changed Therapy in Gastrointestinal stromal tumour with KIT Protein expression: 1

Therapy changed: Imatinib, Sunitinib. Comments changed: PBS reimbursed based on CD117 (c-KIT) IHC. Phase 2 trial. N=147. Imatinib mesylate resulted in a partial response in 53.7% of patients with advanced gastrointestinal stromal tumors, with median duration of response not reached after 24 weeks, and was well tolerated with mild-to-moderate adverse effects.PBS reimbursed based on CD117 (c-KIT) IHC. NCCN Category 1. References changed: 12181401, 17046465.

Changed Ripretinib in Gastrointestinal stromal tumour with KIT Protein expression; Oncogenic mutations: 1

Comments changed: TGA approved. PBS Reimbursed for patients with GIST who received prior treatment with 3 or more kinase inhibitors. Phase3 INVICTUS trial. NCT03353753. Ripretinib significantly improved median PFS (6.3 months vs 1.0 month) compared with placebo in patients with advanced gastrointestinal stromal tumours resistant to approved treatments.TGA approved. PBS Reimbursed for patients with GIST who received prior treatment with 3 or more kinase inhibitors;.

Changed Cetuximab, Panitumumab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Comments changed: PBS reimbursed for RAS-wild-type metastatic colorectal cancers. N=329. Cetuximab plus irinotecan had a significantly higher ORR (22.9% vs 10.8%) and longer median TTP (4.1 vs 1.5 months) compared to cetuximab monotherapy in irinotecan-refractory metastatic colorectal cancer. In a meta-analysis of 9 RCTs (N=5948). anti-EGFR mAb therapy significantly improved PFS (HR 0.62) and OS (HR 0.87) in mCRC tumors without any RAS mutations, while no benefit was evident in tumors with RAS mutations..

Changed Enfortumab Vedotin in Urothelial carcinoma with NECTIN4 Protein expression: 1

Comments changed: TGA approved. PBS reimbursed. In Phase 2 EV-201 trial (N=125), enfortumab vedotin showed a confirmed objective response rate of 44% with 12% complete responses in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum and anti-PD-1/L1 therapy. In registrational Phase 3 EV-301 trial (NCT03474107, N=608), enfortumab vedotin significantly prolonged overall survival (12.88 months vs 8.97 months) and progression-free survival (5.55 vs 3.71 months) compared to chemotherapy in patients with advanced urothelial carcinoma previously treated with platinum-containing chemotherapy and PD-1 or PD-L1 inhibitor. Nectin-4 expression was not required for trial entry, given that it is highly expressed on majority of urothelial carcinoma cells.TGA approved. PBS reimbursed. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells..

Changed Imatinib in Chronic eosinophilic leukaemia with PDGFRA FIP1L1-PDGFRA Fusion; Fusion: 1

Comments changed: TGA approved. PBS reimbursed. Phase 2 study. Imatinib was effective in treating CEL with FIP1L1-PDGFRA or PDGFRB fusion genes, achieving 95% CHR and 75-87% CMR, with no molecular relapse observed at a median follow-up of 26.7 months, while HES patients without known molecular aberration showed a lower response rate..

Changed Medroxyprogesterone Acetate in Endometrial cancer with PGR Protein expression: 1

Comments changed: Standard of care. Phase 3 dose-response study. N=299. Oral medroxyprogesterone acetate (MPA) showed response rates of 25% (low-dose, 200mg/d) versus 15% (high-dose, 1000mg/d) in advanced or recurrent endometrial carcinoma, with median PFS of 3.2 and 2.5 months, and median OS of 11.1 and 7.0 months, respectively..

Changed Ibrutinib + Rituximab in Chronic lymphocytic leukaemia with CD20 Protein expression: 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3 trial. NCT02048813. N=529. Ibrutinib-rituximab resulted in superior PFS (89.4% vs 72.9% at 3 years) and OS (98.8% vs 91.5% at 3 years) compared to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab in patients with previously untreated CLL..

Changed Ibrutinib, Ibrutinib + Rituximab in Waldenstroms macroglobulinaemia with CD20 Protein expression: 1B

Comments changed: Phase 3. iNNOVATE trial. N=150. Ibrutinib plus Rituximab significantly improved PFS (HR, 0.20) and major response rate (72% vs 32%) compared to placebo plus Rituximab in both previously treated and untreated Waldenstrom's macroglobulinemia patients..

Changed Pembrolizumab in Cervical cancer with CD274 Protein expression: 1B

Comments changed: TGA approved. In the Phase 1b KEYNOTE-028 trial (NCT02054806; n=24) in PD-L1-positive advanced cervical cancer, pembrolizumab achieved an ORR of 17% (4 confirmed partial responses; 3 stable disease). In the Phase 2 KEYNOTE-158 study (NCT02628067; n=98) in previously treated advanced cervical cancer, pembrolizumab produced an ORR of 12.2% (3 complete responses; 9 partial responses), with all responses occurring in tumors with CPS ≥ 1% by 22C3 pharmDx assay (ORR 15% in PD-L1-positive cohort).TGA approved. KEYNOTE-028: Phase 1b. ORR 17%. KEYNOTE-158: ORR 15%. PD-L1 positivity defined as CPS >= 1% (22C3 pharmDx assay)..

Changed Daratumumab + Lenalidomide + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1B

Comments changed: TGA approved. Phase 3 POLLUX trial. NCT02076009. N=569. Daratumumab + lenalidomide + dexamethasone significantly improved PFS (HR, 0.37) and ORR (92.9% vs 76.4%) compared to lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma..

Changed Isatuximab-irfc + Pomalidomide + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1B

Comments changed: TGA approved. Phase 3 ICARIA-MM study. N = 307. Isatuximab + pomalidomide-dexamethasone significantly improved median PFS (11.5 months) compared to pomalidomide-dexamethasone (6.5 months) with HR of 0.596 in relapsed and refractory multiple myeloma patients.ICARIA-MM trial.

Changed Polatuzumab vedotin + Bendamustine + Rituximab in Diffuse large B-cell lymphoma with CD79B Protein expression: 1B

Comments changed: Standard of care. TGA approved but not based on biomarker. Phase Ib/II trials demonstrated that polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) achieved superior outcomes compared to bendamustine and rituximab in transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma patients: complete response rate (40.0% vs 17.5%), progression-free survival (median 9.5 vs 3.7 months), and overall survival (median 12.4 vs 4.7 months). While CD79B is prognostic, CD79B expression alone does not correlate with response degree.Standard of care. Drug approved by TGA. CD79B is prognostic, but CD79B expression alone not associated with degree of response.

Changed Amivantamab in Non-small cell lung cancer with EGFR Exon 20 insertion: 1B

Comments changed: TGA approved. Not PBS Listed. FDA accelerated approval 2021-05-21. Median PFS 8.3 months. "Phase 1 CHRYSALIS trial. N=81. Amivantamab, an EGFR-MET bispecific antibody, showed an ORR of 40% (3 complete responses) and median DOR of 11.1 months in patients with EGFR Exon20ins NSCLC progressing on platinum chemotherapy, with a median PFS of 8.3 months.TGA approved. Not PBS Listed. FDA accelerated approval 2021-05-21. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months..

Changed Lapatinib + Paclitaxel in Breast cancer with ERBB2 Amplification: 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3. NCT00281658. Lapatinib + paclitaxel significantly improved OS (27.8 vs 20.5 months), PFS (9.7 vs 6.5 months), and ORR (69% vs 50%) compared to placebo + paclitaxel in HER2-positive metastatic breast cancer patients. HER2 positivity determined by FISH.TGA approved. Not PBS reimbursed. NCT00281658: HER2 positivity determined by FISH..

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 Fusions, FGFR2-ACLY fusion, FGFR2-AFF4 fusion, FGFR2-AHCYL1 fusion, FGFR2-ARHGAP22 fusion, FGFR2-ARHGAP24 fusion, FGFR2-ATAD2 fusion, FGFR2-ATF2 fusion, FGFR2-BICC1 fusion, FGFR2-BICD1 fusion, FGFR2-CCDC158 fusion, FGFR2-CCDC170 fusion, FGFR2-CCDC6 fusion, FGFR2-CEP128 fusion, FGFR2-COL16A1 fusion, FGFR2-CTNNA3 fusion, FGFR2-DBP fusion, FGFR2-DNAJC12 fusion, FGFR2-EEA1 fusion, FGFR2-EIF4ENIF1 fusion, FGFR2-FILIP1 fusion, FGFR2-GAB2 fusion, FGFR2-GOPC fusion, FGFR2-INSC fusion, FGFR2-KCTD1 fusion, FGFR2-KIAA1217 fusion, FGFR2-KIAA1598 fusion, FGFR2-LAMC1 fusion, FGFR2-MACF1 fusion, FGFR2-MATR3 fusion, FGFR2-MCU fusion, FGFR2-NEDD4L fusion, FGFR2-NOL4 fusion, FGFR2-NRAP fusion, FGFR2-NRBF2 fusion, FGFR2-PAH fusion, FGFR2-PAWR fusion, FGFR2-POC1B fusion, FGFR2-PXN fusion, FGFR2-RABGAP1L fusion, FGFR2-RASSF4 fusion, FGFR2-RPAP3 fusion, FGFR2-SFI1 fusion, FGFR2-SHROOM3 fusion, FGFR2-SLMAP fusion, FGFR2-SOGA1 fusion, FGFR2-SPICE1 fusion, FGFR2-STRN4 fusion, FGFR2-TACC1 fusion, FGFR2-TFEC fusion, FGFR2-TRIM8 fusion, FGFR2-TTC28 fusion, FGFR2-TXLNB fusion, FGFR2-USH2A fusion, FGFR2-VCL fusion, FGFR2-WAC fusion, FGFR2-WDHD1 fusion, FGFR2-ZMYM4 fusion: 1B

Comments changed: TGA approved. Not PBS reimbused. Phase 2 FIGHT-202 trial. NCT02924376. N=146. Pemigatinib showed an objective response in 35.5% of patients with FGFR2 fusions or rearrangements, with a median follow-up of 17.8 months.TGA approved; Not PBS reimbused; FIGHT-202.

Changed Enasidenib in Acute myeloid leukaemia with IDH2 R140Q, R140, R172K, R172S: 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 1/2 trial. NCT01915498. Enasidenib induced hematologic responses in relapsed/refractory AML patients with mutant IDH2, with an overall response rate of 40.3% and median overall survival of 9.3 months, and was generally well tolerated with grade 3 to 4 adverse events including indirect hyperbilirubinemia and IDH-inhibitor-associated differentiation syndrome.TGA approved. Not PBS reimbursed. For relapsed/refractory AML..

Changed Regorafenib in Gastrointestinal stromal tumour with KIT Protein expression: 1B

Comments changed: PBS reimbursed based on CD117 (c-KIT) IHC. Phase 3 GRID trial. NCT01271712. N=199. Regorafenib significantly improved PFS (4.8 months vs 0.9 months) compared to placebo in patients with metastatic GIST after failure of imatinib and sunitinib.PBS reimbursed based on CD117 (c-KIT) IHC. NCCN Category 1.

Changed Imatinib in Myelodysplastic/myeloproliferative diseases with PDGFRA FIP1L1-PDGFRA Fusion; Fusion: 1B

Comments changed: TGA approved. Not PBS reimbursed. Multicenter prospective study. NCT00276929. Imatinib mesylate achieved complete hematologic remission in 27 FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome patients, with durable responses at 100-400 mg daily, and treatment discontinuation led to rapid reappearance of fusion transcript..

Changed Imatinib in Myelodysplastic/myeloproliferative diseases with PDGFRB Fusions: 1B

Comments changed: TGA approved. Not PBS reimbursed. Retrospective cohort study. N=26. Patients with myeloid malignancies bearing PDGFRB fusion genes treated with imatinib had a 10-year overall survival rate of 90% and 6-year progression-free survival rate of 88% with 96% response rate..

Changed Selpercatinib in Non-small cell lung cancer with RET Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion: 1B

Comments changed: TGA approved. Not PBS reimbursed. FDA Approved 21/09/2022. Phase 1-2 LIBRETTO-001 trial. NCT03157128. Selpercatinib showed an ORR of 64% in 105 previously treated RET fusion-positive NSCLC patients and 85% in 39 previously untreated patients, with durable responses and intracranial activity.TGA approved. Not PBS reimbursed. FDA Approved 21/09/2022. LIBRETTO-001: First-line treatment. ORR 85%..

Changed Elotuzumab + Lenalidomide + Dexamethasone in Multiple myeloma with SLAMF7 Protein expression: 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3 ELOQUENT-2 trial. NCT01239797. N=646. Elotuzumab + lenalidomide + dexamethasone significantly improved PFS (19.4 vs 14.9 months) and ORR (79% vs 66%) compared to lenalidomide + dexamethasone alone in patients with relapsed or refractory multiple myeloma..

Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with Tumour Mutational Burden High: 1B

Comments changed: TGA provisionally approved. Phase 3 CHECKMATE227 trial. Nivolumab + Ipilimumab significantly improved PFS (7.2 vs 5.5 months) and ORR (45.3% vs 26.9%) compared to chemotherapy in NSCLC patients with high TMB (≥10 mut/MB). Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort but outcomes not correlated with TMB.TGA provisionally approved. Phase 3 CHECKMATE 227. Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort. Median PFS: 7.2 vs 5.5 months. Not correlated with TMB..

Changed Dasatinib + Blinatumomab in Acute lymphoblastic leukaemia with ABL1 BCR-ABL1 Fusion: 2

Comments changed: Phase 2 GIMEMA LAL2116 D-ALBA trial. N=63. CR rate 98%. Molecular response rate increased from 29% after dasatinib induction to 60% after 2 cycles of blinatumomab. At 18 months, OS was 95% and DFS was 88%.GIMEMA LAL2116 D-ALBA trial. CR rate 98%. OS 18 month: 95%. DFS: 88%..

Changed Nilotinib in Acute lymphoblastic leukaemia with ABL1 BCR-ABL1 Fusion: 2

Comments changed: Not TGA approved for ALL; Phase 1 dose-escalation study. NCT00109707. N=119. Nilotinib showed activity in imatinib-resistant CML with hematologic and cytogenetic responses observed across various disease phases, and had a relatively favorable safety profile.Not TGA approved for ALL; Positive Phase 3 study.

Changed Dabrafenib + Trametinib in Biliary tract cancers with BRAF V600E: 2

Comments changed: Not TGA approved. Note FDA approval for tumour agnostic indication 23/06/2022. Phase 2 ROAR trial. NCT02034110. N=43. Dabrafenib plus trametinib showed activity in BRAF(V600E)-mutated biliary tract cancer with BICR ORR 47% and manageable safety profile.Not TGA approved. FDA approval for tumour agnostic indication 23/06/22. ROAR. BICR ORR 47%..

Changed Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF V600E: 2

Comments changed: Not TGA approved. FDA approved. Phase 3 BREAKWATER trial (NCT04607421, N=637) demonstrated that encorafenib + cetuximab + mFOLFOX6 significantly improved outcomes compared to standard of care in previously untreated BRAF V600E-mutant metastatic colorectal cancer: ORR (60.9% vs 40.0%), median duration of response (13.9 vs 11.1 months), PFS (12.8 vs 7.1 months), and OS (30.3 vs 15.1 months). Updated 2025-05-31.Not TGA approved. FDA approved. Phase 3 BREAKWATER trial. NCT04607421. Encorafenib + cetuximab + mFOLFOX6 significantly improved ORR over SOC (60.9% vs 40.0%) in previously untreated BRAF V600E-mutant metastatic colorectal cancer, with a median duration of response of 13.9 months versus 11.1 months.. References changed: 39863775, 10.1200/JCO.2025.43.16_suppl.LBA3500.

Changed Dabrafenib + Trametinib in Glioblastoma, High-grade glioma, Low-grade glioma with BRAF V600E: 2

Comments changed: Not TGA approved. Phase 2. ROAR. NCT02034110. Dabrafenib plus trametinib showed ORR of 33% (15/45) in high-grade glioma (32% in glioblastoma) and 69% (9/13) in low-grade glioma, with a safety profile consistent with other indications.Phase 2. ROAR. ORR was 33% (15/45) In high-grade glioma (10/31, 32% in glioblastoma). ORR was 69% (9/13) in the low-grade glioma cohort..

Changed Rucaparib in Prostate cancer with BRCA1 Oncogenic mutations: 2

Comments changed: Not TGA Approved. Phase 2 TRITON2 study. Rucaparib showed antitumor activity in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration, with confirmed ORR of 43.5% and PSA response rate of 54.8%.Not TGA Approved. TRITON2 trial..

Changed Rucaparib in Prostate cancer with BRCA2 Oncogenic mutations: 2

Comments changed: Not TGA Approved. Phase 2 TRITON2 study. Rucaparib showed antitumor activity in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration, with confirmed ORR of 43.5% and PSA response rate of 54.8%.Not TGA Approved. TRITON2 trial..

Changed Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. NCT02855944. Phase 3 ARIEL4 trial. NCT02855944. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5.7 months) in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation.Not TGA approved. NCT02855944. ARIEL4. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5·7 months), including both platinum sensitive and resistant populations..

Changed GV1001 + Gemcitabine + Capecitabine in Pancreatic adenocarcinoma with CCL11 Serum level high: 2

Comments changed: Phase 3. NCT02854072. N=148. GV1001 + gemcitabine/capecitabine improved OS (11.3 vs 7.5 months) and TTP (7.3 vs 4.5 months) in eotaxin-high patients with advanced PDAC.Phase 3. NCT02854072. N=148, GV1001 + gemcitabine/capecitabine improved OS (11.3 vs 7.5 months) and TTP (7.3 vs 4.5 months) in eotaxin-high patients with advanced PDAC..

Changed Dacomitinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 2

Comments changed: Not TGA approved. Phase 3 ARCHER 1050 and 1009 trials. Dacomitinib showed improved PFS over gefitinib (14.7 vs 9.2 months) in first-line EGFR-mutation-positive NSCLC, but not over erlotinib in previously treated NSCLC (2.6 months in both groups).Not TGA approved. ARCHER 1009/1050.

Changed Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR G719, L861Q, S768I: 2

Comments changed: Intermediate response to first generation EGFR TKI; G719X mutation in NSCLC has an average response rate of 35.1% to TKIs, and other uncommon EGFR mutations such as exon 18 indels, exon 19 insertions, A763_Y764insFQEA, S768I, L861Q, kinase domain duplications, and rearrangements are also responsive to EGFR TKIs.Intermediate response to 1G TKI with resistance data.

Changed Fedratinib in Myelofibrosis with JAK2 V617F: 2

Comments changed: Not TGA approved. FDA approved. Phase 2, JAKARTA-2, NCT01523171, N=97, Fedratinib achieved a spleen response in 55% (46/83) of assessable patients with ruxolitinib-resistant or ruxolitinib-intolerant myelofibrosis, with common grade 3-4 adverse events including anaemia (38%) and thrombocytopenia (22%)..

Changed Entrectinib, Ceritinib in Solid tumours with ALK Oncogenic mutations: 4

Comments changed: Case report of a 57-year-old male patient with ALK-rearranged inflammatory myofibroblastic tumor showing drastic responses to two ALK inhibitors, ASP3026 and ceritinib (LDK378), with serum hyaluronan levels used to monitor treatment efficacy..

Changed BAY2010112 in Prostate cancer with PSMA Protein expression: 4

Comments changed: Preclinical studies. Bispecific antibodies and Fab conjugates targeting PSMA and CD3 demonstrated potent and selective activity against prostate cancer cell lines, with effective T cell redirection and cytotoxicity, and induced regression of human prostate cancer xenografts in mice..

Changed Bispecific PSMA/CD3 antibody in Prostate cancer with PSMA Protein expression: 4

Comments changed: Preclinical study. A PSMA-targeting CD3 bispecific antibody induced antitumor responses that were enhanced by 4-1BB costimulation, leading to durable antitumor responses and T-cell memory in preclinical solid tumor models..

Changed Sonidegib, Vismodegib in Medulloblastoma with PTCH1 Loss-of-function mutations: 4

Comments changed: Preclinical study. RAS/MAPK activation drives resistance to Smo inhibition and enhances metastatic behavior in Shh pathway-dependent tumors, with evidence of RAS/MAPK-driven tumor evolution in Smo inhibitor-treated BCC patients..

Changed KSQ-4279 + Olaparib in Ovarian cancer with RAD51D : 4

Alterations changed: Oncogenic mutations.

Changed A947 in Solid tumours with SMARCA4 : 4

Alterations changed: Oncogenic mutations.

Changed PRT3789 in Solid tumours with SMARCA4 : 4

Alterations changed: Oncogenic mutations.

Changed PRT3789 in Solid tumours with SMARCA4 : 4

Alterations changed: Oncogenic mutations.

Changed PRT7732 in Solid tumours with SMARCA4 : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Breast cancer with CHEK2 Oncogenic mutations: R2

Comments changed: Phase 2 TBCRC 048 study. NCT not specified. N=54. Olaparib showed ORR of 33% and 31% in cohorts 1 and 2 respectively, with responses primarily observed in gPALB2 (ORR 82%) and sBRCA1/2 (ORR 50%) mutations, but not in ATM or CHEK2 mutations alone.TBCRC048.

Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-small cell lung cancer with EGFR+RET EGFR:Oncogenic mutations and RET:fusion: R2

Comments changed: RET fusions mediate acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC, and combined EGFR and RET inhibition with osimertinib and BLU-667 shows promise as a well-tolerated and effective treatment strategy..

Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-small cell lung cancer with EGFR+ROS1 : R2

Alterations changed: EGFR:Oncogenic mutations and ROS1:fusion, GOPC-ROS1 fusion. Comments changed: Case report. GOPC-ROS1 rearrangement identified as an acquired resistance mechanism to osimertinib, with subsequent response to crizotinib combined treatments in lung adenocarcinoma patient..

Changed Ribociclib in Breast cancer with SPEN : R2

Alterations changed: Oncogenic mutations.

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-small cell lung cancer with STK11+KRAS STK11:Oncogenic mutations AND KRAS:Oncogenic mutations: R2

Comments changed: Preclinical study and retrospective observational analysis. STK11/LKB1 mutations in KRAS-mutant lung adenocarcinoma are associated with resistance to PD-1 inhibitors, resulting in lower ORR (7.4% vs 35.7% and 28.6%) and diminished PFS and OSPre-clinical study.

Saturday, 21 June 2025 (Version: 20250621AU)

New Quizartinib in Acute myeloid leukaemia with FLT3 Internal tandem duplication: 4

Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480

New Gilteritinib in Acute myeloid leukaemia with FLT3 Internal tandem duplication, D835Y, D835V, Y842C: 4

Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480

New Foretinib in Acute myeloid leukaemia with FLT3 Internal tandem duplication, F691L, D835Y, D835V, Y842C: 4

Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480

New Palbociclib in Desmoplastic small round cell tumours with WT1 EWSR1-WT1 fusion: 4

Preclinical study. Comprehensive transcriptomic analysis reveals CDK4/6 inhibitors as potential therapeutic agents for Desmoplastic Small Round Cell Tumors by targeting the cyclin D-CDK4/6-RB axis upregulated by EWSR1-WT1, with palbociclib demonstrating reduced tumor growth in xenograft models. References: 38588409

New Gilteritinib in Acute myeloid leukaemia with FLT3 F691L: R2

Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480

New Quizartinib in Acute myeloid leukaemia with FLT3 F691L, D835Y, D835V, Y842C: R2

Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480

New Polatuzumab vedotin + Bendamustine + Rituximab in Diffuse large B-cell lymphoma with KLHL6 Protein expression: R2

Preclinical study. Genome-wide CRISPR-Cas9 screens in DLBCL cell lines revealed that CD79B glycosylation and KLHL6 determine sensitivity to Polatuzumab vedotin (Pola-V) by influencing epitope availability and CD79B protein levels, respectively. References: 38683128

New Idarubicin + Cytarabine in Acute myeloid leukaemia with U2AF1 S34F, Q157R: R2

Preclinical study. U2AF1 mutations in AML confer resistance to idarubicin and cytarabine by mis-splicing mRNA translation genes and activating the integrated stress response (ISR). Targeting this pathway with ISRIB resensitizes U2AF1 mutant cells to chemotherapy. References: 38417135

Wednesday, 18 June 2025 (Version: 20250618AU)

Changed Avapritinib in Gastrointestinal stromal tumour with PDGFRA Exon 18 mutation, D842V, D842_H845del: 2

Comments changed: Not TGA approved; FDA approved. Phase 1 NAVIGATOR trial. NCT02508532. Avapritinib showed antitumor activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumors, with an overall response rate of 88% (5 complete responses, 44 partial responses). In the first-line setting at 300 mg (RP2D), ORR was 93% (26/28) with a CBR of 100%.Not TGA approved; FDA approved. Phase 1 NAVIGATOR trial. NCT02508532. Avapritinib showed promising antitumor activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumors, with an overall response rate of 88% (5 complete responses, 44 partial responses). In the first-line setting at 300 mg (RP2D), ORR was 93% (26/28) with a CBR of 100%..

Changed Cadonilimab + Anlotinib in Non-small cell lung cancer with CD274 Protein expression: 3

Comments changed: Phase Ib/II trial. NCT04646330. N=69. Cadonilimab and anlotinib demonstrated manageable safety and activity with an ORR of 51% (25/49) at 15mg/kg Q3W and 60% (12/20) at 10mg/kg Q3W as first-line treatment in advanced NSCLC. ORRs differed between PD-L1-positive (60.5%) and PD-L1-negative (42.3%) patients. PD-L1 expression was assessed by immunohistochemistry using PD-L1 IHC 22C3 pharmDx (Dako Omnis), with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%. High PD-L1 expression was not required for entry into the trial.Phase Ib/II trial. NCT04646330. N=69. Cadonilimab and anlotinib demonstrated manageable safety and promising efficacy with an ORR of 51% (25/49) at 15mg/kg Q3W and 60% (12/20) at 10mg/kg Q3W as first-line treatment in advanced NSCLC. ORRs differed between PD-L1-positive (60.5%) and PD-L1-negative (42.3%) patients. PD-L1 expression was assessed by immunohistochemistry using PD-L1 IHC 22C3 pharmDx (Dako Omnis), with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%. High PD-L1 expression was not required for entry into the trial..

Changed Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3

Comments changed: Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma..

Changed Izalontamab brengitecan in Non-small cell lung cancer with EGFR Oncogenic mutation and NOT Exon 19 deletion and NOT L858R, Exon 20 insertion: 3

Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 69% and mPFS of 7.0 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 69% and mPFS of 7.0 months..

Changed Izalontamab brengitecan in Non-small cell lung cancer with ERBB2 Oncogenic mutations: 3

Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 53%, DCR 100%, and mPFS of 7.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 53%, DCR 100%, and mPFS of 7.5 months..

Changed TQB2102 in Colorectal adenocarcinoma with ERBB2 Overexpression: 3

Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%).

Changed TQB2102 in Gastric cancer with ERBB2 Overexpression: 3

Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%).

Changed TQB2102 in Solid tumours with ERBB2 Overexpression: 3

Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%).

Changed TQB2102 in Breast cancer with ERBB2 Overexpression, Protein expression, Low-protein expression: 3

Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%).

Changed Sotorasib + Panitumumab in Colorectal adenocarcinoma with KRAS G12C: 3

Comments changed: Phase 1b CodeBreaK 101 trial. NCT04185883. N=40. Sotorasib + panitumumab + FOLFIRI showed efficacy in pretreated KRAS G12C-mutated mCRC with ORR of 57.5%, median PFS of 8.2 months, and median OS of 17.9 months.Phase 1b CodeBreaK 101 trial. NCT04185883. N=40. Sotorasib + panitumumab + FOLFIRI showed promising efficacy in pretreated KRAS G12C-mutated mCRC with ORR of 57.5%, median PFS of 8.2 months, and median OS of 17.9 months..

Changed Izalontamab brengitecan in Non-small cell lung cancer with KRAS Oncogenic mutations, G12C: 3

Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months..

Changed Izalontamab brengitecan in Non-small cell lung cancer with MET Exon 14 deletion, Exon 14 splicing mutation,: 3

Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months..

Changed SHR-1826 in Solid tumours with MET Overexpression, Amplification, Oncogenic mutation: 3

Comments changed: Phase 1 study. NCT06094556. N=116. SHR-1826, a c-MET-directed antibody-drug-conjugate, demonstrated a manageable safety profile and anti-cancer activity in heavily pretreated advanced solid tumors, particularly in NSCLC patients with an ORR of 40% and median PFS of 6.8 months.Phase 1 study. NCT06094556. N=116. SHR-1826, a c-MET-directed antibody-drug-conjugate, demonstrated a manageable safety profile and promising anti-cancer activity in heavily pretreated advanced solid tumors, particularly in NSCLC patients with an ORR of 40% and median PFS of 6.8 months..

Changed Izalontamab brengitecan in Non-small cell lung cancer with ALK Fusion: 4

Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months..

Changed Exarafenib in Solid tumour with BRAF V600E, Class II mutations, Class III mutations: 4

Comments changed: Phase 1/1b trial. NCT04913285. Exarafenib demonstrated clinical activity and tolerability in patients with BRAF-altered solid tumors and NRAS mutant melanoma, with a ORR 18% and SD in 47% of patients.Phase 1/1b trial. NCT04913285. Exarafenib demonstrated promising clinical activity and tolerability in patients with BRAF-altered solid tumors and NRAS mutant melanoma, with a ORR 18% and SD in 47% of patients..

Changed Tusamitamab ravtansine in Non-small cell lung cancer with CEACAM5 Overexpression: 4

Comments changed: Phase1/2 trial. NCT02187848. SAR408701, an antibody-drug conjugate, showed antitumor activity in heavily pretreated NSQ NSCLC patients with high CEACAM5 expression, with an ORR of 20%.Phase1/2 trial. NCT02187848. SAR408701, an antibody-drug conjugate, showed promising antitumor activity in heavily pretreated NSQ NSCLC patients with high CEACAM5 expression, with an ORR of 20%..

Changed BNT142 in Ovarian cancer, Solid tumours with CLDN6 Protein expression: 4

Comments changed: Phase 1/2 BNT142-01 trial. NCT05262530. N=65. BNT142 showed anti-tumor activity with 7 partial responses in ovarian cancer and a disease control rate of 58% across all dose levels in CLDN6+ advanced solid tumors. CLDN6 positivity is defined as ≥ membrane positivity in 10% of cell. No clear relationship beween CLDN6 expression level versus response seen.Phase 1/2 BNT142-01 trial. NCT05262530. N=65. BNT142 showed promising anti-tumor activity with 7 partial responses in ovarian cancer and a disease control rate of 58% across all dose levels in CLDN6+ advanced solid tumors. CLDN6 positivity is defined as ≥ membrane positivity in 10% of cell. No clear relationship beween CLDN6 expression level versus response seen..

Changed GQ1001 in Solid tumour with ERBB2 Overexpression, Amplification: 4

Comments changed: Phase Ia study. NCT04450732. GQ1001, a HER2-targeting ADC, showed antitumor activity in HER2-positive advanced solid tumors, with 6 out of 15 evaluable subjects achieving confirmed partial response at doses ≥ 7.2 mg/kg, and a median progression-free survival of 4.8 months.Phase Ia study. NCT04450732. GQ1001, a HER2-targeting ADC, showed promising antitumor activity in HER2-positive advanced solid tumors, with 6 out of 15 evaluable subjects achieving confirmed partial response at doses ≥ 7.2 mg/kg, and a median progression-free survival of 4.8 months..

Changed D3S-001 in Non-small cell lung cancer with KRAS G12C: 4

Comments changed: Preclinical study. D3S-001, a GDP-bound KRAS G12C inhibitor with rapid target engagement kinetics, showed robust antitumor activity preclinically and clinical efficacy.Preclinical study. D3S-001, a GDP-bound KRAS G12C inhibitor with rapid target engagement kinetics, showed robust antitumor activity preclinically and promising clinical efficacy..

Changed Izalontamab brengitecan in Non-small cell lung cancer with RET Fusion: 4

Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months..

Changed Izalontamab brengitecan in Non-small cell lung cancer with ROS1 Fusion: 4

Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months..

Changed Zolbetuximab, Zolbetuximab + Pembrolizumab in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: R2

Comments changed: Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma..

Changed Durvalumab in Endometrial cancer with Mismatch repair Proficient, NOT Deficient: R2

Comments changed: Phase 2 trial. NCT03015129. Durvalumab showed activity in dMMR advanced endometrial carcinoma with ORR of 47% and median PFS of 8.3 months, but limited activity in pMMR advanced endometrial carcinoma with ORR of 3% and median PFS of 1.8 months.Phase 2 trial. NCT03015129. Durvalumab showed promising activity in dMMR advanced endometrial carcinoma with ORR of 47% and median PFS of 8.3 months, but limited activity in pMMR advanced endometrial carcinoma with ORR of 3% and median PFS of 1.8 months..

Monday, 16 June 2025 (Version: 20250616AU)

New Varegacestat in Aggressive fibromatosis with APC Loss-of-function mutations; oncogenic mutations: 3

Phase 2 RINGSIDE trial. NCT04871282. Varegacestat showed an Objective Response Rate (ORR) of 64% and Disease Control Rate (DCR) of 97% in patients with desmoid tumors, with a median best change in tumor volume of -85% and a well-tolerated safety profile at the recommended 1.2 mg QD dose. Responses were seen in both PC (43%, n=7) and CTNNB1 (68%, n=19) mutations. References: 10.1016/j.annonc.2024.08.1857, 10.1200/JCO.2025.43.16_suppl.11516

New Varegacestat in Aggressive fibromatosis with CTNNB1 T41A, S45F, Gain-of-function mutations, Oncogenic mutations: 3

Phase 2 RINGSIDE trial. NCT04871282. Varegacestat showed an Objective Response Rate (ORR) of 64% and Disease Control Rate (DCR) of 97% in patients with desmoid tumors, with a median best change in tumor volume of -85% and a well-tolerated safety profile at the recommended 1.2 mg QD dose. Responses were seen in both APC (43%, n=7) and CTNNB1 (68%, n=19) mutations. References: 10.1016/j.annonc.2024.08.1857, 10.1200/JCO.2025.43.16_suppl.11516

New LOXO-783, LOXO-783 + Fulvestrant, LOXO-783 + Letrozole, LOXO-783 + Anaztrozole, LOXO-783 + Paclitaxel in Solid tumours with PIK3CA H1047R: R2

Phase 1a/b PIKASSO-01 trial. NCT05307705. LOXO-783, a PI3Kα H1047R inhibitor, demonstrated mutant selectivity and reduced hyperglycemia, with objective response rates (ORR) and clinical benefit rates (CBR) of 3%/17% in monotherapy, 5%/19% with endocrine therapy, and 19%/25% when combined with paclitaxel, though limited by high rates of diarrhea. References: 10.1158/1557-3265.SABCS24-PS7-03

Removed LOXO-783 in Solid tumours with PIK3CA alterations H1047R: Tier 4

Changed Brentuximab Vedotin in Anaplastic large cell lymphoma with CD30 Protein expression: 1

Comments changed: PBS reimbursed. Phase 2 trial. N=58. Brentuximab vedotin induced objective responses in 86% of patients and CRs in 57% with relapsed/refractory systemic ALCL, with median duration of response of 12.6 months, targeting CD30-positive malignant cells..

Changed Brentuximab Vedotin in Cutaneous T-cell lymphoma with CD30 Protein expression: 1

Comments changed: PBS reimbursed. Phase 3 ALCANZA trial. NCT01578499. N=128. Brentuximab vedotin significantly improved objective global response lasting at least 4 months compared to physician's choice (56.3% vs 12.5%) in CD30-positive cutaneous T-cell lymphoma patients..

Changed Daratumumab + Bortezomib + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1

Comments changed: Phase 3 trial. NCT02136134. N=498. Daratumumab + bortezomib + dexamethasone significantly improved PFS (HR, 0.39) and ORR (82.9% vs 63.2%) compared to bortezomib + dexamethasone in relapsed or refractory multiple myeloma, with higher CD38 expression associated with better response..

Changed Goserelin in Breast cancer with ESR1 Protein expression: 1

Comments changed: Standard of care. Randomised clinical trial. N=138 (136 eligible). Goserelin resulted in similar FFS and OS as surgical ovariectomy in premenopausal patients with ER and/or PgR-positive metastatic breast cancer..

Changed Medroxyprogesterone Acetate in Breast cancer with ESR1 Protein expression: 1

Comments changed: Standard of care. Randomised phase 3 trials compared the efficacy of megestrol acetate or medroxyprogesterone acetate with tamoxifen in postmenopausal women with advanced breast cancer, showing similar response rates (25-44% vs 31-35%) and median survival times (20-24 months vs 26-32 months), with some subgroup differences in response..

Changed Tamoxifen in Breast cancer with ESR1 Protein expression: 1

Comments changed: Standard of care. Tamoxifen showed a 32% response rate in 59 postmenopausal women with advanced breast cancer, with tumors containing estrogen receptors and those responding to previous hormonal manipulation more likely to respond (60% and 69%, respectively)..

Saturday, 14 June 2025 (Version: 20250614AU)

New Ceritinib in Non-small cell lung cancer with ALK Amplification: 4

Retrospective study. ALK-positive NSCLC. Median PFS on sequential crizotinib and ceritinib was 17.4 months, with ceritinib showing significant antitumor activity even after crizotinib treatment, and no difference in PFS on ceritinib between patients with or without ALK resistance mutations. Updated 2025-06-14. References: 25724526

New Avapritinib in Solid tumours with KIT D816V, V654A, N655K, Y672C, D677N, T670A: 4

Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation. References: 31270078

New Crizotinib in Non-small cell lung cancer with ALK C1156Y, Fusion and Amplification, L1196M, S1206Y, G1269A, T1151ins: R2

Retrospective study. ALK-positive NSCLC. Median PFS on sequential crizotinib and ceritinib was 17.4 months, with ceritinib showing significant antitumor activity even after crizotinib treatment, and no difference in PFS on ceritinib between patients with or without ALK resistance mutations. Updated 2025-06-14. References: 25724526

New Crizotinib in Non-small cell lung cancer with ALK Fusion AND Amplification, L1196M, C1156Y, F1174L, F1174V, G1202R, G1269A, I1171T, I1171S, L1152R, L1152V, T1151R, T1151M, L1198F, S1206F, D1203E: R2

Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085

New Ensartinib in Non-small cell lung cancer with EGFR Oncogenic mutations: R2

Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085

New Ensartinib in Non-small cell lung cancer with ERBB2 Oncogenic mutations: R2

Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085

New Avapritinib in Solid tumours with KIT V560D, V560D and V654A, V560D and and V670I, T670I, T670V: R2

Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation. References: 31270078

New Ensartinib in Non-small cell lung cancer with KRAS Oncogenic mutations: R2

Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085

Changed Selpercatinib in Medullary thyroid cancer with RET : 2

Alterations changed: Oncogenic mutations, M918TOncogenic mutation, M918T.

Changed Olaparib + Durvalumab in Solid tumours with BRCA2 : 3

Alterations changed: Oncogenic mutations.

Changed Olaparib, Talazoparib, Niraparib, Rucaparib in Uterine leiomyosarcoma with BRCA2 : 3

Alterations changed: Oncogenic mutations, DeletionsOncogenic mutation, Deletion.

Changed Cabozantinib in Gastrointestinal stromal tumour with KIT : 3

Alterations changed: Protein expression, Oncogenic mutations, Exon 9 mutation, Exon 11 mutationProtein expression, Oncogenic mutation, Exon 9 mutation, Exon 11 mutation.

Changed Izalontamab brengitecan in Non-small cell lung cancer with KRAS : 3

Alterations changed: Oncogenic mutations, G12COncogenic mutation, G12C.

Changed Ensartinib in Non-small cell lung cancer with ALK : 4

Alterations changed: Fusion AND Amplification, L1196M, C1156Y, F1174L, F1174V, G1202R, G1269A, I1171T, I1171S, L1152R, L1152V, T1151R, T1151M, L1198F, S1206F, D1203EAmplification, protein expression. Comments changed: Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14.. References changed: 31628085, 25724526.

Changed Therapy in Solid tumours with BRAF Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R: 4

Therapy changed: Vociprotafib + CobimetinibRMC-4630 + Cobimetinib.

Changed KSQ-4279 + Olaparib in Ovarian cancer with BRCA1 : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib + Durvalumab in Solid tumours with BRCA1 : 4

Alterations changed: Oncogenic mutations.

Changed Tuvusertib in Solid tumours with BRCA1 : 4

Alterations changed: Oncogenic mutations.

Changed ABBV-637 + Osimertinib in Non-small cell lung cancer with EGFR : 4

Alterations changed: Oncogenic mutations.

Changed GB263T in Non-small cell lung cancer with EGFR : 4

Alterations changed: Oncogenic mutations, Exon 20 insertion, C797SOncogenic mutation, Exon 20 insertion, C797S.

Changed Midostaurin in Solid tumours with KIT D816V, T670A, T670V: 4

Comments changed: Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation..

Changed Sorafenib in Thymic carcinoma with KIT : 4

Alterations changed: Exon 11 mutation, Exon 11 deletion. Comments changed: Case report. A relapsed thymic carcinoma patient with C-KIT exon 11 deletion mutation showed positive response to sorafenib..

Changed Bezuclastinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation, Exon 11 deletion, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829P: 4

Comments changed: Phase 1b/2a trial. NCT02401815. N=39. Combination of type I KIT inhibitor PLX9486 and type II KIT inhibitor sunitinib showed clinical benefit in patients with refractory GIST, with median PFS of 12.1 months and clinical benefit rate of 80% at the recommended phase 2 dose..

Changed Therapy in Thymic carcinoma with KIT Exon 11 mutation, Exon 11 deletion, V560del: 4

Therapy changed: ImatinibSorafenib. Comments changed: Case report. Thymic carcinoma with overexpressed mutated KIT showed response to imatinib..

Changed Imatinib in Thymic carcinoma with KIT Exon 11 mutation, Y553N: 4

Comments changed: Case report. A heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma showed an impressive response to imatinib..

Changed Sorafenib in Thymic carcinoma with KIT Exon 17 mutation, D820E: 4

Comments changed: Case report. A heavily pretreated patient with metastatic thymic carcinoma responded to sorafenib, with a c-kit missense mutation (D820E) on exon 17 potentially explaining the clinical response..

Changed Cabozantinib in Gastrointestinal stromal tumour with KIT : 4

Alterations changed: Exon 9 mutations, A502_Y503dup, Exon 11 mutations, Exon 11 deletion, K558_G565delinsR, Exon 17 mutations, D820G, V559A, V559D, V560G, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829PExon 9 mutations, A502_Y503dup, Exon 11 mutations, K558_G565delinsR, Exon 17 mutations, D820G.

Changed Axitinib in Gastrointestinal stromal tumour with KIT L576P, V669D, V559A, V559G, T670I, V654A, N822K, A829P: 4

Comments changed: Preclinical study. Axitinib showed potent activity against various cKIT primary and secondary mutations, including imatinib-resistant T670I and V654A mutants, in GIST preclinical models and patient-derived primary cells..

Changed LOP628 in Solid tumours with KIT Overexpression: 4

Comments changed: Preclinical study. c-KIT-directed antibody-drug conjugate LOP628 exhibited potent antiproliferative activity against c-KIT-positive cell lines and demonstrated regressions or stasis in GIST and SCLC xenograft models, including an imatinib-resistant GIST model..

Changed Therapy in Solid tumours with KRAS Amplification: 4

Therapy changed: VociprotafibSAR442720.

Changed Therapy in Solid tumours with KRAS G12: 4

Therapy changed: AvutometinibCH5126766. Comments changed: Phase 1 dose-escalation and basket dose-expansion study. NCT02407509. Avutometinib, a RAF-MEK inhibitor, demonstrated antitumour activity in RAS/RAF-mutant solid tumours and multiple myeloma, with 7 (27%) of 26 response-evaluable patients achieving objective responses at the recommended phase 2 dose of 4.0 mg twice per week..

Changed Therapy in Solid tumours with KRAS G12, Amplification: 4

Therapy changed: Vociprotafib + CobimetinibRMC-4630 + Cobimetinib.

Changed Therapy in Solid tumours with NF1 Oncogenic mutations: 4

Therapy changed: Vociprotafib + CobimetinibRMC-4630 + Cobimetinib.

Changed VT104 in Mesothelioma with NF2 : 4

Alterations changed: Oncogenic mutations, DeletionOncogenic mutation, Deletion.

Changed Ipatasertib, MK-2206 in Prostate cancer with PIK3R1 : 4

Alterations changed: Oncogenic mutations, DeletionOncogenic mutation, Deletion.

Changed Regorafenib in Solid tumours with BRAF : R2

Alterations changed: Oncogenic mutations, Amplification, Fusion, Class I mutation, Class II mutation, Class III mutation, BCAP29-BRAF fusion, SND1-BRAF fusion, D594G, D594N, G466A, G469A, G469R, G469V, G596C, I617V, K601E, N486_P490del, N581I, V487_P492>A, V600E, V600E , V600KOncogenic mutation, Amplification, Fusion, Class I mutation, Class II mutation, Class III mutation, BCAP29-BRAF fusion, SND1-BRAF fusion, D594G, D594N, G466A, G469A, G469R, G469V, G596C, I617V, K601E, N486_P490del, N581I, V487_P492>A, V600E, V600E , V600K.

Changed Therapy in Colorectal adenocarcinoma with ERBB2 ERBB2-GRB7 fusion: R2

Therapy changed: Afatinib, Trastuzumab, Cetuximab, Cetuximab + irinotecan. Comments changed: Case series. Targetable kinase alterations (RTK alterations and MAP2K1 mutations) identified in 8% of colorectal carcinoma, preferentially associated with wild-type RAS/RAF, and may predict poor response to anti-EGFR therapy..

Changed Afatinib, Dacomitinib, Neratinib, Pyrotinib in Solid tumours, Non-small cell lung cancer with ERBB2 Exon 20 insertion except G778ins, S779ins, P780ins: R2

Comments changed: Preclinical study. ERBB2 mutations characterized across 25 tumor types, with poziotinib showing potent activity against HER2 mutants, and enhancing T-DM1 activity in pre-clinical models, and showing 42% confirmed objective response rate in ERBB2 exon 20-mutant NSCLC patients..

Changed Lapatinib in Solid tumours with ERBB2 L755S, L755P, A775_G776insYVMA (Y772_A775dup), G778ins, P780_Y781insGSP (G778_P780dup), P780ins, V842I, L869R: R2

Comments changed: Preclinical study. ERBB2 mutations characterized across 25 tumor types, with poziotinib showing potent activity against HER2 mutants, and enhancing T-DM1 activity in preclinical models, with a 42% confirmed objective response rate in ERBB2 exon 20-mutant NSCLC patients in Phase 2 clinical testing..

Changed Midostaurin with KIT : R2

Cancer type(s) changed: Solid tumoursGastrointestinal stromal tumour Alterations changed: V654A, N655K, Y627C, D677N, T670I, T670A, T670VV654A, T670I. Comments changed: Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation.Preclinical study. ATP-competitive inhibitors midostaurin and avapritinib displayed distinct resistance profiles in exon 17-mutant KIT, with avapritinib being selectively problematic for T670I gatekeeper mutation, conferring resistance indirectly through conformational changes..

Changed Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with PTEN : R2

Alterations changed: Oncogenic mutations, DeletionOncogenic mutation, Deletion.

Friday, 13 June 2025 (Version: 20250613AU)

New Brigatinib in Non-small cell lung cancer with ROS1 Fusions: 3

Phase 2. Barossa study. N=51. Brigatinib showed an ORR of 71% and median PFS of 12.0 months in TKI-naive NSCLC patients, and 32% ORR with 7.3 months median PFS in crizotinib-pretreated NSCLC patients. References: 39018589

New Azenosertib in Solid tumours with CCNE1 Amplification: 4

Preclinical study. Azenosertib demonstrated broad antitumor activity across solid tumors in Phase I monotherapy studies. Preclinical data revealed tumor growth inhibition >60% in CCNE1-amplified models (2/2) and FBXW7-mutated models (3/5). References: 34423975

New Azenosertib in Solid tumours with FBXW7 Oncogenic mutations: 4

Preclinical study. Azenosertib demonstrated broad antitumor activity across solid tumors in Phase I monotherapy studies. Preclinical data revealed tumor growth inhibition >60% in CCNE1-amplified models (2/2) and FBXW7-mutated models (3/5). References: 34423975

New Paclitaxel in Oesophageal squamous cell carcinoma with LGALS1 Protein expression: R2

Preclinical study. Galectin-1 is a key mediator of paclitaxel resistance in esophageal squamous cell carcinoma, acting through the interaction with β-catenin and enhancing MDR1 transcription, thereby increasing resistance to paclitaxel. References: 39186691

Removed Palbociclib in Triple-negative breast cancer with CDKN2A alterations Oncogenic mutations: Tier R2

Changed Obinutuzumab in Follicular lymphoma with CD20 Protein expression: 1

Comments changed: Phase 3 trial. TOWER. NCT02013167. N=405. Blinatumomab significantly improved overall survival (7.7 vs 4.0 months), remission rates (44% vs 25%), and event-free survival (31% vs 12%) in adults with relapsed or refractory B-cell precursor ALL, including both Ph-positive and Ph-negative subtypes. Note that surface antigen CD-19 is lineage-specific to B-cells and constitutively expressed on the majority of B-cell precursor ALL blasts and does not represent a biomarker selection criteria.PBS reimbursed.

Changed Gemtuzumab Ozogamicin in Acute myeloid leukaemia with CD33 Protein expression: 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3 AAML0531 trial (N=1022) demonstrated that gemtuzumab ozogamicin, a CD33-targeted immunoconjugate, added to chemotherapy improved event-free survival (53.1% vs 46.9%) by reducing relapse risk (32.8% vs 41.3%) in children and adolescents with de novo acute myeloid leukemia..

Changed Daratumumab + Hyaluronidase-fihj in Multiple myeloma with CD38 Overexpression: 2

Comments changed: Phase 3 COLUMBA trial. NCT03277105. Subcutaneous daratumumab was non-inferior to intravenous daratumumab in terms of overall response (41% vs 37%)..

Changed BOS172738 in Medullary thyroid cancer with RET Fusions: 3

Comments changed: Phase 1 study. NCT03780517. BOS172738, a potent and selective RET inhibitor, showed an ORR of 33% in RET-altered tumors, including 33% in NSCLC and 44% in MTC (7/16, including 1 CR), with a favorable safety profile and durable responses.ORR 44% (7/16), including 1 CR.

Changed Vandetanib in Non-small cell lung cancer with RET Fusions: 3

Comments changed: Phase 2 LURET trial. UMIN000010095. Vandetanib showed an ORR of 53% (9/17) and median PFS of 4.7 months in patients with RET-rearranged advanced NSCLC, indicating RET rearrangement as a targetable alteration.Single-arm phase 2. LURET. ORR 47%. PFS 4.7mo. References changed: 2782561627825636.

Changed Cabozantinib in Non-small cell lung cancer with RET : 3

Alterations changed: Fusions, KIF5B-RET fusion, Rearrangement. Comments changed: Phase 2 trial. NCT01639508. N=26. Cabozantinib yielded an ORR of 28% in patients with RET-rearranged non-small-cell lung cancer, with KIF5B-RET being the predominant fusion type.Not TGA approved. Single-arm phase 2. ORR 28%.

Changed Cabozantinib in Non-small cell lung cancer with ROS1 Fusions: 4

Comments changed: Case report. Cabozantinib showed effectiveness in treating a CD74-ROS1-positive advanced NSCLC patient for 1.5 years, and subsequent crizotinib therapy remained effective after cabozantinib resistance developed.. References changed: 32103985, NCT01639508.

Changed Tazemetostat in Ovarian small cell carcinoma with SMARCA2 Loss-of-function mutations: 4

Comments changed: Preclinical study. Xenograft and cell line SCCOHT models deficient in SMARCA2 and SMARCA4 showed antiproliferative and antitumour effects when treated with EZH2 inhibitor tazemetostat, exemplifying an additional class of rhabdoid-like tumours dependent on EZH2 activity for survival.Xenograft and cell line SCCOHT models. Induces potent antiproliferative and antitumour effects..

Changed Palbociclib in Non-small cell lung cancer with SMARCA4 Loss-of-function mutations: 4

Comments changed: Preclinical study. SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in NSCLC, due to reduced cyclin D1 expression caused by restricted CCND1 chromatin accessibility and suppressed c-Jun, a transcription activator of CCND1.SMARCA4 loss is synthetic lethal with palbociclib in NSCLC cell line..

Changed Pembrolizumab in SMARCA4-deficient thoracic sarcoma with SMARCA4 Oncogenic mutations: 4

Comments changed: Case report. Exceptional response to pembrolizumab observed in a SMARCA4-deficient thoracic sarcoma overexpressing PD-L1, suggesting pembrolizumab as a potential treatment strategy for PD-L1-positive SMARCA4-DTS..

Changed BET inhibitor in Solid tumours with SMARCA4 Oncogenic mutations: 4

Comments changed: Preclinical study. Bromodomains are acetyl lysine 'reader' modules with potential anticancer activities, and BET inhibitor programmes provide insights for developing non-BET bromodomain-targeting drugs..

Changed Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with SMARCB1 Oncogenic mutations: 4

Comments changed: Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status, with median PFS and OS of 9 and 15 months, respectively, and 2 patients having ongoing responses at 33+ and 36+ months.Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status..

Changed Itraconazole, Arsenic trioxide in Basal cell carcinoma, Medulloblastoma with SMO D477G, E522K, G457S, S391N, D388N, N223D, L225R: 4

Comments changed: Preclinical study. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation, showing activity against tumors with acquired resistance to Smoothened antagonists, including SMO(D477G) mutant.Preclinical study. Itraconazole and arsenic trioxide block resistant SMO mutation activity in vitro..

Changed Posaconazole in Basal cell carcinoma with SMO Oncogenic mutations: 4

Comments changed: Preclinical study. Posaconazole inhibits Hedgehog signaling pathway by antagonizing Smoothened (SMO) with a distinct mechanism, showing robust activity against drug-resistant SMO mutants and inhibiting Hh-dependent basal cell carcinoma growth in vivo.Cell-line evidence only.

Changed JQ1 in Solid tumours with SMO Oncogenic mutations: 4

Comments changed: Preclinical study. BET bromodomain inhibition through JQ1 effectively targets Hedgehog-driven tumors, including those with genetic lesions conferring resistance to Smoothened antagonists, by directly regulating GLI transcription..

Changed Everolimus in Perivascular epithelioid cell tumour with TSC1 Oncogenic mutations: 4

Comments changed: Phase 3 EXIST-2 trial. NCT00790400. Everolimus showed significant angiomyolipoma response rate of 42% (50% reduction in total volume) compared to 0% with placebo in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis..

Changed Everolimus in Renal cell carcinoma with TSC1 Oncogenic mutations: 4

Comments changed: Mutations in MTOR, TSC1, or TSC2 were more common in responders (28%) than nonresponders (11%) to rapalogs in metastatic renal cell carcinoma, indicating a potential association between mTOR pathway gene mutations and treatment response.Drug is PBS reimbursed but not biomarker selected.

Changed Everolimus in Perivascular epithelioid cell tumour with TSC2 Oncogenic mutations: 4

Comments changed: Phase 3 EXIST-2 trial. NCT00790400. Everolimus showed significant angiomyolipoma response rate of 42% (50% reduction in total volume) compared to 0% with placebo in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis..

Changed Everolimus in Renal cell carcinoma with TSC2 Oncogenic mutations: 4

Comments changed: Phase 2 RECORD-3 study. NCT00903175. No significant difference in OS between first-line everolimus followed by sunitinib and first-line sunitinib followed by everolimus in metastatic RCC.No survival benefit vs Sunitinib.

Changed Pembrolizumab in Colorectal adenocarcinoma with Tumour Mutational Burden High: 4

Comments changed: Phase 2 KEYNOTE-158 study. NCT02628067. Prospective biomarker analysis in 790 patients showed tTMB-high status (>=10 mutations per megabase) was associated with improved ORR to pembrolizumab (29% vs 6% in non-tTMB-high). However, tTMB could be a novel predictive biomarker for response to pembrolizumab in patients with advanced solid tumours, KEYNOTE-158 did not include MSS colorectal cancers..

Changed Toripalimab in Gastric cancer with Tumour Mutational Burden High: 4

Comments changed: Phase Ib/2 NCT02915432 trial. Toripalimab demonstrated an overall response rate of 12.1% and median overall survival of 4.8 months in chemo-refractory gastric cancer. The TMB-high group exhibited significantly superior overall survival of 14.6 months compared to 4.0 months, with an objective response rate of 33% versus 6% in the low TMB group at the 12 mutations/MB threshold.Exploratory analysis showed ORR 33 v 6% at TMB threshold of 12/MB.

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, immune checkpoint blockade,PD-1 targeting, immune checkpoint blockade,PD-L1 targeting in Solid tumours with Tumour Mutational Burden High: 4

Comments changed: Pan-cancer analysis of 1,662 patients treated with immune checkpoint inhibitors (ICI) showed higher tumor mutational burden (TMB) associated with improved overall survival across multiple cancer types, although TMB cutpoints varied between cancer types..

Changed Olaparib in Breast cancer with XRCC2 Loss-of-function mutations: 4

Comments changed: Preclinical study. Synthetic lethal screening in MCF7 cells identified sensitivity to PARG inhibitor PDD00017273 in DNA damage-response deficient cells with BRCA1, BRCA2, PALB2, FAM175A, and BARD1 deficiencies, suggesting potential for single treatment therapy in HR deficient tumours.Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273.

Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab in Colorectal adenocarcinoma with KRAS Oncogenic mutations: R1

Comments changed: RAS mutations, including KRAS and NRAS, were associated with resistance to anti-EGFR therapy, with patients having RAS wild-type tumors showing improved PFS and OS when treated with panitumumab-FOLFOX4 or cetuximab..

Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab in Colorectal adenocarcinoma with NRAS Oncogenic mutations: R1

Comments changed: RAS mutations, including KRAS and NRAS, were associated with resistance to anti-EGFR therapy, with patients having RAS wild-type tumors showing improved PFS and OS when treated with panitumumab-FOLFOX4 or cetuximab..

Changed Larotrectinib in Solid tumours with NTRK1 F589L, A608D, G595R, G667C, G667S: R1

Comments changed: Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.. References changed: 10.1158/1538-7445.AM2016-LB-11830333516.

Changed Entrectinib in Solid tumours with NTRK1 G595R, G667C: R1

Comments changed: Blacklisted by FDA approval. Review discussing NTRK fusion-positive cancers, detection methods, and treatment with TRK inhibitors, highlighting resistance mediated by NTRK kinase domain mutations and potential overcoming by second-generation TRK inhibitors..

Changed Larotrectinib in Solid tumours with NTRK2 Q596E, Q596P, G623S, F633L: R1

Comments changed: Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101..

Changed Entrectinib in Solid tumours with NTRK3 G623R: R1

Comments changed: Blacklisted by FDA approval. Review discussing NTRK fusion-positive cancers, detection methods, and treatment with TRK inhibitors, highlighting resistance mediated by NTRK kinase domain mutations and potential overcoming by second-generation TRK inhibitors..

Changed Larotrectinib in Solid tumours with NTRK3 G623R, G696A, F617L, F617L, F617C, F617I: R1

Comments changed: Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.. References changed: 10.1158/1538-7445.AM2016-LB-11830333516.

Changed LY3023414 in Endometrial cancer with AKT1 Oncogenic mutations: R2

Comments changed: Phase 2 study. NCT02684032. N=28. LY3023414 showed modest activity in patients with advanced endometrial cancer harboring PI3K pathway mutations, with ORR 16%, CBR 28%, median PFS 2.5 months, and median OS 9.2 months.N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months.

Changed Pembrolizumab, Atezolizumab, Nivolumab, Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-small cell lung cancer with ALK Fusion: R2

Comments changed: IMMUNOTARGET registry. Retrospective study. N=551. Patients with advanced NSCLC and oncogenic driver alterations treated with ICI monotherapy. Objective response rate (ORR) varied by driver alteration: ALK=0%, EGFR=12%, KRAS=26%, BRAF=24%. Median PFS=2.8 months, OS=13.3 months. Notable lack of response in ALK fusion group..

Changed Lorlatinib in Non-small cell lung cancer with ALK L1198F and C1156Y: R2

Comments changed: Targeting ALK in ALK-rearranged malignancies is limited by emergence of drug resistance, with diverse mechanisms of resistance discovered, informing development of novel therapeutic strategies to overcome resistance..

Changed Venetoclax in Chronic lymphocytic leukaemia with BCL2 G101V, D103Y, A113G: R2

Comments changed: Retrospective case reports, Novel BCL2 mutations, including G101V, were identified in venetoclax-resistant CLL patients, conferring resistance by reducing the affinity of BCL2 for venetoclax and providing a potential biomarker for impending clinical relapse..

Changed SHP099, RMC-4550 in Triple-negative breast cancer with BRAF G464V, Class II mutations: R2

Comments changed: Preclinical study. SLLIP trial. NCT03248089. N=185. BRAF alterations detected in 22 patients (12%), with 82% being non-V600 mutations, and showed varied sensitivity to SHP2 inhibition in vitro. In cell line model for Class 2 mutation showed relative resistance to SHP2 inhibitors.Cell line model for Class II mutation showed relative resistance to SHP2 inhibitors..

Changed Cetuximab, Panitumumab in Colorectal adenocarcinoma with BRAF G469A, G469V, L485F, L525R, L597R, T599_V600TinsT, K601E, Class II mutations: R2

Comments changed: Retrospective study. Class 2 BRAF mutants had lower ORR compared to Class 3 (8% vs 50%) to anti-EGFR therapy, with 0% ORR in third-and-later lines treatment.Retrospective study. ORR 0% in class II BRAF mutants in third-and-later lines treatment..

Changed Divarasib in Colorectal adenocarcinoma, Solid tumours with BRAF G469A, L597Q, L597R, V600E, K601E: R2

Comments changed: Phase 1 trial. GO42144. NCT04449874. Divarasib. Confirmed response observed in 53.4% NSCLC and 29% colorectal cancer patients with KRAS G12C mutation, with median PFS of 13.1 and 5.6 months, respectively; serial ctDNA assessment identified genomic alterations associated with response and potential acquired and treatment-emergent resistance mechanisms.Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations.

Changed Vemurafenib in Melanoma with BRAF K601E: R2

Comments changed: Case report. Lack of response to vemurafenib in melanoma carrying BRAF K601E mutation.Case report. Lack of response to melanoma.

Changed Vemurafenib in Melanoma with BRAF L505H: R2

Comments changed: Case report. Class 2 BRAF mutation. Secondary BRAF(L505H) mutation acquired following Vemurafenib treatment, contributing to resistance in metastatic BRAF mutant melanoma patients.Case report. Secondary mutation acquired following Vemurafenib..

Changed Osimertinib in Non-small cell lung cancer with BRAF Oncogenic mutations, fusion: R2

Comments changed: Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy identified EGFR T790M mutation as the most common mechanism (63%), followed by less frequent mechanisms including MET amplification (5%), HER2 amplification (13%), small cell transformation (3%), and BRAF mutations.Off-target mechanism.

Changed Palbociclib in Pancreatic adenocarcinoma, Cholangiocarcinoma, Gallbladder cancer with CDKN2A Loss-of-function mutations, Oncogenic mutations: R2

Comments changed: TAPUR Study. N=20. Palbociclib monotherapy showed no objective response or stable disease at 16 weeks in patients with pancreatic and biliary cancers with CDKN2A loss or mutation, with median PFS of 7.2 and 7.3 weeks, and median OS of 12.4 and 11.1 weeks respectively.TAPUR. N=20. ORR and DCR 0%.. References changed: 3510071410.1200/PO.19.00124.

Changed Tazemetostat in Solid tumours with SMARCA4 Oncogenic mutations

Tier changed: R24. Comments changed: Phase 2 NCI-COG Pediatric MATCH trial Arm C. NCT03213665. N=20. Tazemetostat showed limited activity (ORR 5%) in patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 33% of patients had prolonged stable disease (> 6 months), suggesting potential disease stabilization.Pediatric MATCH Treatment Trial.

Changed Tazemetostat in Solid tumours with SMARCB1 Oncogenic mutations

Tier changed: R24. Comments changed: Phase 2 NCI-COG Pediatric MATCH trial Arm C. NCT03213665. N=20. Tazemetostat showed limited objective response (ORR 5%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but achieved prolonged stable disease in 33% of patients, suggesting potential disease stabilization.Pediatric MATCH Treatment Trial. References changed: 10.1200/JCO.2022.40.16_suppl.10009NCT03213665.

Changed Vismodegib, Sonidegib in Basal cell carcinoma, Medulloblastoma with SMO D477G, E522K, G457S, S391N, D388N, N223D, L225R

Tier changed: R24. Comments changed: Preclinical study. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation, showing activity against tumors with acquired resistance to Smoothened antagonists, including SMO(D477G) mutant..

Thursday, 12 June 2025 (Version: 20250612AU)

New DB-1419 in Solid tumours with CD274 Protein expression: 4

Preclinical study. DB-1419, a bifunctional B7-H3xPD-L1 antibody-drug conjugate, demonstrated potent antitumor activity against multiple tumors with favorable pharmacokinetics and safety profiles, displaying efficient cellular internalization, direct cytotoxicity, antibody-dependent cellular cytotoxicity, and bystander effects. References: 40499141

New DB-1419 in Solid tumours with CD276 Protein expression: 4

Preclinical study. DB-1419, a bifunctional B7-H3xPD-L1 antibody-drug conjugate, demonstrated potent antitumor activity against multiple tumors with favorable pharmacokinetics and safety profiles, displaying efficient cellular internalization, direct cytotoxicity, antibody-dependent cellular cytotoxicity, and bystander effects. References: 40499141

New IBI3001 in Solid tumours with CD276 Protein expression: 4

Preclinical study. IBI3001, a B7-H3/EGFR bispecific ADC, demonstrated potent cytotoxicity in cancer cells with varying B7-H3 and EGFR expression across multiple solid tumors, and showed robust tumor growth inhibition in xenograft models. Note cytotoxicties were demonstrated across all expression levels. References: 10.1158/1538-7445.AM2024-LB055

New IBI3001 in Solid tumours with EGFR Protein expression: 4

Preclinical study. IBI3001, a B7-H3/EGFR bispecific ADC, demonstrated potent cytotoxicity in cancer cells with varying B7-H3 and EGFR expression across multiple solid tumors, and showed robust tumor growth inhibition in xenograft models. Note cytotoxicties were demonstrated across all expression levels. References: 10.1158/1538-7445.AM2024-LB055

New IBI334 in Solid tumours with EGFR Protein expression: 4

Preclinical study. IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, showed enhanced EGFR signal inhibition and potent efficacy in various xenograft models, with a large therapeutic window of >200 folds, indicating potential for safe and effective treatment of EGFR-driven solid tumors. References: 10.1158/1538-7445.AM2024-LB056

New VVD-442 in Solid tumours with ERBB2 Overexpression: 4

Preclinical study. Covalent binding to C242 in the PI3K p110 alpha RBD inhibits RAS-PI3K interaction, suppressing growth of RAS mutant and HER2 over-expressing tumors without inducing hyperglycemia. References: 10.1101/2024.12.17.629001

New BI-2493, BI-2865 in Solid tumours with HRAS Oncogenic mutations, Q95H: 4

Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666

New VVD-442 in Solid tumours with KRAS G12C: 4

Preclinical study. Covalent binding to C242 in the PI3K p110 alpha RBD inhibits RAS-PI3K interaction, suppressing growth of RAS mutant and HER2 over-expressing tumors without inducing hyperglycemia. References: 10.1101/2024.12.17.629001

New ACBI3 in Solid tumours with KRAS G12S, G12A, G12C, G12V, G13C, G13D, G13V, Q61E, Q61H, Q61P, A146P, A146T, A146V: 4

Preclinical study. A single small-molecule degrader, ACBI3, was designed to target 13 of the 17 most prevalent oncogenic KRAS mutants, achieving potent and selective degradation, and inducing tumor regression in KRAS mutant xenograft mouse models. References: 39298590

New BI-2493, BI-2865 in Solid tumours with KRAS Oncogenic mutations, G12A, G12C, G12D, G12F, G12V, G12S, G13C, G13D, V14I, L19F, Q22K, D33E, Q61H, K117N, A146V, A146T: 4

Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666

New BI-2493, BI-2865 in Solid tumours with NRAS Oncogenic mutations, L95H: 4

Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666

New ACBI3 in Solid tumours with KRAS G12R, Q61L, Q61R, Q61K: R2

Preclinical study. A single small-molecule degrader, ACBI3, was designed to target 13 of the 17 most prevalent oncogenic KRAS mutants, achieving potent and selective degradation, and inducing tumor regression in KRAS mutant xenograft mouse models. References: 39298590

New BI-2493, BI-2865 in Solid tumours with KRAS G12R, Q61L, Q61R, Q61K, A59T: R2

Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666

Changed Olaparib in Breast cancer with BRCA2 : 3

Alterations changed: Oncogenic mutations AND NOT Oncogenic mutations (germline).

Wednesday, 11 June 2025 (Version: 20250611AU)

New Olaparib in Breast cancer with BRCA1+ERBB2 BRCA1:Oncogenic mutation and NOT ERBB2:Overexpression and NOT ERBB2:Amplification: R2

Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer. References: 21862407

New Olaparib in Ovarian cancer with BRCA1 Oncogenic mutations: 3

Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer. References: 21862407

New Olaparib in Ovarian cancer with BRCA2 Oncogenic mutations: 3

Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer. References: 21862407

Changed Olaparib in Breast cancer with BRCA1 : 3

Alterations changed: Oncogenic mutations AND NOT Oncogenic mutations (germline).

Tuesday, 10 June 2025 (Version: 20250610AU)

New LY3214996 in Solid tumours with BRAF Oncogenic mutations: 4

Phase 1. NCT02857270. LY3214996, an ERK1/2 inhibitor, tumor PD inhibition in patients with advanced cancer, with tumor regression observed in 7 patients with BRAF/non-BRAF mutant cancers. References: 10.1200/JCO.2019.37.15_suppl.3001

New Ulixertinib in Solid tumours with BRAF Oncogenic mutations: 4

Phase 1 trial. NCT01781429. N=135. Ulixertinib, an ERK1/2 kinase inhibitor, showed an acceptable safety profile and early evidence of clinical activity in NRAS- and BRAF V600- and non-V600-mutant solid tumors with partial responses observed in 14% of evaluable patients. References: 29247021

New BDC-4182 in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 4

Preclinical study. BDC-4182, a CLDN18.2-targeting ISAC, demonstrated potent antigen-dependent activation of the immune system, significant tumor regression, and an acceptable safety profile in animal models. 10.1136/jitc-2024-SITC2024.1052. References: NCT06921837

New ADT-007 in Breast cancer with HRAS G12D: 4

Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells. References: 39700396

New BAY1436032 in Low-grade glioma with IDH1 R132: 4

Phase I trial. NCT02746081. BAY1436032 showed clinical activity in a subset of heavily pretreated subjects with lower grade glioma (LGG), with an objective response rate of 11% and stable disease in 43%, and a 3-month PFS rate of 0.31, while no objective responses were observed in glioblastoma, intrahepatic cholangiocarcinoma, or other tumor types. References: 33622704

New ADT-007 in Solid tumours, Pancreatic adenocarcinoma, Lung adenocarcinoma, Colon adenocarcinoma, Breast adenocarcinoma, Low-grade serous ovarian cancer, Melanoma, Gastric cancer with KRAS G12C, G12D, G12S, G12V, G13D, P121H, Amplification: 4

Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells. References: 39700396

New H231 in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 4

Preclinical study. ADCs targeting EGFR ligand epiregulin (EREG) demonstrate antitumor activity in colorectal cancer across RAS mutation status, offering a potential alternative to conventional EGFR-targeted therapy. References: 39693606

New ATX968 in Solid tumours with Microsatellite Instability High: 4

Preclinical study. Selective inhibition of DHX9 by a small-molecule inhibitor impairs proliferation of microsatellite instable-high and mismatch repair deficient cancers in vitro and xenograft models. References: 39589774

New ATX968 in Solid tumours with Mismatch repair Deficient: 4

Preclinical study. Selective inhibition of DHX9 by a small-molecule inhibitor impairs proliferation of microsatellite instable-high and mismatch repair deficient cancers in vitro and xenograft models. References: 39589774

New ADT-007 in Breast cancer, Melanoma with NRAS Q61K: 4

Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells. References: 39700396

New Xaluritamig in Prostate cancer with STEAP1 Protein expression: 4

Phase 1 study. Xaluritamig, a STEAP1-targeted T-cell engager, showed responses (49% PSA50; 24% ORR) in patients with metastatic castration-resistant prostate cancer, with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Note relationship between STEAP1 expression and response was not prospectively assessed in this study. References: 37861461

New Olaparib in Breast cancer with BRCA1 Promoter methylation: R2

Phase 2 COMETA-Breast study. NCT03205761. Olaparib showed limited antitumor activity in pretreated advanced triple-negative breast cancer patients with BRCA1/2 promoter methylation, with an ORR of 9% and median PFS of 2 months. References: 10.1200/JCO.2023.41.16_suppl.1093

New Olaparib in Breast cancer with BRCA2 Promoter methylation: R2

Phase 2 COMETA-Breast study. NCT03205761. Olaparib showed limited antitumor activity in pretreated advanced triple-negative breast cancer patients with BRCA1/2 promoter methylation, with an ORR of 9% and median PFS of 2 months. References: 10.1200/JCO.2023.41.16_suppl.1093

New BAY1436032 in Acute myeloid leukaemia with IDH1 R132: R2

Phase 1 study. NCT03127735. N=27. BAY1436032, an IDH1 inhibitor, showed modest clinical activity in IDH1-mutant AML with an overall response rate of 15% (4/27; 1 CRp, 1 PR, 2 MLFS) and median treatment duration of 6 months among responders. References: 32733012

New BAY1436032 in Glioblastoma, Intrahepatic cholangiocarcinoma, Solid tumours except Low-grade glioma with IDH1 R132: R2

Phase I trial. NCT02746081. BAY1436032 showed clinical activity in a subset of heavily pretreated subjects with lower grade glioma (LGG), with an ORR of 11% and SD in 43%, and a 3-month PFS rate of 0.31, while no objective responses were observed in glioblastoma, intrahepatic cholangiocarcinoma, or other tumor types. References: 33622704

New Crizotinib in Non-small cell lung cancer with MET Y1230C (Y1248C): R2

Case report. MET Y1230C mutation (0.3% pre-treatment frequency) emerged as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping, co-occurring with METex14 alteration D1010H, and was detected in ctDNA at progression after 13 months of treatment. References: 27666659

New MRK003 in Triple-negative breast cancer with NOTCH2 Rearrangements: R2

Preclinical study. NOTCH1 mutations and high N1-ICD levels correlated with GSI sensitivity in TNBC and ACC, while NOTCH2 rearrangements were associated with GSI resistance in TNBC cell lines. References: 25104330

Removed RAF dimer inhibitor in Solid tumours with BRAF alterations L597, L597Q, K601, K601E: Tier 4

Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with MLH1 alterations Promoter methylation: Tier 4

Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with MSH2 alterations Promoter methylation: Tier 4

Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with MSH6 alterations Promoter methylation: Tier 4

Removed AG-270 in Solid tumours with MTAP alterations Deletion: Tier 4

Removed Trametinib in Non-small cell lung cancer with NF1 alterations Oncogenic mutations: Tier 4

Removed Ulixertinib; LY3214996; LTT462; Ravoxertinib in Solid tumours with NF1 alterations Oncogenic mutations: Tier 4

Removed NRR2Mab in Urothelial carcinoma with NOTCH2 alterations Gain-of-function mutations: Tier 4

Removed MRK003 + paclitaxel in Solid tumours with NOTCH2 alterations Rearrangements: Tier 4

Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with PMS2 alterations Promoter methylation: Tier 4

Changed Venetoclax + Rituximab in Chronic lymphocytic leukaemia with BCL2 Overexpression: 1

Comments changed: TGA approved. Phase 3 trial. NCT02005471. N=389. Venetoclax-rituximab demonstrates significantly improved 2-year progression-free survival (85% vs 36%) compared to bendamustine-rituximab in relapsed or refractory chronic lymphocytic leukemia, with BCL2 overexpression being a characteristic of CLL cells..

Changed Blinatumomab in Acute lymphoblastic leukaemia with CD19 Protein expression: 1

Comments changed: Phase 3 trial. TOWER. NCT02013167. N=405. Blinatumomab significantly improved overall survival (7.7 vs 4.0 months), remission rates (44% vs 25%), and event-free survival (31% vs 12%) in adults with relapsed or refractory B-cell precursor ALL, including both Ph-positive and Ph-negative subtypes. Note that surface antigen CD-19 is lineage-specific to B-cells and constitutively expressed on the majority of B-cell precursor ALL blasts and does not represent a biomarker selection criteria..

Changed Therapy in Breast cancer with ERBB2 Amplification, Overexpression: 1

Therapy changed: Ado-Trastuzumab Emtansine.

Changed Therapy in Diffuse large B-cell lymphoma with CD79B Protein expression: 1B

Therapy changed: Polatuzumab vedotin + Bendamustine + RituximabPolatuzumab vedotin-piiq + Bendamustine + Rituximab.

Changed Trastuzumab deruxtecan in Non-small cell lung cancer, Endometrial cancer, Salivary gland cancer with ERBB2 Amplification: 3

Comments changed: Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%)..

Changed Therapy in Salivary gland cancers with ERBB2 Amplification: 3

Therapy changed: Ado-Trastuzumab Emtansine.

Changed Therapy in Breast cancer with ERBB2 Amplification, Overexpression: 3

Therapy changed: Tucatinib + Trastuzumab EmtansineTucatinib + Ado-Trastuzumab Emtansine.

Changed Therapy in Non-small cell lung cancer with ERBB2 Oncogenic mutations, V659E, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G778insCPG, G776delinsVC, exon 20 insertion: 3

Therapy changed: Ado-Trastuzumab Emtansine.

Changed Therapy in Gastroesophageal junction adenocarcinoma, Gastric Cancer with ERBB2 Overexpression: 3

Therapy changed: Ado-Trastuzumab Emtansine.

Changed Neratinib + Trastuzumab emtansine in Breast cancer with ERBB2 Overexpression, Amplification: 3

Comments changed: Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + Trastuzumab Emtansine achieved 33.3%-35.3% CNS ORR in HER2+ breast cancer brain metastases, with median OS of 20.9-30.2 months across three cohorts.Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + ado-trastuzumab emtansine achieved 33.3%-35.3% CNS ORR in HER2+ breast cancer brain metastases, with median OS of 20.9-30.2 months across three cohorts..

Changed RMC-4550 in Solid tumours with BRAF Class III mutations, G466V, G596R: 4

Comments changed: SHP2 inhibition by RMC-4550 is active in cancer models with class 3 BRAF mutants, NF1 loss, or KRASG12 mutations, suppressing RAS/MAPK signaling and cell growth by disrupting SOS1-mediated RAS-GTP loading.Cell line study demonstrating BRAF class III mutations are sensitive to SHP2 inhibition..

Changed Therapy in Non-small cell lung cancer with EGFR+ERBB2 EGFR:Oncogenic mutations and ERBB2:amplification: 4

Therapy changed: Osimertinib + Trastuzumab EmtansineOsimertinib + Ado-Trastuzumab Emtansine.

Changed Trastuzumab deruxtecan in Biliary tract cancer, Ovarian cancer with ERBB2 Amplification: 4

Comments changed: Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%)..

Changed Therapy in Colorectal adenocarcinoma with ERBB2 ERBB2:amplification and KRAS:G12D: 4

Therapy changed: Ado-Trastuzumab Emtansine.

Changed Therapy in Breast cancer with ERBB2 L755S: 4

Therapy changed: Ado-Trastuzumab Emtansine, Poziotinib.

Changed Therapy in Gastric cancer with ERBB2 MDK-ERBB2 fusion, Fusions: 4

Therapy changed: Trastuzumab, Trastuzumab EmtansineTrastuzumab, Ado-Trastuzumab Emtansine.

Changed Therapy in Non-small cell lung cancer with ERBB2 V659E: 4

Therapy changed: Lapatinib, Afatinib, Trastuzumab EmtansineLapatinib, Afatinib, Ado-Trastuzumab Emtansine.

Changed Therapy in Colorectal adenocarcinoma with ERBB2+KRAS ERBB2:amplification and KRAS:G12D: 4

Therapy changed: Ado-Trastuzumab Emtansine.

Changed Crizotinib in Non-small cell lung cancer with MET

Alterations changed: D1028H (D1010H)Y1230C (Y1248C). Tier changed: 4R2. Comments changed: Case report. MET Y1230C mutation (0.3% pre-treatment frequency) emerged as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping, co-occurring with METex14 alteration D1010H, and was detected in ctDNA at progression after 13 months of treatment.Case report. Pre-treatment D1010H sensitizing to crizotinib..

Changed AG-270 in Solid tumours with MTAP Deletion: 4

Comments changed: Phase 1 trial. NCT03435250. N=40. AG-270/S095033, a MAT2A inhibitor, achieved 2 partial responses and 5 patients with stable disease ≥16 weeks in patients with advanced MTAP-deleted malignancies. First curated: 2020-11-23.

Changed TetMYB in Solid tumours, Adenoid cystic carcinoma, Colorectal adenocarcinoma with MYB Alteration; Overexpression: 4

Comments changed: Phase1. MYPHISMO. NCT03287427. First-in-human trial evaluating the safety and efficacy of TetMYB vaccine in combination with anti-PD-1 antibody in patients with advanced solid cancers, including colorectal and adenoid cystic carcinoma..

Changed BET inhibitor in Solid tumours, Liquid cancers with MYC Amplification, Oncogenic mutations: 4

Comments changed: Review of bromodomain inhibitors, a new target class for drug development, highlighting the progress of BET inhibitors in clinical trials and discussing the potential of next-wave non-BET bromodomain inhibitors in oncology and non-oncology indications..

Changed BET inhibitor in Solid tumours, Liquid cancers with MYCN Amplification, Oncogenic mutations: 4

Comments changed: Preclinical studies demonstrated bromodomain inhibition as a therapeutic strategy in cancer, particularly for MYCN-amplified neuroblastoma, where BET bromodomain inhibitors downregulated the MYCN transcriptional program and impaired growth, inducing apoptosis, and conferred a significant survival advantage in in vivo models..

Changed eFT508 in Diffuse large B-cell lymphoma with MYD88 Gain-of-function mutations: 4

Comments changed: Preclinical study. MNK1/MNK2 inhibitor demonstrated anti-proliferative effects in DLBCL cell lines, reduced pro-inflammatory cytokine production, and showed anti-tumor activity in human lymphoma xenograft models.MNK inhibitor.

Changed MRK003 in Solid tumours with NOTCH1 Oncogenic mutations, Overexpression: 4

Comments changed: Preclinical study. NOTCH1 mutations and expression levels of HES4 are identified as biomarkers predictive of response to gamma-secretase inhibitor (GSI) in triple-negative breast cancer and adenoid cystic carcinoma.. References changed: 25104330, 24667249.

Changed MRK003 in Glioblastoma with NOTCH2 Gain-of-function mutations: 4

Comments changed: Pre-clinical study. NOTCH pathway blockade using gamma-secretase inhibitors depleted CD133-positive glioblastoma stem cells, inhibited neurosphere growth, and prolonged survival in xenograft models.Pre-clinical evidence.

Changed MRK003 in Non-small cell lung cancer with NOTCH3 Overexpression: 4

Comments changed: Preclinical study. Gamma-secretase inhibitor MRK-003 inhibited Notch3 signaling, reduced proliferation, and induced apoptosis in lung cancer cell lines in vitro and in vivo.Pre-clinical evidence.

Changed Exarafenib in Melanoma with NRAS Oncogenic mutations: 4

Comments changed: Phase 1/1b. NCT04913285. N=52. Exarafenib, a pan-RAF inhibitor, demonstrated preliminary clinical activity with 18% partial response and 47% stable disease in 34 patients across all dose levels with post-baseline tumor assessment..

Changed FOLFIRINOX in Pancreatic adenocarcinoma with RAD51C Oncogenic mutations (germline): 4

Comments changed: Case report. A patient with metastatic pancreatic adenocarcinoma and a germline RAD51C mutation showed a remarkable response to FOLFIRINOX, a platinum-containing chemotherapy regimen..

Changed Rucaparib, Niraparib in Ovarian cancer with RAD51C Promoter methylation: 4

Comments changed: Preclinical study. RAD51C promoter methylation loss causes PARP inhibitor resistance in high-grade serous ovarian carcinoma PDX models, where a single unmethylated copy of RAD51C is sufficient to drive resistance..

Changed RMC-4550 in Solid tumours with BRAF V600E, Class I mutations, Class II mutations, G469A: R2

Comments changed: SHP2 inhibition is active in cancers driven by class 3 BRAF mutants, NF1 loss, and certain KRASG12 mutants, which remain dependent on RAS nucleotide cycling, offering a potential therapeutic strategy for these currently intractable tumors.Cell line study..

Changed Palbociclib in Lung squamous cell carcinoma with CDK6 Amplification: R2

Comments changed: Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.Lung-MAP S1400C, ORR 6%.

Changed Palbociclib in Gastrointestinal stromal tumour with CDKN2A Deletion: R2

Comments changed: Phase 2. NCT01907607. In patients with advanced GIST refractory to imatinib and sunitinib with CDKN2A loss, palbociclib showed no significant clinical activity with 86% of patients having progressive disease at 4 months and ORR 0%.Phase 2. NCT01907607. ORR 0%..

Changed Palbociclib in Pancreatic adenocarcinoma, Biliary tract cancer with CDKN2A Deletion, Oncogenic mutations: R2

Comments changed: TAPUR study. N=22 (12 pancreatic, 10 biliary cancer). ORR 0%. Median PFS 7.2 and 7.3 weeks, and median OS 12.4 and 11.1 weeks in pancreatic and biliary cohorts respectively, with CDKN2A loss or mutation treated with palbociclib.TAPUR. N=22. ORR 0%..

Changed Trastuzumab deruxtecan in Colorectal adenocarcinoma, Bladder cancer with ERBB2 Amplification and NOT overexpression: R2

Comments changed: Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%)..

Changed Therapy in Colorectal adenocarcinoma with ERBB2 Amplification, Overexpression: R2

Therapy changed: Ado-Trastuzumab Emtansine + Pertuzumab.

Changed Therapy in Solid tumours except Breast cancer, Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification, Overexpression: R2

Therapy changed: Ado-Trastuzumab Emtansine.

Changed Trastuzumab in Breast cancer with ERBB2 L755S, D769Y, V842I, K753E: R2

Comments changed: Somatic HER2 mutations, such as L755S, V842I, K753I, and D769Y, are associated with resistance to certain anti-HER2 therapies, including trastuzumab and lapatinib, while others like S310F, S310Y, R678Q, D769H, or I767M show activities, and specific mutations like L755S or D769Y may have activity from neratinib or afatinib in HER2-positive breast cancer..

Changed Therapy in Breast cancer with ERBB2 L755S, L755P: R2

Therapy changed: Ado-Trastuzumab Emtansine, Lapatinib + Trastuzumab, Trastuzumab, Lapatinib + Capecitabine, Lapatinib + Letrozole, Lapatinib + Paclitaxel, Trastuzumab + Paclitaxel, Trastuzumab + Pertuzumab + Paclitaxel, Trastuzumab + Capecitabine.

Changed Lapatinib in Breast cancer with ERBB2 L755S, V842I, K753E: R2

Comments changed: Somatic HER2 mutations demonstrate varied therapeutic implications: L755S, V842I, K753I, and D769Y confer resistance to trastuzumab and lapatinib; S310F, S310Y, R678Q, D769H, and I767M are associated with favorable treatment outcomes; L755S and D769Y may respond to neratinib or afatinib..

Changed Lapatinib in Urothelial carcinoma with ERBB2 Overexpression: R2

Comments changed: Phase 3 trial. N=232. Maintenance lapatinib did not improve PFS (4.5 vs 5.1 months) or OS (12.6 vs 12.0 months) in HER1/HER2-positive metastatic urothelial bladder cancer patients after first-line chemotherapy, including in patients strongly positive for HER1/HER2..

Changed Therapy in Gastric cancer with ERBB2 ZNF207-ERBB2 fusion: R2

Therapy changed: Trastuzumab, Trastuzumab EmtansineTrastuzumab, Ado-Trastuzumab Emtansine.

Changed Pictilisib in Solid tumours with ERBB3 Q809R: R2

Comments changed: Preclinical study. Oncogenic ERBB3 mutations identified in colon and gastric cancers, with mutant ERBB3 oncogenic activity dependent on ERBB2, suggesting potential resistance to ERBB-targeting therapies unless ERBB2 is also inhibited..

Changed Cetuximab in Head and neck squamous cell carcinoma with ERBB4 Oncogenic mutations: R2

Comments changed: Preclinical study. Afatinib showed antitumor activity against ESCC and HNSCC cell lines with activating oncogenic EGFR and HER4 mutations, suggesting potential for targeted therapy in patients with such mutations, particularly in HNSCC where HER4 mutations are relatively frequent, indicating a possible resistance mechanism.No response in this cohort.

Changed GnRH agonist, Aromatase Inhibitor, Letrozole, Anastrozole, Exemestane, Tamoxifen in Breast cancer with ESR1 E380Q, V392I, S463P, V534E, P535H, L536R, L536Q, Y537S, Y537N, Y537C, D538G: R2

Comments changed: Review article discusses ESR1 mutations as a mechanism for acquired endocrine resistance in ER-positive breast cancer, occurring in approximately 20% of metastatic patients treated with endocrine therapies..

Changed Olaparib in Pancreatic adenocarcinoma with FANCD2 Oncogenic mutations, Oncogenic mutations (germline): R2

Comments changed: Two Phase 2 studies. N=46. Olaparib monotherapy showed limited antitumor activity in patients with pancreatic cancer with DDR-GAs, with a median PFS of 5.7 months and median OS of 13.6 months, suggesting a potential therapeutic opportunity for a subset of patients with PDAC harbouring DDR genetic alterations.Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold..

Changed Zoligratinib in Cholangiocarcinoma with FGFR2 L618F: R2

Comments changed: Preclinical and clinical study. FGFR2 extracellular domain in-frame deletions (EID) in intrahepatic cholangiocarcinoma are present in 2.8% of patients, conferring initial sensitivity to FGFR inhibitors. The L618F FGFR2 kinase domain mutation leads to acquired resistance, which can be overcome by futibatinib..

Changed Dovitinib in Cholangiocarcinoma with FGFR2 N549S, N549H: R2

Comments changed: Preclinical study. Comprehensive functional evaluation of 160 nonsynonymous FGFR mutations and ten fusion genes revealed varying transforming activity and sensitivity to seven FGFR TKIs, with several hotspot mutants showing relative resistance, and compound mutations affecting TKI-sensitivity..

Changed Infigratinib, AZD4547, Zoligratinib in Solid tumours with FGFR3 V443, V555M: R2

Comments changed: Phase 1/2 trial. BGJ398. N = 67. Patients with metastatic urothelial carcinoma bearing FGFR3 alterations. Overall response rate of 25.4% and disease control rate of 64.2% observed. Preclinical study identified gatekeeper mutation (FGFR3(V555M)) in FGFR3 as a mechanism of acquired resistance to FGFR inhibitors..

Changed Sotorasib in Solid tumours with KRAS V8L, G13D, V14L, K16T, A59S, Q61R, R68S, G77V, Y96D, Y96C, K117N, D119H, A146P: R2

Comments changed: Phase1/2 study. N=38. KRAS(G12C) mutant cancers treated with adagrasib or sotorasib. Putative mechanisms of resistance detected in 45% patients, including acquired KRAS alterations, bypass mechanisms, and histologic transformation to squamous-cell carcinoma. On-target resistance identified by deep mutational scanning and in vitro validated..

Changed Adagrasib in Solid tumours with KRAS V9F, G13D, V14L, K16T, A59S, Q61R, E62D, Y64N, R68S, M72L, G77V, H95D, H95Q, H95R, Y96D, Y96C, Q99K, K117N, D119H, A146P: R2

Comments changed: Phase 1/2 study. NCT03785249. N=38. Mechanisms of resistance to Adagrasib include acquired KRAS alterations (G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and KRAS(G12C) allele amplification) and bypass mechanisms involving MET amplification, NRAS, BRAF, MAP2K1, RET mutations, ALK, RET, BRAF, RAF1, FGFR3 fusions, and NF1, PTEN loss-of-function mutations. Histologic transformation to squamous-cell carcinoma was observed in 2 lung adenocarcinoma patients.On-target resistance identified by deep mutational scanning and in vitro validated..

Changed Pembrolizumab in Colorectal adenocarcinoma with KRAS+Microsatellite Instability KRAS:Oncogenic mutations AND Microsatellite Instability:High: R2

Comments changed: Phase 3 KEYNOTE-177 trial. NCT02563002. N=307. Pembrolizumab demonstrated superior progression-free survival (16.5 vs 8.2 months, HR 0.60) with reduced treatment-related adverse events (22% vs 66%) in MSI-H/dMMR metastatic colorectal cancer, with 83% of responders maintaining ongoing responses at 24 months. The KRAS subgroup did not show PFS benefit over chemotherapy.KRAS subgroup showed no PFS benefit over chemotherapy in KEYNOTE-177.

Changed Pembrolizumab in Colorectal adenocarcinoma with KRAS+Mismatch repair KRAS:Oncogenic mutations AND Mismatch repair:deficient: R2

Comments changed: Phase 3 KEYNOTE-177 trial. NCT02563002. N=307. Pembrolizumab demonstrated superior progression-free survival (16.5 vs 8.2 months, HR 0.60) with reduced treatment-related adverse events (22% vs 66%) in MSI-H/dMMR metastatic colorectal cancer, with 83% of responders maintaining ongoing responses at 24 months. The KRAS subgroup did not show PFS benefit over chemotherapy.KRAS subgroup showed no PFS benefit over chemotherapy in KEYNOTE-177.

Changed Duligotuzumab + FOLFIRI in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: R2

Comments changed: Phase 2. NCT01652482. In RAS wild-type metastatic colorectal cancer, duligotuzumab plus FOLFIRI showed no improvement in PFS or OS compared with cetuximab and FOLFIRI, with a trend for lower ORR and different toxicity profiles.NCT01652482. Phase 2. In RAS wild-type metastatic colorectal cancer, there was no improvement of duligotuzumab plus FOLFIRI compared with cetuximab and FOLFIRI..

Changed Cetuximab in Breast cancer, Non-small cell lung cancer, Ovarian cancer with KRAS+NRAS+BRAF NOT KRAS:Oncogenic mutation and NOT NRAS:Oncogenic mutation and NOT BRAF:Oncogenic mutation: R2

Comments changed: Phase 2 TAPUR study. NCT02693535. N=49. Cetuximab showed no objective responses in breast cancer (N=10) and NSCLC (N=10), and no objective responses but 4 patients with stable disease for at least 16 weeks in ovarian cancer (N=29).NCT02693535. TAPUR. N=49 including breast, NSCLC, and ovarian cancers. ORR 0%..

Changed Rucaparib in Non-small cell lung cancer with Loss-of-heterozygosity score High: R2

Comments changed: Phase 2 Lung-MAP Sub-Study, S1900A. NCT03845296. N=64 (27 squamous; 37 non-squamous). Rucaparib showed limited efficacy in NSCLC patients with high genomic LOH and/or BRCA1/2 mutations, with an ORR of 7% (4% squamous; 9% non-squamous) and median PFS of 3.2 months (non-squamous) and 2.9 months (squamous). Genomic LOH does not predict activity.Phase 2 Lung-MAP Sub-Study, S1900A. ORR 7%. Genomic LOH does not predict activity..

Changed Dabrafenib + Trametinib, Trametinib in Colorectal adenocarcinoma with MAP2K1 F53L: R2

Comments changed: Paired pre-post treatment sequencing identified MAPK pathway alterations, including KRAS amplification, BRAF amplification, and MEK1 mutation, driving clinical acquired resistance to RAF inhibitor combinations in BRAF-mutant colorectal cancer..

Changed Cabozantinib in Solid tumours with MDM2 Amplification: R2

Comments changed: Preclinical study. MDM2 amplification identified as a potential mechanism of primary or acquired resistance to cabozantinib in RET-rearranged lung cancers, with MDM2 inhibitors showing effectiveness in suppressing tumor growth.Anti-RET activity. References changed: 10.1200/JCO.2016.34.15_suppl.906832083997.

Changed Osimertinib in Non-small cell lung cancer with MET Amplification: R2

References changed: 27252416, 3793834827252416; 37938348.

Changed Crizotinib in Non-small cell lung cancer with MET L1195V (L1213V), Y1230 (Y1248), D1228N (D1246N), D1228 (D1246), D1246 (D1228), Y1248 (Y1230), G1163 (G1181): R2

Comments changed: Evidence for Crizotinib and potential sequential use of type II MET inhibitors (cabozantinib, glesatinib, merestinib) in NSCLC patients with MET exon 14 skipping mutations after developing resistance to type I MET inhibitors.Strong evidence for Crizotinib. Capmatinib inferred.

Changed Pembrolizumab in High-grade gliomas with Mismatch repair Deficient: R2

Comments changed: Single-agent pembrolizumab showed a DCR of 31% with no objective responses (ORR 0%) and four patients with stable disease in a prospective study of 13 recurrent high-grade gliomas with MMR protein loss.N=13. Single-agent PD-1 inhibitor showed no response in a prospective case series (ORR 0%) with 4 SD..

Changed Pembrolizumab in High-grade gliomas, Anaplastic astrocytoma, Glioblastoma with Mismatch repair Deficient: R2

Comments changed: Phase 2 trial. N=13. Median age 43 years. ORR 0%. DCR 31% (4 stable disease). TMB ranged 6.8-23.4 mutations/megabase. Pembrolizumab showed no apparent benefit in patients with recurrent HGG and MMR loss.N=13. ORR 0%. All patients were microsatellite stable..

Changed Durvalumab in Endometrial cancer with Mismatch repair Proficient, NOT Deficient: R2

Comments changed: Phase 2 trial. NCT03015129. Durvalumab showed promising activity in dMMR advanced endometrial carcinoma with ORR of 47% and median PFS of 8.3 months, but limited activity in pMMR advanced endometrial carcinoma with ORR of 3% and median PFS of 1.8 months.PHAEDRA. Phase 2. ORR in the pMMR cohort was 3% (1 of 35) with median PFS of 1.8 months..

Changed Pembrolizumab + Carboplatin + Pemetrexed in Non-small cell lung cancer with NRG1 Fusions: R2

Comments changed: Retrospective registry-based study. NRG1 fusion-positive lung cancers showed heterogeneity in molecular, pathological, and clinical characteristics, with low ORR to platinum-doublet chemotherapy (13%), taxane-based chemotherapy (14%), chemoimmunotherapy (0%), and single-agent immunotherapy (20%), while afatinib achieved an ORR of 25%.Retrospective registry-based study. Chemoimmunotherapy ORR 0%..

Changed Androgen receptor antagonist, GnRH agonist, CYP17A1 inhibitor, Enzalutamide, Apalutamide in Prostate cancer with RB1 Oncogenic mutations: R2

Comments changed: Review. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer were discussed, including restored AR signalling, AR bypass signalling, and complete AR independence, presenting new challenges for long-term disease control..

Changed Androgen receptor antagonist, GnRH agonist, CYP17A1 inhibitor, Enzalutamide, Apalutamide in Prostate cancer with TP53 Oncogenic mutations: R2

Comments changed: Preclinical study. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer were reviewed, including restored AR signalling, AR bypass signalling, and complete AR independence, presenting new challenges for long-term disease control.Off-target mechanism.

Monday, 9 June 2025 (Version: 20250609AU)

New Selumetinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 1

Phase 3 KOMET trial. NCT04924608. N=145. Selumetinib significantly improved ORR (19.7% vs 5.4%) compared to placebo in adults with NF1 and symptomatic, inoperable plexiform neurofibroma. References: 10.1200/JCO.2025.43.16_suppl.3014

New Trastuzumab deruxtecan in Non-small cell lung cancer, Endometrial cancer, Salivary gland cancer with ERBB2 Amplification: 3

Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%). References: 10.1200/JCO.2025.43.16_suppl.3020

New JSKN003 in Gastroesophageal junction adenocarcinoma, Gastric Cancer, Colorectal adenocarcinoma with ERBB2 Overexpression: 3

Pooled analysis of JSKN003-101 and JSKN003-102 trials. NCT05494918, NCT05744427. N=40. JSKN003 showed activity in heavily pretreated patients with advanced HER2-overexpressing gastrointestinal tumors, with ORR of 67% and median PFS of 9.6 months. References: 10.1200/JCO.2025.43.16_suppl.3022

New GFH375 in Solid tumours, Non-small cell lung cancer, Pancreatic adenocarcinoma with KRAS G12D: 3

Phase 1/2 trial. NCT06500676. N=32. Single-agent GFH375, a KRAS G12D inhibitor that targets both GTP-bound and GDP-bound states of mutant KRASG12D protein, showed anti-tumor activity in patients with advanced solid tumors, with ORR of 27% and DCR of 86% across dose range. ORR 42% in 12 PDAC and 52% in PDAC at target dose range. References: 10.1200/JCO.2025.43.16_suppl.3013

New BC3195 in Non-small cell lung cancer with EGFR Oncogenic mutations: 4

Phase 1. NCT05957471, N=56, BC3195, an ADC targeting CDH3, showed preliminary activity in heavily pretreated patients with NSCLC, particularly in EGFR-mutant NSCLC with an ORR of 50% and mPFS > 6 months. References: 10.1200/JCO.2025.43.16_suppl.3019

New Trastuzumab deruxtecan in Biliary tract cancer, Ovarian cancer with ERBB2 Amplification: 4

Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%). References: 10.1200/JCO.2025.43.16_suppl.3020

New LY4170156 in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with FOLR1 Protein expression: 4

Phase 1a/b study. NCT06400472. LY4170156, an ADC targeting folate receptor alpha, showed a preliminary ORR of 38% (5/13) in HGSOC patients with varying FRα expression levels and prior mirvetuximab soravtansin treatment. References: 10.1200/JCO.2025.43.16_suppl.3023

New ADRX-0706 in Solid tumours with NECTIN4 Protein expression: 4

Phase 1 trial. NCT06036121. N=53. ADRX-0706, a Nectin-4 targeting antibody-drug conjugate (ADC), showed anti-tumor activity in 30 response-evaluable subjects treated at doses ≥8 mg/kg, with a confirmed complete response in a cervical cancer patient. The study reported an ORR of 17%, including 5 objective responses, and a DCR of 47%, with 9 patients experiencing stable disease. Nectin-4 expression is retrospective analysis criteria and not prospectively assessed. References: 10.1200/JCO.2025.43.16_suppl.3018

New BRY812 in Solid tumours with SLC39A6 Protein expression: 4

Phase 1 trial. NCT06038058. N=36. BRY812, an ADC targeting LIV-1, demonstrated an ORR of 24% (8/34) in breast cancer, with response rates increasing to 43% (6/14) in patients with high LIV-1 expression (PS2+). References: 10.1200/JCO.2025.43.16_suppl.3021

New BAT8008 in Solid tumours with TACSTD2 Protein expression: 4

Phase 1 study. NCT05620017. N=170. BAT8008 showed activity in advanced cervical cancer (ORR 36%, PFS 6.8 months) and oesophageal cancer (ORR 23%, PFS 5.3 months). References: 10.1200/JCO.2025.43.16_suppl.3024

New Trastuzumab deruxtecan in Colorectal adenocarcinoma, Bladder cancer with ERBB2 Amplification and NOT overexpression: R2

Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%). References: 10.1200/JCO.2025.43.16_suppl.3020

New Tazemetostat in Epithelioid sarcoma, Atypical teratoid rhabdoid tumor with EZH2 Y666N: R2

Preclinical study. Identified molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors, and developed a combination strategy using AURKB targeting to circumvent resistance. References: 38315003

New Tazemetostat in Epithelioid sarcoma, Atypical teratoid rhabdoid tumor with RB1 Deletion, Oncogenic mutations: R2

Preclinical study. Identified molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors, and developed a combination strategy using AURKB targeting to circumvent resistance. References: 38315003

Changed Mirvetuximab soravtansine in Ovarian cancer with FOLR1 : 2

Alterations changed: Protein expression.

Changed Repotrectinib with ROS1 Fusion: 3

Cancer type(s) changed: Solid tumours

Changed AZD9833, Elacestrant, Tamoxifen in Breast cancer with ESR1 : 4

Alterations changed: F404L, D538G and F404L, E380Q and F404L. Comments changed: Novel ESR1 F404 mutations (F404L, F404I, and F404V) were acquired in 4% of patients in the plasmaMATCH Cohort A trial (NCT03182634, N=69). These mutations confer resistance to fulvestrant when combined with preexisting activating ESR1 mutations. In cell line models, F404L demonstrates sensitivity to tamoxifen and select SERDs. These mutations may be potentially targetable by oral ERalpha degraders in clinical development.plasmaMATCH. Treatment emergent mutation causing acquired resistance at the ligand binding domain. In cell line model, F404L is sensitive to tamoxifen and select SERDs..

Changed Fulvestrant in Breast cancer with ESR1 : R2

Alterations changed: F404L, F404I, F404V, D538G and F404L, E380Q and F404L. Comments changed: Novel ESR1 F404 mutations (F404L, F404I, and F404V) were acquired in 4% of patients in the plasmaMATCH Cohort A trial (NCT03182634, N=69). These mutations confer resistance to fulvestrant when combined with preexisting activating ESR1 mutations. In cell line models, F404L demonstrates sensitivity to tamoxifen and select SERDs. These mutations may be potentially targetable by oral ERalpha degraders in clinical development.plasmaMATCH. Treatment emergent mutation causing acquired resistance at the ligand binding domain.. References changed: 37982575, 10.1200/JCO.2022.40.16_suppl.1009.

Sunday, 8 June 2025 (Version: 20250608AU)

Friday, 6 June 2025 (Version: 20250606AU)

New ABBV-706 in High-grade well-differentiated neuroendocrine tumour, Neuroendocrine carcinoma, Solid tumour with SEZ6 Protein expression: 3

Phase 1. NCT05599984. ABBV-706, a SEZ6-targeting antibody-drug conjugate, showed preliminary efficacy in high-grade neuroendocrine neoplasms (NENs) with an overall objective response rate of 31% (20/64) and median progression-free survival of 6.8 months. References: 10.1200/JCO.2025.43.16_suppl.105

New SHR-1826 in Solid tumours with MET Overexpression, Amplification, Oncogenic mutation: 3

Phase 1 study. NCT06094556. N=116. SHR-1826, a c-MET-directed antibody-drug-conjugate, demonstrated a manageable safety profile and promising anti-cancer activity in heavily pretreated advanced solid tumors, particularly in NSCLC patients with an ORR of 40% and median PFS of 6.8 months. References: 10.1200/JCO.2025.43.16_suppl.106

New Sevabertinib in Non-small cell lung cancer with EGFR Exon 20 insertions, C797S: 4

Phase 1. NCT05099172. BAY2927088 is an oral TKI targeting EGFR and HER2 mutations that demonstrates strong potency and high selectivity for mutant versus wild-type EGFR, showing activities in NSCLC patients with EGFR exon 20 insertion mutations and EGFR C797S acquired resistance mutation. References: 10.1158/1538-7445.AM2023-CT126

New Sevabertinib in Non-small cell lung cancer with ERBB2 Exon 20 insertion mutation, A775_G776insYVMA (Y772_A775dup), G776delinsVC, S310F, S335C, L755S: 4

Preclinical study. BAY 2927088 showed strong antiproliferative activity against various HER2 mutations, including exon 20 insertion mutations (A775insYVMA, G776delinsVC) and point mutations (S310F, S335C, L755S), in isogenic Ba/F3 cell lines and patient-derived xenograft models. References: 10.1158/1538-7445.AM2023-4035

New DM002 in Solid tumours with MUC1 Protein expression: 4

Preclinical study. DM002 is a bispecific antibody-drug conjugate targeting HER3 and the juxtamembrane domain of MUC1, demonstrating endocytic and anti-tumor activity in patient-derived xenograft models of lung, breast, gastric, and pancreatic cancers. References: 10.1158/1538-7445.AM2023-LB214

Changed Izalontamab brengitecan in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: Oncogenic mutations.

Changed Sevabertinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: Exon 20 insertion, Oncogenic mutations.

Changed NVL-655 in Solid tumours, Non-small cell lung cancer with ALK : 4

Alterations changed: G1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletionG1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion.

Wednesday, 4 June 2025 (Version: 20250604AU)

Changed GSK126 in Ovarian clear cell carcinoma with ARID1A Oncogenic mutations: 4

Comments changed: Preclinical study. EZH2 inhibition showed synthetic lethality in ARID1A-mutated ovarian cancer cells, with regression of ARID1A-mutated ovarian tumors in vivo..

Changed Molibresib, JQ1 in Ovarian clear cell carcinoma with ARID1A Oncogenic mutations: 4

Comments changed: Preclinical study. ARID1A mutation sensitises ovarian clear cell carcinomas to BET inhibitors, causing lethal interaction and inhibiting proliferation in cell lines, xenografts, and patient-derived xenograft models..

Changed M6620 in Solid tumours with ARID1A Oncogenic mutations: 4

Comments changed: Phase 1 trial of ATR inhibitor M6620, achieving 1 CR in a patient with ATM loss and ARID1A mutation, and 1 PR in a platinum-refractory and PARP inhibitor-resistant BRCA1 ovarian cancer patient when combined with carboplatin.1 CR from NCT02157792, with ATM loss.

Changed M6620 in Solid tumours with ARID1A Oncogenic mutations: 4

Comments changed: Preclinical study. ARID1A deficiency sensitises tumour cells to ATR inhibitors, triggering premature mitotic entry, genomic instability, and apoptosis, representing a novel synthetic lethal therapy for ARID1A mutant tumours.Cell line study.

Changed Olaparib, Veliparib, Rucaparib in Solid tumours with ARID1A Oncogenic mutations: 4

Comments changed: Preclinical study. ARID1A deficiency impairs DNA damage checkpoint, sensitising cells to PARP inhibitors, providing a potential therapeutic strategy for patients with ARID1A-mutant tumors.Pre-clinical only.

Changed Nivolumab, Atezolizumab in Urothelial carcinoma with ARID1A Oncogenic mutations: 4

Comments changed: Retrospective biomarker study. ARID1A mutation and CXCL13 expression individually correlated with improved OS in mUCC patients receiving ICT, with combinatorial biomarker analysis suggesting further improved OS prediction..

Changed Olaparib, Rucaparib, Talazoparib in Solid tumours with ARID2 Loss-of-function mutations, Loss of protein expression: 4

Comments changed: Preclinical study. PBRM1 deficiency, occurring in 40% of clear cell renal cell carcinomas, confers synthetic lethality to DNA repair inhibitors, with PARP and ATR inhibitors showing promise in PBRM1-defective cancer models..

Changed Olaparib in Colorectal adenocarcinoma with ATM Loss-of-function mutations: 4

Comments changed: Preclinical study. ATM-deficient colorectal cancer cells are sensitive to PARP inhibitor olaparib, with enhanced sensitivity observed upon p53 depletion or ATM inhibition..

Changed Olaparib in Gallbladder cancer with ATM : 4

Alterations changed: Loss-of-function mutations, S1905Ifs*25. Comments changed: Case report. A patient with gallbladder carcinoma harboring an ATM-inactivating mutation (ATM S1905Ifs*25) responded to olaparib with a progression-free survival of 13 months..

Changed Olaparib in Prostate cancer with ATM Loss-of-function mutations: 4

Comments changed: Case reports..

Changed Adavosertib in Solid tumours with ATRX Loss-of-function mutations: 4

Comments changed: Preclinical study. ATRX-mutant cancers identified as selectively vulnerable to WEE1 inhibition through a genome-wide CRISPR-Cas9 screen, with AZD1775 showing robust inhibition of ATRX-deficient cell lines and xenografts..

Changed EPZ011989 in Mesothelioma with BAP1 Oncogenic mutations: 4

Comments changed: Preclinical study. Loss of BAP1 function leads to increased EZH2 expression, and BAP1-mutant cells are sensitive to EZH2 inhibition.Cell line study only.

Changed Talazoparib in Prostate cancer with BRCA1 Oncogenic mutations: 4

Comments changed: TALAPRO-1. Phase 2. In BRCA1 mutants N=4. PR 2/4.TALAPRO-1. Phase 2. N=4. PR 2/4.

Changed Neratinib, Fulvestrant + Neratinib in Breast cancer with ERBB2 T798I, L785F, D769Y: R2

Comments changed: Preclinical and clinical study. HER2 mutations define a targetable breast cancer subset. Concurrent activating HER2 or HER3 alterations and acquisition of multiple HER2-activating events, as well as gatekeeper alterations, were associated with de novo and acquired resistance to neratinib.Gatekeeper mutation.

Changed Trastuzumab, Ado-Trastuzumab Emtansine in Gastric cancer with ERBB2 ZNF207-ERBB2 fusion: R2

Comments changed: Preclinical study. HER2 fusions (ZNF207-HER2 and MDK-HER2) were identified as oncogenic drivers in gastric cancer, with ZNF207-HER2 fusion not responsive to trastuzumab due to impaired binding..

Changed AZD4547 in Solid tumours with FGFR1 Amplification: R2

Comments changed: Phase 2 NCI-MATCH trial. AZD4547 showed limited activity in tumors with FGFR aberrations, with confirmed partial responses in 8% of patients, primarily in those with FGFR1-3 point mutations or fusions.No response in these cohorts.

Changed Ponatinib, Dovitinib, Infigratinib in Solid tumours with FGFR1 N564K: R2

Comments changed: Preclinical study. Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1 (FGFR1) showed that N546K and V561M mutants had varying affinities for different ATP-competitive inhibitors, with V561M mutant showing reduced affinity for PD173074 and N546K showing increased affinity for AMP-PNP.Molecular hinge.

Changed Infigratinib, AZD4547, Zoligratinib in Solid tumours with FGFR1 V561M: R2

Comments changed: Preclinical study. Resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas is associated with either an activating V561M Gatekeeper mutation in the FGFR1 kinase domain or PTEN inactivation. Combined inhibition of FGFR and PI3K pathways shows additive effect in overcoming resistance..

Changed Fulvestrant + Ribociclib in Breast cancer with FGFR2 Amplification: R2

Comments changed: Preclinical study. FGFR1 amplification/alteration identified as a resistance mechanism to CDK4/6 inhibitors in ER+ breast cancer, with FGFR tyrosine kinase inhibitors (TKIs) abrogating this resistance and potentially improving treatment outcomes..

Changed AZD4547 in Solid tumours with FGFR2 Amplification: R2

Comments changed: Phase 2 NCI-MATCH trial. AZD4547 showed limited activity in tumors with FGFR aberrations, with confirmed partial responses in 8% of patients, primarily in those with FGFR1-3 point mutations or fusions.No response in these cohorts.

Changed Infigratinib in Cholangiocarcinoma with FGFR2 E565A, L617M: R2

Comments changed: Preclinical study. FGFR2 kinase domain E565A and L617M are potential drivers of acquired resistance to infigratinib in FGFR2-fusion cholangiocarcinoma..

Changed Osimertinib, Gefitinib in Non-small cell lung cancer with FGFR2 Fusions, FGFR2-CCDC6 fusion, FGFR2-KIAA1598 fusion, FGFR2-TACC2 fusion: R2

Comments changed: FGFR2/3 fusions were identified as an acquired resistance mechanism in lung adenocarcinoma following EGFR TKI treatment. Combination of EGFR TKIs and FGFR TKIs showing clinical benefit..

Changed Trametinib in Melanoma with NF1 Oncogenic mutations, Loss-of-function mutations

Tier changed: 4R2. Comments changed: Case report. A patient with NF1-mutated melanoma refractory to immunotherapy and chemotherapy responded to trametinib, a MEK inhibitor, with a DOR of 5 months, and showed increased CD8+ infiltration and PD-L1 expression during treatment.Case report. Duration of response 5 months..

Changed Binimetinib in Solid tumours except melanoma with NRAS G12, G13, Q61: R2

Comments changed: Phase 2 NCI-MATCH trial. NRAS subprotocol. Single-agent binimetinib showed limited efficacy with an ORR of 2%. Notably, a patient with malignant ameloblastoma harboring a codon 61 NRAS mutation achieved a durable partial response, and patients with colorectal cancer bearing a NRAS codon 61 mutation had significantly longer OS and PFS compared to those with codon 12 or 13 mutations.NCI-MATCH. NRAS subprotocol. ORR 2% with a single responder..

Changed Ivosidenib in Acute myeloid leukaemia with NRAS Oncogenic mutations: R2

Comments changed: Phase 1 trial. NCT02074839. N=174. Multiple mechanisms of resistance to ivosidenib have been identified in IDH1-mutant relapsed/refractory AML. Primary resistance is associated with RTK pathway mutations, while acquired resistance involves second-site IDH1/IDH2 mutations that restore 2-HG production. NRAS mutations are associated with reduced response rates compared to wild-type NRAS.NRAS- reduced response rate compared with WT NRAS.

Changed Larotrectinib in Solid tumours with NTRK1 Alterations AND NOT fusion: R2

Comments changed: Pooled analysis of larotrectinib trials. For non-fusion NTRK1/2/3 alterations, only one response was seen (of 73) with short duration of response.One PR (of 73) with short DOR..

Changed Larotrectinib in Solid tumours with NTRK2 Alterations AND NOT fusion: R2

Comments changed: Pooled analysis of larotrectinib trials. For non-fusion NTRK1/2/3 alterations, only one response was seen (of 73) with short duration of response.One PR (of 73) with short DOR..

Changed Larotrectinib in Solid tumours with NTRK3 Alterations AND NOT fusion: R2

Comments changed: Pooled analysis of larotrectinib trials. For non-fusion NTRK1/2/3 alterations, only one response was seen (of 73) with short duration of response.One PR (of 73) with short DOR..

Changed LY3023414 in Endometrial cancer with PTEN Loss-of-function mutations: R2

Comments changed: "Phase 2 study. N=28 with 25 evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months. LY3023414, a dual PI3K/mTOR inhibitor, showed modest activity in heavily pretreated advanced endometrial cancer with PI3K pathway mutations, but no correlation between molecular alterations and response was observed..

Tuesday, 3 June 2025 (Version: 20250603AU)

New Entrectinib in Non-small cell lung cancer with ALK F1245V: 3

Phase 1/2 ALKA-372-001 and STARTRK-1 trials. ALK F1245V mutant neuroblastoma achieved durable confirmed partial response lasting 8.3 months. References: 28183697, 10.1200/jco.2015.33.15_suppl.2517

New Uprosertib in Solid tumours with AKT2 Oncogenic mutations: 4

"Preclinical study. Selectivity profiling of Akt inhibitors GSK690693 and GSK2141795. References: 23795919

New Alectinib in Inflammatory myofibroblastic tumour with ALK Fusions: 4

Case report. A patient with inflammatory myofibroblastic tumor (IMT) harboring a novel SQSTM1-ALK fusion gene demonstrated a marked and durable response to alectinib, sustaining for 17 months without significant adverse events. References: 30790150

New Ceritinib in Inflammatory myofibroblastic tumour with ALK Fusions: 4

Case report. A patient with unresectable ALK-negative inflammatory myofibroblastic tumor (IMT) carrying a TFG-ROS1 fusion experienced partial response to ceritinib, a ROS1 inhibitor. References: 31805529

New BGB-53038 in Solid tumours with KRAS Amplification: 4

For trial matching only. Do not include unless more evidence. References: NCT06585488

Removed Capmatinib in Non-small cell lung cancer with MET alterations Amplification: Tier 3

Changed Crizotinib in Anaplastic large cell lymphoma with ALK Fusions, EML4-ALK Fusion: 2

Comments changed: Not TGA approved. FDA approved. Phase 1b PROFILE 1013 study. NCT01121588. N=44. demonstrated crizotinib's durable activity in ALK-positive lymphomas (ORR 53%, 8 CRs, 1 PR, 2-year PFS 63%) and inflammatory myofibroblastic tumors (ORR 67%, 1 CR, 5 PRs, 2-year PFS 67%).Not TGA approved; FDA approved..

Changed Lenalidomide + Rituximab in Follicular lymphoma, Marginal zone lymphoma with CD20 Protein expression: 2

Comments changed: Phase 2 trial. N=45. Previously untreated MZL patients treated with lenalidomide and rituximab showed ORR of 93% with 70% CR/CRu. Median PFS was 59.8 months and 5-year OS was 96% at median follow-up of 75.1 months..

Changed Ensartinib in Non-small cell lung cancer with ALK C1156Y, C1156T, L1196M: 3

Comments changed: Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors..

Changed Entrectinib in Non-small cell lung cancer with ALK C1156Y, C1156T, L1196M: 3

Comments changed: Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors..

Changed Entrectinib in Non-small cell lung cancer with ALK : 3

Alterations changed: EML4-ALK Fusion, Fusions, VCL-ALK fusion, CAD-ALK fusion, F1245V. Comments changed: Phase 1/2 ALKA-372-001 and STARTRK-1 trials. Entrectinib demonstrated antitumor activity in TKI-naive patients with ALK fusions, achieving an ORR of 57% (4/7) with a median duration of response of 7.4 months.. References changed: 28183697, 10.1200/jco.2015.33.15_suppl.2517.

Changed Brigatinib in Non-small cell lung cancer with ALK I1151ins, L1152P, L1152R, C1156Y, C1156T, F1174C, F1174L, F1174V, L1196M, S1206C, S1206Y, G1269A, G1269S: 3

Comments changed: Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors..

Changed Lorlatinib in Non-small cell lung cancer with ALK I1151ins, L1152P, L1152R, C1156Y, C1156T, I1171T, I1171N, I1171S, F1174C, F1174L, F1174V, L1196M, G1202R, S1206C, S1206Y, E1210K, G1269A, G1269S: 3

Comments changed: Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors..

Changed Ceritinib in Non-small cell lung cancer with ALK I1171T, I1171N, L1196M, S1206C, S1206Y, G1269A, G1269S: 3

Comments changed: Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors..

Changed Alectinib in Non-small cell lung cancer with ALK L1152P, L1152R, C1156Y, C1156T, F1174C, F1174L, F1174V, L1196M, S1206C, S1206Y, G1269A, G1269S: 3

Comments changed: Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors..

Changed Trametinib in Melanoma with BRAF G469R, A598_T599insV, AGAP3-BRAF fusion, L597Q, T470R: 3

Comments changed: Phase 2. NCT02296112. Trametinib in non-V600 BRAF mutation and BRAF fusions. ORR was 33% (3/9). Median PFS 7.3 months.Phase 2. NCT02296112. Trametinib in non-V600 BRAF fusions. ORR was 33% (3/9). Median PFS 7.3 months..

Changed Afatinib, Gefitinib, Erlotinib in Non-small cell lung cancer with EGFR A763_Y764insFQEA

Tier changed: 32. Comments changed: Not explicitly TGA listed. Comprehensive molecular profiling can identify uncommon EGFR mutations such as kinase domain duplications and rearrangements that are responsive to EGFR inhibitors in lung adenocarcinomas..

Changed Capmatinib in Non-small cell lung cancer with MET Amplification: 3

References changed: 32877583, 10.1200/JCO.2019.37.15_suppl.9004, 10.1200/JCO.2020.38.15_suppl.9509.

Changed Capivasertib in Solid tumours with AKT1 E17K: 4

Comments changed: Phase 1 Expansion cohort of AZD5363. Activity was seen in AKT1 E17K-mutant cancers (n=52) with median PFS of 5.5, 6.6, and 4.2 months in ER+ breast, gynecologic, and other solid tumors, respectively, and responses were associated with AKT1 E17K mutant allele imbalance and coincident PI3K pathway hotspot mutations.Phase 1 Expansion cohort data.

Changed Therapy in Solid tumours with AKT2 Oncogenic mutations: 4

Therapy changed: CCT128930, Uprosertib. Comments changed: Preclinical study. CCT128930, a novel AKT inhibitor, exhibited antiproliferative activity, inhibited AKT substrates phosphorylation, and caused G1 arrest in PTEN-null U87MG cells, with antitumor activity observed in U87MG and BT474 human breast cancer xenografts.. References changed: 21191045, 23795919.

Changed Crizotinib, Ceritinib, Brigatinib in Acute lymphoblastic leukaemia with ALK A348D, F856S: 4

Comments changed: Preclinical study. ALK mutations identified in leukemia patients were potently transforming and conferred sensitivity to ALK kinase inhibitors..

Changed Crizotinib, Alectinib in Solid tumours, Histiocytosis, Renal cell carcinoma with ALK Fusion: 4

Comments changed: Comprehensive genomic profiling of 114,200 clinical cases revealed ALK fusions in 0.8% of cases, with 22.9% of ALK fusions occurring in non-NSCLC tumors, which responded to anti-ALK targeted therapies..

Changed Brigatinib in Non-small cell lung cancer with ALK Fusion AND Amplification, L1196M, E1408V, T1151M: 4

Comments changed: Phase 1/2 and Phase 2 (ALTA) trials. Brigatinib showed substantial activity in crizotinib-resistant ALK+ NSCLC patients with ALK fusion-positive status (cORR 57%) and in those with secondary ALK mutations (cORR 50%), with complex mutation patterns associated with resistance in 25% of patients at end of treatment..

Changed Therapy in Inflammatory myofibroblastic tumour with ALK Fusions: 4

Therapy changed: Alectinib, Ceritinib. Comments changed: Case report. Dramatic response to alectinib observed in a patient with inflammatory myofibroblastic tumor harboring ALK fusion gene.. References changed: 28977547, 30790150, 31805529.

Changed Alectinib in Breast Cancer with ALK STRN-ALK fusion: 4

Comments changed: Case report. A patient with STRN-ALK fusion-positive breast cancer responded to alectinib, with initial partial response followed by mixed response and eventual progression at 2 months, highlighting the potential benefit of comprehensive genomic profiling in identifying actionable targets in advanced breast cancer.. References changed: 3442322810.1200/PO.21.00142.

Changed Ensartinib in Non-small cell lung cancer with ALK T1151, C1156Y, F1174C, F1174L, F1174V, G1269A, L1196M, S1206R: 4

Comments changed: Review. New generation anaplastic lymphoma kinase inhibitors in NSCLC, discussing the development of II and III generation TKIs to overcome acquired resistance to crizotinib and manage CNS localizations..

Changed Selumetinib in Low-grade serous ovarian cancer with BRAF Fusions: 4

Comments changed: Case report and genomic analysis. A patient with low-grade serous ovarian cancer experienced a complete and durable response to selumetinib, with tumour harbouring a 15-nucleotide deletion in MAP2K1 gene encoding MEK1, and 82% of 28 analysed tumours had ERK pathway-activating mutations, including BRAF fusions.Case report only.

Changed Selumetinib in Low-grade serous ovarian cancer with MAP2K1 : 4

Alterations changed: Q56_V60del, Negative regulatory domain deletionOncogenic mutations. Comments changed: Case report and genomic analysis. A patient with low-grade serous ovarian cancer experienced a complete and durable response to selumetinib, with tumour harbouring a 15-nucleotide deletion in MAP2K1 gene encoding MEK1, and 82% of 28 analysed tumours had ERK pathway-activating mutations, including BRAF fusions.Case report and retrospective analysis of exceptional responder only.

Changed Asciminib in Chronic myelogenous leukaemia with ABL1 A337V, P465S: R2

Comments changed: Preclinical and phase 1 studies showed that asciminib, an allosteric ABL1 inhibitor, targets both native and mutated BCR-ABL1, including the gatekeeper T315I mutant, and has distinct resistance mutations, including A337V and P465S, compared to catalytic-site ABL1 kinase inhibitors..

Changed Crizotinib in Non-small cell lung cancer with ALK Amplification: R2

Comments changed: Studies identified multiple mechanisms of resistance to ALK tyrosine kinase inhibitors, including secondary mutations in the ALK TK domain, ALK gene amplification, and aberrant activation of other kinases such as KIT and EGFR..

Changed Crizotinib in Neuroblastoma with ALK : R2

Alterations changed: F1174L, F1174V, AmplificationF1174L, Amplification. Comments changed: Phase 2 study. ADVL0912. Crizotinib showed limited activity in patients with ALK-aberrant relapsed/refractory neuroblastoma, with an ORR of 15%, and resistance was associated with specific ALK mutations such as F1174L and F1174V, and ALK amplification..

Changed Osimertinib in Non-small cell lung cancer with ALK Fusion: R2

Comments changed: Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy revealed EGFR T790M mutation (63%), MET amplification (5%), HER2 amplification (13%), and small cell transformation (3%) as resistance mechanisms, including ALK fusion as an off-target resistance mechanism.Off-target mechanism.

Changed Ceritinib in Non-small cell lung cancer with ALK I1151ins, L1152R, L1152P, C1156Y, C1156T, F1174C, F1174L, F1174V, G1202R, G1202del: R2

Comments changed: Targeting ALK TKIs is limited by resistance, with diverse mechanisms identified, informing novel therapeutic strategies, including development of inhibitors like JH-VIII-157-02 that overcome G1202R mutation.. References changed: 28050598, 28122866, 2656828928050598; 28122866; 26568289.

Changed Crizotinib in Solid tumours with ALK L1196M, C1156Y: R2

Comments changed: Preclinical study. CH5424802, a selective ALK inhibitor, demonstrated antitumor activity against cancers with ALK gene alterations and inhibited the resistant gatekeeper mutant ALK L1196M..

Changed Crizotinib in Anaplastic large cell lymphoma with ALK NPM-ALK fusion: R2

Comments changed: Review articles. ALK-rearranged malignancies and mechanisms of resistance to ALK tyrosine kinase inhibitors... References changed: 28050598, 2812286628050598; 28122866.

Changed Anti-androgen in Prostate cancer with AR Amplification: R2

Comments changed: Clinical cohort studies. Plasma DNA analysis demonstrates that androgen receptor (AR) gene aberrations, including copy number gain and point mutations (T878A, L702H, F876L, H874Y, T877A), are associated with resistance to abiraterone and enzalutamide in castration-resistant prostate cancer patients, predicting poor treatment outcomes and survival.. References changed: 25712683, 2653725825712683; 26537258.

Changed Fulvestrant in Breast cancer with ARID1A Oncogenic mutations: R2

Comments changed: Preclinical study. ARID1A inactivation determines resistance to ER degrader fulvestrant by promoting a switch from ER-dependent luminal cells to ER-independent basal-like cells, mediated by loss of ARID1A-dependent SWI/SNF complex targeting to luminal lineage-determining transcription factors..

Changed Olaparib in Pancreatic adenocarcinoma with ARID1A Oncogenic mutations: R2

Comments changed: Two Phase 2 studies of Olaparib in previously treated pancreatic cancer with BRCAness; DDR-GAs subset (N=24) had higher median PFS (5.7 months) and OS (13.6 months); ARID1A (N=3) was among the DDR-GAs identified.Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. ARID1A (N=3).

Changed Olaparib in Breast cancer with ATM Oncogenic mutations: R2

Comments changed: Phase 2 TBCRC048 study. Olaparib showed efficacy in metastatic breast cancer with gPALB2 (ORR 82%, median PFS 13.3 months) and sBRCA1/2 (ORR 50%, median PFS 6.3 months) mutations, but not in ATM or CHEK2 mutations alone.TBCRC048. No responders.

Changed Talazoparib in Lung squamous cell carcinoma with ATM Oncogenic mutations: R2

Comments changed: Lung-MAP Substudy S1400G. Phase 2. Talazoparib showed limited efficacy in homologous recombination repair-deficient squamous cell lung cancer with ORR of 4% in primary analysis population and 11% in full eligible population.Lung-MAP Substudy S1400G. ORR primary population 4%.

Changed Olaparib in Prostate cancer with ATM Oncogenic mutations: R2

Comments changed: Retrospective study. Men with metastatic castration-resistant prostate cancer harboring ATM mutations had inferior outcomes to olaparib treatment compared to those with BRCA1/2 mutations, with 0% PSA response (0/6) versus 76% (13/17) and median PFS 2.4 months versus 12.3 months.Retrospective study. ORR 0%.

Changed Olaparib in Prostate cancer with ATM Oncogenic mutations: R2

Comments changed: Updated: PROFOUND trial: No overall PFS difference in ATM subgroup, although benefits in patients previously treated with a taxane was noted (not sufficiently powered).Updated: PROFOUND trial: No overall PFS difference in , although benefits in patients previously treated with a taxane was noted (not sufficiently powered)..

Changed Talazoparib in Lung squamous cell carcinoma with ATR Oncogenic mutations: R2

Comments changed: Lung-MAP Substudy S1400G. Phase 2. Talazoparib showed limited efficacy in homologous recombination repair-deficient squamous cell lung cancer with ORR of 4% in primary analysis population and 11% in full eligible population.Lung-MAP Substudy S1400G. ORR primary population 4%.

Changed Olaparib, Talazoparib in Mesothelioma with BAP1 Loss-of-function mutations: R2

Comments changed: Preclinical study. Mesothelioma cells' sensitivity to PARP inhibitors is not dependent on BAP1 status, but is enhanced by temozolomide in cells with high Schlafen 11 and low O6-methylguanine-DNA methyltransferase expression, indicating a potential beneficial combination therapy for patients with specific tumor expression profiles.Preclinical data only.

Changed Niraparib in Solid tumours with BAP1 Oncogenic mutations: R2

Comments changed: Phase 2 trial. NCT03207347. Niraparib showed limited activity in patients with BAP1 with ORR of (1/18) 6% but clinical benefit was observed in 78% of patients with confirmed mBAP1 tumor, suggesting potential utility in DDR pathway-deficient neoplasms with confirmed mBAP1.Phase 2. NCT03207347. ORR was 1 of 18 responder (6%).. References changed: 39626160, 10.1200/JCO.2022.40.16_suppl.3122.

Changed Gefitinib, Erlotinib in Non-small cell lung cancer with BCL2L11 Deletion: R2

Comments changed: A common intronic deletion polymorphism in the BIM gene confers intrinsic resistance to tyrosine kinase inhibitors (TKIs) in CML and EGFR NSCLC by expressing BIM isoforms lacking the pro-apoptotic BH3 domain, leading to inferior responses to TKIs, but this resistance can be overcome with BH3-mimetic drugs..

Changed Larotrectinib in Low-grade spindle cell neoplasm, Solid tumour with BRAF BRAF-CREB3L2 rearrangement, amplification: R2

Comments changed: Case report. Off-target resistance mechanism identified in two pediatric patients with NTRK fusion-positive solid tumors treated with larotrectinib..

Changed Vemurafenib, Dabrafenib in Solid tumours with BRAF Class II mutations, K601E, K601N, K601T, L597Q, L597V, G469A, G469V, G469R, G464V, G464E, Fusions: R2

Comments changed: Preclinical study. Class 2 mutations shows insensitivity to Type 1 and half BRAF inhibitors.Class II mutations.

Changed Vemurafenib in Non-small cell lung cancer with BRAF Oncogenic mutations AND NOT V600: R2

Comments changed: Phase 2. AcSé. NCT02304809. BRAF(V600) mutated NSCLC patients treated with Vemurafenib showed an ORR of 44.9% and median PFS of 5.2 months, while BRAF(nonV600) mutated patients had an ORR of 0%.Phase 2. AcSé. NCT02304809. ORR: 0%..

Changed Vemurafenib in Colorectal adenocarcinoma with BRAF V600: R2

Comments changed: Phase 2 VE-BASKET trial. NCT01524978. Vemurafenib showed varying response rates across different BRAF V600 mutation-positive nonmelanoma cancers, with anecdotal responses observed in colorectal cancer patients treated with vemurafenib and cetuximab but not as a single-agent..

Changed Lapatinib + Trastuzumab in Colorectal adenocarcinoma with BRAF V600E: R2

Comments changed: Phase 2 HERACLES trial. EudraCT 2012-002128-33. In treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer, dual-targeted therapy with trastuzumab and lapatinib achieved an objective response in 30% of patients. No response in a patient with BRAF V600E co-mutation..

Changed Trastuzumab + Pertuzumab in Colorectal adenocarcinoma with BRAF V600E: R2

Comments changed: Phase 2a MyPathway study. NCT02091141. N=57. Pertuzumab + Trastuzumab showed an objective response in 32% of patients with HER2-amplified metastatic colorectal cancer, with one patient achieving complete response and 17 partial responses, indicating a potential therapeutic opportunity. A single patient with BRAF V600E co-mutation had no response..

Changed Trastuzumab in Gastric cancer with BRAF V600E: R2

Comments changed: Biomarkers study, Resistance mechanism to Trastuzumab in HER2-positive metastatic gastric cancer, including EGFR/MET/KRAS/PI3K/PTEN mutations and amplifications, predicted poor PFS (2.6 vs 5.2 months) and OS (7.6 vs 16.1 months).Case-control study.

Changed Sonidegib, Vismodegib in Solid tumours with BRAF V600E: R2

Comments changed: Preclinical study. RAS/MAPK pathway activation drives resistance to Smo inhibition and enhances metastatic behavior in Shh pathway-dependent tumors, with evidence of RAS/MAPK activation in secondary squamous cell cancers emerging from antecedent BCC tumors treated with Smo inhibitor.Off-target mechanism.

Changed Selumetinib in Melanoma with BRAF V600E and Amplification: R2

Comments changed: Preclinical study. BRAF gene amplification promotes acquired resistance to MEK inhibitors in BRAF V600E mutant cancer cells by increasing phosphorylated MEK abundance, and combined MEK and BRAF inhibition overcomes this resistance mechanism..

Monday, 2 June 2025 (Version: 20250602AU)

New Erlotinib, Osimertinib in Non-small cell lung cancer with BRAF Fusion, AGK-BRAF fusion, PJA2-BRAF fusion: R2

Preclinical study and genomic analysis of patient samples. BRAF fusions (AGK-BRAF and PJA2-BRAF) were identified as an off-target mechanism of acquired resistance to EGFR TKI therapy in approximately 2% of EGFR-mutant lung cancer patients, and combined inhibition of EGFR and MEK or BRAF inhibition were shown to be potential therapeutic strategies. References: 30831205

New Adagrasib + Pembrolizumab in Non-small cell lung cancer with KRAS G12C: 2

Phase 2 KRYSTAL-7 study. NCT04613596. N=149. Adagrasib plus pembrolizumab showed an ORR of 44.3% and median OS of 18.3 months in patients with advanced/metastatic KRASG12C-mutated NSCLC, with varying efficacy across different PD-L1 expression levels. References: 10.1200/JCO.2025.43.16_suppl.8500

New Benmelstobart + Anlotinib in Non-small cell lung cancer with CD274 Protein expression: 2

Phase 3. NCT04964479. In PD-L1 positive NSCLC patients, benmelstobart + anlotinib significantly improved PFS (11.0 vs 7.1 months) and ORR (57.3% vs 39.6%) compared to pembrolizumab, particularly in subgroups with squamous cell carcinoma and PD-L1 expression ≥50%. References: 10.1200/JCO.2025.43.16_suppl.LBA8502

New Trastuzumab deruxtecan in Non-small cell lung cancer with ERBB2 Overexpression, Amplification: 2

Phase 3 DESTINY-Gastric04 trial. NCT04704934. In HER2+ (IHC 3+ or IHC 2+/ISH+) unresectable/metastatic GC/GEJA patients, T-DXd showed significant improvement in OS (14.7 vs 11.4 months), PFS (6.7 vs 5.6 months), and confirmed ORR (44% vs 29%) over Ramucirumab + Paclitaxel. References: 10.1200/JCO.2025.43.16_suppl.LBA4002

New Zipalertinib in Non-small cell lung cancer with EGFR Exon 20 insertion: 2

Phase 2b REZILIENT1 study. Zipalertinib achieved a confirmed ORR of 35% and median PFS of 9.5 months in non-small cell lung cancer patients harboring EGFR exon 20 insertion mutations following prior platinum-based chemotherapy with or without amivantamab. References: 10.1200/JCO-25-00763, 10.1200/JCO.2025.43.16_suppl.8503

New Camizestrant + Palbociclib, Camizestrant + Ribociclib, Camizestrant + Abemaciclib in Breast cancer with ESR1 Oncogenic mutations, D538G, Y537S, Y537N: 2

Phase 3 SERENA-6 trial. NCT04964934. In patients with ER-positive, HER2-negative advanced breast cancer with emerged ESR1 mutation, switching to camizestrant with continued CDK4/6 inhibitor resulted in significantly longer PFS (16.0 months vs 9.2 months) compared to continuing aromatase inhibitor plus CDK4/6 inhibitor. References: 10.1200/JCO.2025.43.17_suppl.LBA4

New Sevabertinib in Non-small cell lung cancer with ERBB2 Oncogenic mutations, Tyrosine kinase domain mutations: 2

Phase 1/2 SOHO-01 trial. In patients with advanced HER2-mutant NSCLC, Sevabertinib demonstrated an ORR of 59% in both pretreated patients naive to HER2-targeted therapy and treatment-naive patients. References: 10.1200/JCO.2025.43.16_suppl.8504

New Savolitinib + Osimertinib in Non-small cell lung cancer with EGFR+MET EGFR:Oncogenic mutations and MET:amplification: 2

Phase 3 SACHI study. In EGFR-mutant, MET-amplified advanced NSCLC patients progressing on EGFR-TKI, savolitinib + osimertinib significantly improved PFS versus chemotherapy (8.2 vs 4.5 months, HR=0.34). MET amplification was defined as copy number ≥5 or MET/CEP7 ratio ≥2.0. References: 10.1200/JCO.2025.43.17_suppl.LBA8505

New Patritumab deruxtecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 3

Phase 3 HERTHENA-Lung02 trial. NCT05338970. N=586. Patritumab deruxtecan showed significant improvement in PFS (HR, 0.77) over platinum-based chemotherapy in EGFR-mutated NSCLC patients after disease progression on a 3rd-gen EGFR TKI, with median PFS 5.8 months vs 5.4 months. References: 10.1200/JCO.2025.43.16_suppl.8506

New Sacituzumab tirumotecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 2

Phase 2/3 OptiTROP-Lung03 trial. NCT05631262. In EGFR-mutated NSCLC patients previously treated with EGFR TKI and platinum-based chemotherapy, sacituzumab tirumotecan demonstrated superior efficacy versus docetaxel with ORR of 45.1% vs 15.6%, PFS of 6.9 vs 2.8 months, and OS HR of 0.49. References: 10.1200/JCO.2025.43.16_suppl.8507

Removed EGFR inhibitor in Non-small cell lung cancer with BRAF+EGFR alterations EGFR:Oncogenic mutations and BRAF:fusion: Tier R2

Changed Therapy in Non-small cell lung cancer with ERBB2 Oncogenic mutations: 3

Therapy changed: SevabertinibBAY 2927088. Comments changed: Phase 1/2 SOHO-01 study. NCT05099172. N=34. Sevabertinib led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months.Phase 1/2 SOHO-01 study. NCT05099172. N=34. BAY 2927088 led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months..

Changed Encorafenib + Capamatinib in Colorectal adenocarcinoma with BRAF+MET BRAF:V600E AND MET:amplification: 4

Comments changed: Case report. BRAF V600E-mutated metastatic colorectal cancer developed secondary resistance to cetuximab, encorafenib, and binimetinib due to MET amplification, and tertiary resistance to capmatinib and encorafenib due to emergence of MET D1228N mutation and KRAS G12D..

Changed Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+KRAS BRAF:V600E AND KRAS:G12D, BRAF:V600E AND KRAS:Oncogenic mutations: R2

Comments changed: Case report. BRAF V600E-mutated metastatic colorectal cancer developed secondary resistance to cetuximab, encorafenib, and binimetinib due to MET amplification, and tertiary resistance to capmatinib and encorafenib due to emergence of MET D1228N mutation and KRAS G12D..

Changed Dabrafenib + Trametinib in Non-small cell lung cancer with BRAF+KRAS BRAF:V600E AND KRAS:Q61R: R2

Comments changed: Phase 2 MATCH-R trial. Acquired resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R mutations, and PTEN frameshift mutation, highlighting MAPK pathway involvement..

Changed Dabrafenib + Trametinib in Non-small cell lung cancer with BRAF+MAP2K1 BRAF:V600E AND MAP2K1:K57N: R2

Comments changed: Phase 2 MATCH-R trial. Acquired resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R mutations, and PTEN frameshift mutation, highlighting MAPK pathway involvement..

Changed Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+MET BRAF:V600E AND MET:amplification: R2

Comments changed: Case report. BRAF V600E-mutated metastatic colorectal cancer developed secondary resistance to cetuximab, encorafenib, and binimetinib due to MET amplification, and tertiary resistance to capmatinib and encorafenib due to emergence of MET D1228N mutation and KRAS G12D..

Changed Dabrafenib + Trametinib in Non-small cell lung cancer with BRAF+NRAS BRAF:V600E AND NRAS:Q61R: R2

Comments changed: Novel resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R, and PTEN frameshift mutations, highlighting the recurring involvement of the MAPK pathway..

Changed Dabrafenib + Trametinib in Non-small cell lung cancer with BRAF+PTEN BRAF:V600E AND PTEN:Oncogenic mutations: R2

Comments changed: Novel resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R, and PTEN frameshift mutations, highlighting the recurring involvement of the MAPK pathway..

Changed Veliparib in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): R2

Comments changed: Phase 2 trial. In patients with pancreas adenocarcinoma and germline BRCA/PALB2 mutation, cisplatin and gemcitabine with or without veliparib showed high response rates (74.1% and 65.2% respectively), with no significant difference between the two arms, suggesting resistance to PARP inhibitor veliparib when used in combination with DNA damaging agents.Single-agent has no confirmed response.

Changed Palbociclib in Lung squamous cell carcinoma with CCND1 Amplification: R2

Comments changed: Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.Lung-MAP S1400C, ORR 6%.

Changed Palbociclib in Lung squamous cell carcinoma with CCND2 Amplification: R2

Comments changed: Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.Lung-MAP S1400C, ORR 6%.

Changed Palbociclib in Lung squamous cell carcinoma with CCND3 Amplification: R2

Comments changed: Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.Lung-MAP S1400C, ORR 6%.

Changed Palbociclib in Glioblastoma with CDK4 Amplification: R2

Comments changed: Preclinical study. GBM xenograft cells with p16(INK4a) expression and either CDK4 amplification or RB mutation were resistant to PD0332991, a Cdk4/6 inhibitor, indicating that intact p16-Cdk4-Rb axis is a determinant of resistance to Cdk4/6 inhibition..

Changed Palbociclib in Lung squamous cell carcinoma with CDK4 Amplification: R2

Comments changed: Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.Lung-MAP S1400C, ORR 6%.

Changed Larotrectinib in Low-grade glioma, Low-grade spindle cell neoplasm, Solid tumour with CDKN2A Deletion: R2

Comments changed: Case reports. Off-target resistance mechanism identified in two pediatric patients with NTRK fusion-positive solid tumors treated with larotrectinib..

Changed Trastuzumab in Gastric cancer with EGFR Amplification: R2

Comments changed: Case-control study. AMNESIA panel alterations, including EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications, were more frequent in HER2-positive metastatic gastric cancer patients resistant to trastuzumab, and absence of these alterations was associated with longer median PFS (5.2 vs 2.6 months) and OS (16.1 vs 7.6 months)..

Changed Cetuximab in Glioblastoma with EGFR Amplification: R2

Comments changed: Phase 2 trial of cetuximab in recurrent high-grade glioma showed limited activity, with 5.5% partial response rate and median PFS of 1.9 months, and no significant correlation was found between response and EGFR amplification, indicating potential resistance mechanism unrelated to EGFR gene copy number..

Changed Dacomitinib in Glioblastoma with EGFR Amplification: R2

Comments changed: Phase 2 trial of dacomitinib in recurrent glioblastoma with EGFR amplification showed limited single-agent activity, with a median PFS of 2.7 months and PFS6 of 10.6%.PFS6 10%.

Changed Gefitinib in Glioblastoma with EGFR Amplification: R2

Comments changed: Phase 2 trial evaluated gefitinib in newly diagnosed glioblastoma patients, showing no significant improvement in OS or PFS, with no correlation between EGFR status and clinical outcome, indicating potential resistance to gefitinib.No survival benefit.

Changed Larotrectinib in Low-grade glioma with EGFR Amplification: R2

Comments changed: Case reports. Off-target resistance mechanism identified in two pediatric patients with NTRK fusion-positive solid tumors treated with larotrectinib..

Changed Erlotinib in Colorectal adenocarcinoma with EGFR EGFR-SEPT14 Fusion: R2

Comments changed: Case report. A patient with colorectal adenocarcinoma harboring a rare EGFR-SEPT14 fusion achieved a partial response to erlotinib, but subsequently developed resistance with the emergence of EGFRvIII mutation..

Changed Vandetanib in Solid tumours with RET S904F: R2

Comments changed: Preclinical and clinical studies. Resistance mechanisms to RET inhibitors in RET-dependent cancers, including a secondary RET mutation S904F in the activation loop conferring resistance to vandetanib, and highlighted the need for next-generation RET inhibitors to overcome resistance..

Sunday, 1 June 2025 (Version: 20250601AU)

New Obrixtamig in Extrapulmonary neuroendocrine carcinoma with DLL3 High expression: 3

Phase 1 trial. NCT04429087. Obrixtamig showed greater efficacy in patients with extrapulmonary neuroendocrine carcinomas with high DLL3 expression (ORR: 40.0%, median DoR: 7.9 months) compared to those with low DLL3 expression (ORR: 3.3%). DLL3-high is defined as >50% TC. References: 10.1200/JCO.2025.43.16_suppl.3004

New BNT142 in Ovarian cancer, Solid tumours with CLDN6 Protein expression: 4

Phase 1/2 BNT142-01 trial. NCT05262530. N=65. BNT142 showed promising anti-tumor activity with 7 partial responses in ovarian cancer and a disease control rate of 58% across all dose levels in CLDN6+ advanced solid tumors. CLDN6 positivity is defined as ≥ membrane positivity in 10% of cell. No clear relationship beween CLDN6 expression level versus response seen. References: 10.1200/JCO.2025.43.16_suppl.2501

New 212Pb-VMT-alpha-NET in Neuroendocrine tumour with SSTR2 Protein expression: 4

Phase 1/2a study. NCT05636618. [212Pb]VMT-α-NET. 3/7 patients achieving partial responses at 185 MBq dose level in SSTR2-expressing neuroendocrine tumors. DOTATATE-positive. References: 10.1200/JCO.2025.43.16_suppl.3005

New Trametinib in Melanoma with BRAF K601, K601E: R2

Phase 2 NCI-MATCH trial. NCT02465060 (Subprotocol R). N=32. Trametinib showed limited activity with 3% ORR and 34% clinical benefit rate in patients with BRAF non-V600 mutations or fusions, with median PFS of 1.8 months and median OS of 5.7 months. References: 31924734

Removed Cobimetinib; Trametinib in Non-small cell lung cancer with MAP2K1 alterations Oncogenic mutations: Tier 4

Removed RO5045337 in Liposarcoma with MDM2 alterations Amplification: Tier 4

Removed Fulvestrant + Copanlisib in Breast cancer with PIK3CA alterations Oncogenic mutations: Tier 4

Removed AZD4547 in Lung squamous cell carcinoma with FGFR3 alterations Amplification, Fusion, S249C: Tier R2

Removed Ponatinib in Solid tumours with NRAS alterations Q61K: Tier R2

Changed Vandetanib in Non-small cell lung cancer with RET Fusions: 3

Comments changed: Phase 2 trial. N=18. Vandetanib showed an ORR of 18% and DCR of 65% in pretreated NSCLC patients with RET rearrangement, with a median PFS of 4.5 months and OS of 11.6 months.Not TGA approved. ORR 18%. OncoKB LOE 2.

Changed Sorafenib in Non-small cell lung cancer with ARAF S214C: 4

Comments changed: Case report and preclinical study. ARAF S214C mutation identified in a lung adenocarcinoma patient with a near-complete response to sorafenib, was shown to be oncogenic and sorafenib-sensitive in cellular transformation assays.Single case report. OncoKB LOE 3.

Changed Trametinib in Melanoma with BRAF K601, K601E: 4

Comments changed: Phase 2 trial of Trametinib in patients with metastatic BRAF-mutant melanoma. N=97. In BRAF-inhibitor naive patients (cohort B, N=57), ORR was 25% (1 CR, 13 PR), median PFS 4.0 months, and median OS 14.2 months. One patient with BRAF K601E mutation had a confirmed PR with PFS of 32 weeks.Case reports only; OncoKB LOE 3. References changed: 23248257; 31924734.

Changed Cobimetinib, Trametinib with MAP2K1 Oncogenic mutations: 4

Cancer type(s) changed: Melanoma, Non-small cell lung cancer Comments changed: Trametinib showed activities in treating cell lines or patients with MEK1 mutations across various malignancies, suggesting MEK1 mutations as potential indications for trametinib therapy, although resistance was observed with varying responses to different MEK1 mutations.OncoKB LOE 3.

Changed Therapy in Solid tumours with MAP2K1 Oncogenic mutations: 4

Therapy changed: UlixertinibMEK inhibitor, ERK inhibitor. Comments changed: Preclinical study. ERK inhibitor ulixertinib showed therapeutic potential against BRAF mutant, BRAF-MEK inhibitor resistant, or RAS mutant tumors with clinical activity against various tumor types in a first-in-human dose-escalation study..

Changed Trametinib in Glioblastoma, Type 1 neurofibromatosis with NF1 Oncogenic mutations: 4

Comments changed: Case report. Treatment-refractory neurofibromatosis-associated glioblastoma experienced clinical and radiological benefit from the MEK inhibitor, trametinib.OncoKB LOE 3, case report only.

Changed GDC-0077 in Breast cancer with PIK3CA Oncogenic mutations: 4

Comments changed: Phase 1a dose escalation study. NCT03006172. N=20. GDC-0077, a p110α-selective and mutant-degrading PI3K inhibitor, showed manageable safety profile, linear PK, and preliminary anti-tumor activity with 25% partial response rate and 45% clinical benefit rate in patients with PIK3CA-mutant solid tumors.Phase 1. NCT03006172. First-in-human ORR confirmed PR in 4 pts (20%). Clinical benefit rate was 45%; OncoKB LOE 3.

Changed Capmatinib, Crizotinib in Non-small cell lung cancer with EGFR Amplification: R2

Comments changed: Preclinical and clinical genomic analysis identified on-target MET kinase domain mutations and off-target mechanisms including KRAS mutations and amplifications in KRAS, EGFR, HER3, and BRAF as drivers of resistance to MET TKIs in MET exon 14-mutant NSCLC.Off-target resistance.

Changed Capmatinib in Non-small cell lung cancer with ERBB3 Amplification: R2

Comments changed: Preclinical and clinical genomic analysis identified on-target MET kinase domain mutations and off-target mechanisms including KRAS mutations and amplifications in KRAS, EGFR, HER3, and BRAF as drivers of resistance to MET TKIs in MET exon 14-mutant NSCLC.Off-target resistance.

Changed Lapatinib in Breast cancer with ERBB3 F94L, G284R, D297Y, T355I, E1261A: R2

Comments changed: Preclinical study. HER3 mutations (e.g., T355I, F94L, G284R, D297Y, E1261A) were found to be activating and confer resistance to lapatinib in ER+ and HER2+ breast cancer cells, with HER3(T355I) inducing cell proliferation via HER4/HER1-dependent ERK1/2 and cyclinD1 mediated pathways.In ER-positive HER2-positive cell line.

Changed Fulvestrant in Breast cancer with ESR1 ESR1-YAP1 fusion, ESR1-PCDH11X fusion, ESR1-SOX9 fusion, ESR1-ARNT2 fusion: R2

Comments changed: Preclinical study. Functionally active ESR1 gene fusions and activating ESR1 LBD point mutations drives endocrine treatment failure and resistance in metastatic breast cancer..

Changed Tamoxifen, Letrozole, Fulvestrant in Breast cancer with ESR1 Fusion, ESR1-YAP1 fusion, ESR1-PCDH11X fusion: R2

Comments changed: Preclinical study. ESR1 gene fusions (e.g., ESR1-e6>YAP1 and ESR1-e6>PCDH11X) confer estrogen-independent growth, anti-estrogen resistance, and metastatic progression in ER-positive breast cancer, although remaining sensitive to CDK4/6 inhibitors..

Changed Pembrolizumab in Melanoma with FBXW7 Loss-of-function mutations, R505: R2

Comments changed: Preclinical studies. Inactivation of Fbxw7 impairs dsRNA sensing and confers resistance to PD-1 blockade through downregulation of viral sensing pathways, including decreased expression of MDA5 and RIG1, and diminished type I IFN and MHC-I expression..

Changed AZD4547 in Lung squamous cell carcinoma with FGFR1 Alteration: R2

Comments changed: Phase 2 Lung-MAP S1400D substudy. AZD4547 targeting FGFR alteration showed minimal activity with ORR (1/27) 7% and median PFS of 2.7 months in previously treated FGFR-altered squamous NSCLC..

Changed Fulvestrant + Palbociclib, Fulvestrant + Ribociclib in Breast cancer with FGFR1 Amplification: R2

Comments changed: FGFR1 amplification mediates endocrine resistance in ER+ breast cancer by conferring broad resistance to ER, PI3K, and CDK4/6 inhibitors, but retains sensitivity to mTOR inhibitors, suggesting a potential therapeutic role for mTOR inhibitors in ER+/FGFR1+ MBC..

Changed AZD4547 in Lung squamous cell carcinoma with FGFR1 Amplification: R2

Comments changed: Phase 2 Lung-MAP S1400D substudy. AZD4547 targeting FGFR alteration showed minimal activity with ORR (1/27) 7% and median PFS of 2.7 months in previously treated FGFR-altered squamous NSCLC.SWOG S1400D; Minimal response (1/27).

Changed AZD4547 in Lung squamous cell carcinoma with FGFR3 : R2

Alterations changed: Amplification, Fusion, S249CAlteration. Comments changed: Phase 2 Lung-MAP S1400D substudy. AZD4547 targeting FGFR alteration showed minimal activity with ORR (1/27) 7% and median PFS of 2.7 months in previously treated FGFR-altered squamous NSCLC..

Changed Nilotinib in Melanoma with KIT Amplification: R2

Comments changed: Phase 2 UN10-06 trial. Nilotinib in metastatic melanoma with KIT gene aberrations showed durable response in a subset of patients with specific KIT mutations in exons 11 and 17, although the primary endpoint of response rate was not met. In the KIT amplification only subgroup, 1/15 patients responded (ORR 6%) with a duration of response of 5 weeks. Gene co-mutation status was not available.Phase 2 UN10-06 trial. In KIT amplification only subgroup, only 1/15 response with with DOR of 5 weeks only (ORR 6%). Gene co-mutation status was not available in the case..

Changed Imatinib, Sunitinib, Regorafenib in Gastrointestinal stromal tumour with KIT D816V: R2

Comments changed: Preclinical studies and case reports. Type II c-Kit inhibitors such as BLU-285 inhibit activation loop mutants including KIT D816V and PDGFRA D842V mutations, demonstrating activity in phase 1 studies in patients with KIT/PDGFRA-driven cancers.Preclinical studies and case reports. Type II c-Kit inhibitors are sensitive to KIT D816 and PDGFR842V mutations.

Changed Axitinib in Gastrointestinal stromal tumour with KIT D816V, D816H, D816: R2

Comments changed: Preclinical study. Axitinib showed potent activity against various cKIT primary and secondary mutations, including imatinib-resistant mutations T670I and V654A, in GIST preclinical models and patient-derived primary cells, but lacked activity in D816..

Changed Sunitinib in Gastrointestinal stromal tumour with KIT K642E, D816V, D820A, D816: R2

Comments changed: Preclinical and biomarker studies. Investigations into KIT mutations and resistance mechanisms revealed that midostaurin and avapritinib exhibit distinct resistance profiles, with T670I gatekeeper mutation conferring avapritinib resistance, and that ripretinib, a switch-control kinase inhibitor, broadly inhibits KIT and PDGFRA mutants, while rapid alternation of sunitinib and regorafenib suppresses growth of polyclonal imatinib-resistant GIST.Primary GIST resistance.

Changed Sunitinib in Gastrointestinal stromal tumour with KIT R796G, C809G, D816F, D816G, D816H, D816V, D816, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840N: R2

Comments changed: Preclinical studies investigated secondary resistance mechanisms in KIT-mutant GIST, identifying distinct resistance profiles for ATP-competitive inhibitors midostaurin and avapritinib, and demonstrating the potential of combining TKIs with complementary activity against resistant mutations to suppress growth of polyclonal imatinib-resistance..

Changed Imatinib in Melanoma with KIT : R2

Alterations changed: A829P, T670I. Comments changed: Preclinical study. Secondary c-Kit mutations (A829P and T670I) confer acquired resistance to RTK inhibitors (imatinib and nilotinib) in c-Kit mutant melanoma cells, but alternative RTK inhibitors (dasatinib and sunitinib) or combined inhibition of MAPK and PI3K pathways may overcome this resistance.Not TGA approved..

Changed Regorafenib in Gastrointestinal stromal tumour with KIT V654A, D816V, D816: R2

Comments changed: Preclinical studies. Secondary kinase domain mutations in KIT as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in GIST, with distinct resistance profiles observed for midostaurin and avapritinib, and ripretinib showing broad spectrum inhibition of oncogenic and drug-resistant KIT and PDGFRA variants.Secondary resistance.

Changed Imatinib in Gastrointestinal stromal tumour with KIT V654A, N655S, T670I, N680K, F681L, C809G, D816G, D816H, D816V, D816, D820G, D820E, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840N: R2

Comments changed: Preclinical studies. Secondary kinase domain mutations in KIT as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in GIST, with distinct resistance profiles observed for midostaurin and avapritinib, and ripretinib showing broad spectrum inhibition of oncogenic and drug-resistant KIT and PDGFRA variants.Secondary resistance.

Changed Avapritinib in Gastrointestinal stromal tumour with KIT V654A, N655S, T670I, N822T, S840N: R2

Comments changed: Preclinical studies. Secondary kinase domain mutations in KIT as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in GIST, with distinct resistance profiles observed for midostaurin and avapritinib, and ripretinib showing broad spectrum inhibition of oncogenic and drug-resistant KIT and PDGFRA variants.Secondary resistance.

Changed Crizotinib in Non-small cell lung cancer with MET F1007fs (F1025fs): R2

Comments changed: Case report. Novel MET Exon 14 skipping treatment-naive lung adenocarcinoma presented primary resistance to crizotinib.Case report. Primary resistance to crizotinib.

Changed Vandetanib, Cabozantinib in Solid tumours with RET V804L, V804M: R2

Comments changed: Preclinical study. RET(V804L) and RET(G810A) gatekeeper mutations confer resistance to RET inhibitors, but can be overcome by next-generation inhibitors such as ponatinib and lenvatinib.

Changed Crizotinib in Non-small cell lung cancer with ROS1 E1395G, L1947R, G1971E, S1986Y, S1986F, L2026M, G2032R, D2033N, S2060G, V2098U, L2155S: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed Cabozantinib in Non-small cell lung cancer with ROS1 F2004C, F2075V, D2113G: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed Lorlatinib in Non-small cell lung cancer with ROS1 G2032R: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed Crizotinib, Entrectinib, Loratinib in Solid tumours with ROS1 G2032R: R2

Comments changed: Preclinical study. ROS1 fusions and secondary resistance mutationsof earlier-generation TKIs..

Changed Ensartinib in Non-small cell lung cancer with ROS1 G2032R, D2033N: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed Ceritinib in Non-small cell lung cancer with ROS1 L1951R, G2032R, D2033N, G2101A, L2155S: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed Brigatinib in Non-small cell lung cancer with ROS1 L1951R, L2026M, G2032R, D2033N: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed AZD3463 in Non-small cell lung cancer with ROS1 L2026M, G2032R: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed Entrectinib in Non-small cell lung cancer with ROS1 L2026M, G2032R, D2033N: R2

Comments changed: Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains..

Changed Vismodegib, Sonidegib in Basal cell carcinoma, Solid tumours with SMO D473G, D473Y, D473H, G497W, V321M, W281L, Q477E, A327P, C390R, D506N, E181K, E481G, G453D, K519R, K564E, L221P, L353F, N476K, P513L, P698T, P739L, P739S, R168H, R199Q, T336I, T349I, T349P, T534I, T548I, T640A, V386A, V404M, V414A, A459V, D384N, E518K, I408V, N219D, S387N, T241M, V281C: R2

Comments changed: Preclinical and clinical studies demonstrated hedgehog signaling inhibitors' activity in various solid and hematological cancers, including pancreatic cancer, medulloblastoma, and leukemia, with SMO mutations identified as a key resistance mechanism in basal cell carcinoma.On-target resistance.

Changed Vismodegib in Medulloblastoma with SMO D473H: R2

Comments changed: Preclinical study. Genomic analysis of basal cell carcinoma tumor biopsies revealed On-target resistance to vismodegib associated with Hedgehog pathway reactivation through SMO mutation and SUFU and GLI2 copy number changes..

Changed Vismodegib in Basal cell carcinoma with SUFU Loss-of-function mutations: R2

Comments changed: Preclinical study. Genomic analysis of basal cell carcinoma tumor biopsies revealed vismodegib resistance associated with Hedgehog pathway reactivation through SMO mutation and SUFU and GLI2 copy number changes, suggesting combination therapies targeting multiple levels of the Hedgehog pathway may overcome resistance.Xenografts models of Sufu tumors showed resistance to SMO inhibition..

Saturday, 31 May 2025 (Version: 20250531AU)

New Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF V600E: 2

Phase3 BREAKWATER trial. NCT04607421. N=637. Encorafenib + cetuximab + mFOLFOX6 demonstrated significant improvement in PFS (12.8 vs 7.1 months) and OS (30.3 vs 15.1 months) compared to standard of care in BRAF V600E-mutant metastatic colorectal cancer. References: 10.1200/JCO.2025.43.16_suppl.LBA3500

New Olaparib, Talazoparib, Niraparib, Rucaparib in Uterine leiomyosarcoma with BRCA2 Oncogenic mutation, Deletion: 3

Retrospective analysis of 35 patients with BRCA-altered uterine sarcoma. N=13 treated with PARPis in recurrent/metastatic setting. ORR was 46% (1 CR, 5 PR). CBR was 62%. Median PFS was 13.2 months. Median PFS ratio compared to previous systemic therapy was 1.9. 60% ORR observed in patients with BRCA2 homozygous deletions. References: 40117531

New DB-1310 in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 3

Phase 1/2a trial. DB-1310, a HER3-targeted ADC, showed antitumor activity in heavily pretreated EGFRm NSCLC, with unconfirmed ORR of 44% (20/46) and median PFS of 7.0 months. References: 10.1200/JCO.2025.43.16_suppl.3000

New Datopotamab Deruxtecan in Non-small cell lung cancer with EGFR Exon 19 deletion, T790M, L858R, G719, L861Q, Exon 20 insertion mutations: 3

Phase 2 TROPION-Lung05 trial. NCT04484142. N=137. Dato-DXd showed an ORR of 35.8% in heavily pretreated NSCLC with actionable genomic alterations, with median DOR of 7.0 months. References: 39761483

New Patritumab deruxtecan in Non-small cell lung cancer with EGFR Exon 19 deletion,L858R: 3

Phase 2 HERTHENA-Lung01 trial. NCT04619004. N=225. Patritumab Deruxtecan (HER3-DXd) showed a confirmed ORR of 29.8% with median DOR of 6.4 months, median PFS of 5.5 months, and median OS of 11.9 months in patients with EGFR-mutated NSCLC previously treated with EGFR TKI and platinum-based chemotherapy. References: 37689979

New Izalontamab brengitecan in Non-small cell lung cancer with EGFR Oncogenic mutation and NOT Exon 19 deletion and NOT L858R, Exon 20 insertion: 3

Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 69% and mPFS of 7.0 months. References: 10.1200/JCO.2025.43.16_suppl.3001

New Izalontamab brengitecan in Non-small cell lung cancer with ERBB2 Oncogenic mutation: 3

Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 53%, DCR 100%, and mPFS of 7.5 months. References: 10.1200/JCO.2025.43.16_suppl.3001

New TQB2102 in Colorectal adenocarcinoma with ERBB2 Overexpression: 3

Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). References: 10.1200/JCO.2025.43.16_suppl.3002

New TQB2102 in Gastric cancer with ERBB2 Overexpression: 3

Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). References: 10.1200/JCO.2025.43.16_suppl.3002

New TQB2102 in Solid tumours with ERBB2 Overexpression: 3

Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). References: 10.1200/JCO.2025.43.16_suppl.3002

New TQB2102 in Breast cancer with ERBB2 Overexpression, Protein expression, Low-protein expression: 3

Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). References: 10.1200/JCO.2025.43.16_suppl.3002

New MK-1084, MK-1084 + Cetuximab in Colorectal adenocarcinoma with KRAS G12C: 3

Phase 1 KANDLELIT-001 trial. NCT05067283. MK-1084, a KRAS G12C inhibitor, showed antitumor activity in patients with advanced KRAS G12C-mutated CRC, with ORR of 36% as monotherapy, 50% with cetuximab, and 14% with cetuximab + mFOLFOX6. References: 10.1200/JCO.2025.43.16_suppl.3508

New Olomorasib + Cetuximab in Colorectal adenocarcinoma with KRAS G12C: 3

Phase 1/2 study. NCT04956640. N=93. Olomorasib + cetuximab showed an ORR of 42% and mPFS of 7.5 months in patients with KRAS G12C-mutant CRC, with a favorable safety profile and optimal dose of olomorasib determined as 100 mg BID. References: 10.1200/JCO.2025.43.16_suppl.3507

New Sotorasib + Panitumumab in Colorectal adenocarcinoma with KRAS G12C: 3

Phase 1b CodeBreaK 101 trial. NCT04185883. N=40. Sotorasib + panitumumab + FOLFIRI showed promising efficacy in pretreated KRAS G12C-mutated mCRC with ORR of 57.5%, median PFS of 8.2 months, and median OS of 17.9 months. References: 10.1200/JCO.2025.43.16_suppl.3506

New Izalontamab brengitecan in Non-small cell lung cancer with KRAS Oncogenic mutation, G12C: 3

Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months. References: 10.1200/JCO.2025.43.16_suppl.3001

New Izalontamab brengitecan in Non-small cell lung cancer with MET Exon 14 deletion, Exon 14 splicing mutation,: 3

Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months. References: 10.1200/JCO.2025.43.16_suppl.3001

New Izalontamab brengitecan in Non-small cell lung cancer with ALK Fusion: 4

Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months. References: 10.1200/JCO.2025.43.16_suppl.3001

New Olaparib + Temozolomide in Uterine leiomyosarcoma with RAD51 Loss of protein expression: 4

Phase 2 study. NCI Protocol 10250. N=22. Olaparib + temozolomide showed an ORR of 27% and mPFS of 6.9 months in advanced uterine leiomyosarcoma. 50% of tumors were homologous recombination-deficient by RAD51 assay, with prolonged mPFS (11.2 vs 5.4 months) in RAD51-deficient tumors. The RAD51 status is determined using a IHC based foci formation assay. References: 37467452

New Izalontamab brengitecan in Non-small cell lung cancer with RET Fusion: 4

Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months. References: 10.1200/JCO.2025.43.16_suppl.3001

New Izalontamab brengitecan in Non-small cell lung cancer with ROS1 Fusion: 4

Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months. References: 10.1200/JCO.2025.43.16_suppl.3001

Changed Therapy in Solid tumours with EGFR+ERBB3 EGFR:Protein expression AND ERBB3:Protein expression: 3

Therapy changed: Izalontamab brengitecan.

Changed Therapy in Urothelial carcinoma with EGFR+ERBB3 EGFR:Protein expression AND ERBB3:Protein expression: 3

Therapy changed: Izalontamab brengitecan.

Wednesday, 28 May 2025 (Version: 20250528AU)

New Vemurafenib + Cobimetinib in Solid tumours, Non-small cell lung cancer with BRAF V600E: 3

Phase 2 trial. MoST substudy 12. ACTRN12620000861954. N=64. VEM+COB achieved ORR of 50% in refractory BRAF V600-mutated solid tumours and 42% in 1L NSCLC, with median PFS of 7.9 months and OS of 15.9 months in solid tumour group, and 6-mo PFS rates of 68% and 67% in solid and 1L NSCLC groups respectively. References: 10.1016/j.annonc.2024.08.690

New Osimertinib + Crizotinib in Non-small cell lung cancer with EGFR+MET EGFR:T790M and MET:amplification: 4

Case report. EGFR-mutant NSCLC patient with emergent MET amplification after disease progression on erlotinib had a sustained partial response to combination osimertinib and crizotinib, with MET amplification persisting as a resistance mechanism at CNS progression. References: 30881166

New GQ1001 in Solid tumour with ERBB2 Overexpression, Amplification: 4

Phase Ia study. NCT04450732. GQ1001, a HER2-targeting ADC, showed promising antitumor activity in HER2-positive advanced solid tumors, with 6 out of 15 evaluable subjects achieving confirmed partial response at doses ≥ 7.2 mg/kg, and a median progression-free survival of 4.8 months. References: 10.1158/1538-7445.AM2023-CT178

New Palazestrant in Breast cancer with ESR1 Protein expression, Oncogenic mutations: 4

Phase 1b/2 study. NCT0526610. N=33. Palazestrant + Palbociclib were well tolerated with 55% grade 3 and 9% grade 4 neutropenia. 4 partial responses (2 confirmed) out of 19 response-evaluable patients with a CBR of 42% across all patients and 67% in patients with ESR1 mutations. References: 10.1158/1538-7445.SABCS23-PS15-04

New Palazestrant in Breast cancer with ESR1 Protein expression, Oncogenic mutations, Y537S, D538G: 4

Preclinical study. Palazestrant (OP-1250), a novel oral complete estrogen receptor antagonist, demonstrated superior efficacy and pharmacokinetic properties compared to fulvestrant, elacestrant, and tamoxifen in ER-positive breast cancer models, including wild-type and ESR1-mutant xenografts and intracranial implants. Updated: 2025-05-28. References: 38102750

New Talazoparib in Pancreatic adenocarcinoma with PALB2 Loss-of-function mutations: 4

Phase 1 trial. NCT01286987. Talazoparib demonstrated antitumour activity in a single case of PALB2 mutation amongst 13 pancreatic cancer patients who showed partial responses. References: 28242752

New Osimertinib in Non-small cell lung cancer with EGFR L747P: R2

Case report. A Chinese woman with stage IV lung adenocarcinoma harboring a rare EGFR L747P mutation showed intrinsic resistance to both gefitinib and osimertinib, highlighting the challenges in treating NSCLC with rare EGFR mutations. References: 29673089

New Osimertinib + Crizotinib in Non-small cell lung cancer with EGFR+MET EGFR:Exon 19 deletion and MET:Exon 14 skipping mutation, EGFR:L858R and MET:Exon 14 skipping mutation: R2

Preclinical study. Acquired MET exon 14 alteration drives secondary resistance to EGFR tyrosine kinase inhibitor in EGFR-mutated lung cancer. References: 31157314

New Trastuzumab in Extramammary Paget’s disease with ERBB3 A232V: R2

Case report. A patient with ERBB2(S310F) mutated metastatic extramammary Paget's disease initially responded to trastuzumab and carboplatin, but developed resistance with additional genomic alterations including ERBB3(A232V) and PIK3CA(G106V) mutations and MET and CDK6 amplification. References: 31803359

New AZD4547 in Solid tumours with FGFR1 Amplification, Oncogenic mutations: R2

Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions. References: 32463741, 10.1200/JCO.2018.36.15_suppl.2503

New Trametinib in Melanoma with MAP2K2 Q60P: R2

Preclinical study. Concurrent MEK2-Q60P mutation and BRAF amplification/V600E were identified in melanoma cells resistant to BRAF and MEK inhibitors, conferring sustained MAPK activation and on-target resistance, which was addressed by a triple combination of dabrafenib, trametinib, and GSK2126458. References: 24055054

New Trastuzumab in Extramammary Paget’s disease with MET Amplification: R2

Case report. A patient with ERBB2(S310F) mutated metastatic extramammary Paget's disease initially responded to trastuzumab and carboplatin, but developed resistance with additional genomic alterations including ERBB3(A232V) and PIK3CA(G106V) mutations and MET and CDK6 amplification. References: 31803359

Removed OP-1250 in Breast cancer with ESR1 alterations Oncogenic mutations, Protein expression: Tier 4

Removed Erdafitinib in Non-small cell lung cancer with FGFR2 alterations FGFR2-BICC1 fusion: Tier 4

Removed AMG-193 in Solid tumours with MTAP alterations Deletion: Tier 4

Removed GSK3368715 in Solid tumours with MTAP alterations Deletion: Tier 4

Removed Sorafenib in Gastrointestinal stromal tumour with KIT alterations D816H, D816V: Tier R2

Removed Lapatinib + Trastuzumab in Colorectal adenocarcinoma with KRAS alterations Oncogenic mutations: Tier R2

Removed Trastuzumab in Breast cancer with MET alterations Overexpression: Tier R2

Changed Binimetinib + Encorafenib in Melanoma with BRAF V600E, V600K: 1

Comments changed: TGA approved. PBS reimbursed. Phase 3 COLUMBUS trial. NCT01909453. Median overall survival was significantly longer with encorafenib plus binimetinib (33.6 months) compared to vemurafenib (16.9 months) in patients with BRAF(V600)-mutant melanoma.TGA approved. PBS reimbursed. COLUMBUS trial..

Changed Dostarlimab in Endometrial cancer with Mismatch repair Deficient

Tier changed: 12. Comments changed: TGA approved. PBS reimbursed. FDA approved. Phase 1 trial. GARNET. NCT02715284. N=71. Dostarlimab demonstrated an objective response rate of 42.3-43% (30 patients) with 12.7-13% complete response and 29.6% partial response in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) endometrial cancer as assessed by IHC, PCR, or NGS. Duration of response was 96.4% at 6 months and 76.8% at 12 months with an acceptable safety profile.GARNET trial: dMMR as assessed by IHC or MSI-H by PCR or NGS. ORR 43% with 13% CR. Duration of response at 6 months: 96%. FDA approved..

Changed Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Mismatch repair Deficient

Tier changed: 12. Comments changed: TGA approved. PBS reimbursed. Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. OS at 24 months was 83% with dostarlimab and 59% with placebo..

Changed Lu-177 vipivotide tetraxetan in Prostate cancer with PSMA Protein expression: 1B

Comments changed: TGA approved. FDA approved 2022-03-24. Phase 3 VISION trial. NCT03511664. N=831. Lutetium-177-PSMA-617 plus standard care significantly prolonged PFS (8.7 vs 3.4 months, HR 0.40) and OS (15.3 vs 11.3 months, HR 0.62) in patients with PSMA-positive (Gallium-68 positive) metastatic castration-resistant prostate cancer.TGA approaved. FDA approved 2022-03-24. Phase 3 VISION trial. NCT03511664. N=831. Lutetium-177-PSMA-617 plus standard care significantly prolonged PFS (8.7 vs 3.4 months, HR 0.40) and OS (15.3 vs 11.3 months, HR 0.62) in patients with PSMA-positive (Gallium-68 positive) metastatic castration-resistant prostate cancer..

Changed Capivasertib + Fulvestrant in Breast cancer with AKT1 Oncogenic mutation: 2

Comments changed: Not TGA approved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy.Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy..

Changed Sorafenib in Gastrointestinal stromal tumour with KIT Oncogenic mutations, V654A, T670I, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P: 2

Comments changed: Not TGA approved. Not FDA approved. NCCN recommended 2A. Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842.Not TGA approved; Not FDA approved. NCCN recommended 2A.

Changed Ibrutinib in Waldenstroms macroglobulinaemia with MYD88 Oncogenic mutations, L265P: 2

Comments changed: Phase 2 study. NCT01614821. N=63. Ibrutinib demonstrated high activity in pretreated Waldenstrom's macroglobulinemia patients with an overall response rate of 91% and major response rate of 73%. Patients with MYD88(L265P)CXCR4(WT) mutations achieved the highest response rates at 100% overall response and 91% major response..

Changed Pimitespib in Gastrointestinal stromal tumour with PDGFRA Oncogenic mutations: 2

Comments changed: Phase 3. CHAPTER-GIST-301. Phase 3 CHAPTER-GIST-301 trial. N=86. Pimitespib significantly improved PFS (2.8 months vs 1.4 months) and cross-over-adjusted OS (13.8 vs 9.6 months) compared with placebo in patients with advanced GIST refractory to standard TKIs. Single-agent Pimitespib was effective in treat-refractory GIST patients after imatinib, sunitinib, and regorafenib failure, including those with secondary KIT resistance..

Changed Capivasertib + Fulvestrant in Breast cancer with PIK3CA Oncogenic mutation: 2

Comments changed: Not TGA approved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy.Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy..

Changed Capivasertib + Fulvestrant in Breast cancer with PTEN Loss-of-function mutations, deletion: 2

Comments changed: Not TGA approved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy.Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy..

Changed Dasatinib in Acute lymphoblastic leukaemia, Chronic myelogenous leukaemia with ABL1 E255K, E255V, F359C, F359I, F359V, Y253H, A337V, P465S

Tier changed: 32.

Changed Bosutinib in Acute lymphoblastic leukaemia, Chronic myelogenous leukaemia with ABL1 E255K, E255V,F317C, F317I, F317L, F317V, F359C, F359I, F359V, T315A, Y253H, A337V, P465S

Tier changed: 32. Comments changed: Phase 3 BFORE trial. NCT02130557. Bosutinib demonstrated significantly higher MMR rate at 12 months (47.2% vs 36.9%) and CCyR rate by 12 months (77.2% vs 66.4%) compared to imatinib in patients with newly diagnosed chronic-phase CML.BCR-ABL1 fusion required, and not TGA approved by biomarker. OncoKB LOE 1.

Changed Nilotinib in Acute lymphoblastic leukaemia, Chronic myelogenous leukaemia with ABL1 F317C, F317I, F317L, F317V, T315A, V299L, A337V, P465S

Tier changed: 32. Comments changed: Phase 3 trial. NCT00471497. N=846. Nilotinib (300mg or 400mg twice daily) showed higher major molecular response rates (44% and 43% vs 22%) and complete cytogenetic response rates (80% and 78% vs 65%) compared to imatinib (400mg once daily) in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML.BCR-ABL1 fusion required, and not TGA approved by biomarker. OncoKB LOE 1.

Changed Imatinib in Acute lymphoblastic leukaemia, Chronic myelogenous leukaemia with ABL1 V299L, A337V, P465S

Tier changed: 32. Comments changed: Randomised study. N=1106. Imatinib showed superior major cytogenetic response (87.1% vs 34.7%), complete cytogenetic response (76.2% vs 14.5%), and freedom from progression to accelerated-phase or blast-crisis CML (96.7% vs 91.5%) compared to interferon alfa plus low-dose cytarabine in newly diagnosed chronic-phase CML. BCR-ABL1 fusion required, and not TGA approved by biomarker.BCR-ABL1 fusion required, and not TGA approved by biomarker. Adapted from APAR..

Changed Ponatinib in Acute lymphoblastic leukaemia, Chronic myelogenous leukaemia with ABL1 Y253H, E255K, E255V, V299L, F317L, F317C, F317I, F317V, F359C, F359V, F359I, A337V, P465S

Tier changed: 32.

Changed Durvalumab + Olaparib in Breast cancer with BRCA1 Oncogenic mutations (germline): 3

Comments changed: Phase 1/2 MEDIOLA trial. NCT02734004. N=34. Olaparib + durvalumab demonstrated antitumour activity in breast cancer patients (TNBC and non-TNBC) with maximum two prior treatment lines. In germline BRCA-mutated metastatic breast cancer, ORR was 63% with 80% disease control rate at 12 weeks and 50% at 28 weeks. PD-L1 status (1% threshold) was not significant.MEDIOLA breast cancer cohort, including both TNBC and non-TNBC. Maximum of two lines of prior treatments. ORR 63%. DCR 28 weeks: 50%. Note: PD-L1 (at 1%) status NS..

Changed Afatinib in Non-small cell lung cancer with ERBB2 A775_G776insYVMA (Y772_A775dup), M774dup: 3

Comments changed: Global named patient use program. N=28. Heavily pretreated ERBB2 mutation-positive NSCLC. Afatinib showed activity with ORR of 19% (3/16) with DCR of 69% (11/16). Subgroup with p.A775_G776insYVMA insertion in exon 20 (N=10) had median TTF of 9.6 months, ORR of 33%, and DCR of 100%.Global named used program. Heavily pretreated NSCLC with ERBB2 mutation. N=28. ORR of 19% (3/16) with DCR of 69% (11/16).

Changed Poziotinib in Solid tumours, Non-small cell lung cancer with ERBB2 A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup): 3

Comments changed: Phase 2 trial. NCT03066206. N=50. Poziotinib showed an ORR of 32% and median PFS of 5.5 months in EGFR exon 20-mutant NSCLC patients, with sensitivity influenced by insertion location (ORR: 46% near-loop vs 0% far-loop).Phase 2. ORR 43% (5/12) and DCR 83%. NCT03066206.. References changed: 3582039731588020.

Changed Poziotinib in Non-small cell lung cancer with ERBB2 A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, Exon 20 insertion, Exon 20 mutation: 3

Comments changed: Phase 2 trial. N=30. Poziotinib showed antitumor activity in patients with HER2 exon 20 mutant NSCLC with a confirmed ORR of 27%, median PFS of 5.5 months, and median OS of 15 months, despite 90% having received prior platinum-based chemotherapy.N=30. NSCLC subsequent to platinum-based chemotherapy. ORR 27%. Median DOR 5.0 months. Median PFS 5.5 months. Median OS 15 months..

Changed Margetuximab + Pembrolizumab in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification: 3

Comments changed: Phase 1b/2 CP-MGAH22-05 trial. NCT02689284. N=95. Margetuximab plus pembrolizumab showed acceptable safety and tolerability with an ORR of 18% (17/92) in patients with previously treated HER2-positive gastro-oesophageal adenocarcinoma.CP-MGAH22–05.

Changed Carboplatin + Paclitaxel + Trastuzumab in Uterine serous carcinoma with ERBB2 Amplification: 3

Comments changed: Phase 2 trial. N=61. Median PFS was significantly longer with carboplatin-paclitaxel-trastuzumab (12.6 months) versus carboplatin-paclitaxel (8.0 months) in patients with HER2-positive advanced or recurrent uterine serous carcinoma.Not TGA approved; NCCN 2A; OncoKB LOE 2.

Changed Trastuzumab + Pertuzumab in Salivary gland cancers with ERBB2 Amplification, Overexpression, L755F, D679H, G766V: 3

Comments changed: Phase 2a MyPathway trial. NCT02091141. N=19. Objective response rate (ORR) was 63% (12/19) in patients with advanced salivary gland carcinoma treated with targeted therapies matched to specific molecular alterations, including pertuzumab + trastuzumab for HER2 alterations, vismodegib for PTCH-1/SMO mutation, vemurafenib for BRAF V600 mutation, and atezolizumab for high tumor mutational burden.Phase 2A Basket. MyPathway.

Changed Ado-Trastuzumab Emtansine in Non-small cell lung cancer with ERBB2 Oncogenic mutations, V659E, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G778insCPG, G776delinsVC, exon 20 insertion: 3

Comments changed: Phase 2 trials. Trastuzumab emtansine (T-DM1) showed activity in patients with HER2-overexpressing (IHC 3+) NSCLC and HER2-mutant lung cancers, with overall response rates of 20% and 44% respectively, with responses associated with HER2 gene amplification in the HER2-overexpressing cohort.Not TGA approved. OncoKB LOE 2..

Changed Trastuzumab deruxtecan in Breast cancer with ERBB2

Alterations changed: Protein expression and NOT amplificationprotein expression and NOT amplification. Tier changed: 34. Comments changed: Phase 1b study. NCT02564900. DESTINY-Breast04. N=54. Trastuzumab deruxtecan showed an ORR of 37.0% with median DOR of 10.4 months in patients with HER2-low-expressing advanced breast cancer..

Changed Erdafitinib in Cholangiocarcinoma with FGFR2 Fusions: 3

Comments changed: Phase 2a study. LUC2001. NCT02699606. Erdafitinib showed encouraging efficacy in Asian advanced cholangiocarcinoma patients with FGFR alterations, with an ORR of 50% (60% in FGFR2-alteration positive patients) and median PFS of 5.6 months (12.4 months in FGFR2-alteration positive patients)..

Changed Rogaratinib in Urothelial carcinoma with FGFR3 High mRNA expression: 3

Comments changed: Randomised Phase 2. FORT-1. NCT03410693. In the FGFR1/3 mRNA positive population (N=87), rogaratinib demonstrated an ORR of 21% (18/87) and median OS of 8.3 months, which was not superior to chemotherapy.NCT03410693. Randomised Phase 2. FORT-1. FGFR1/3 mRNA positive population. N=87 in the Rogaratinib group. ORR was 21% (18/87), and median OS was 8.3 months. However, neither ORR or OS was superior to chemotherapy group..

Changed Sorafenib in Acute myeloid leukaemia with FLT3 Internal tandem duplication: 3

Comments changed: Phase 2 SORMAIN trial. DRKS00000591. N=83. Sorafenib maintenance therapy significantly improved RFS (HR, 0.39) and 24-month RFS probability (85.0% vs 53.3%) compared to placebo in FLT3-ITD-positive AML patients after allogeneic HCT.SORMAIN trial. Maintenance treatment. 24 months RFS 53.3% vs 85% placebo.

Changed Sorafenib in Acute myeloid leukaemia with FLT3 Internal tandem duplication: 3

Comments changed: Phase 2. N=13. Sorafenib treatment in FLT3-ITD AML patients showed initial response with clearance of bone marrow myeloblasts in 12 patients, but subsequent nonresponsiveness emerged due to expansion of LICs bearing D835 mutation..

Changed Ivosidenib + Azacitidine in Acute myeloid leukaemia with IDH1 Oncogenic mutations: 3

Comments changed: Phase Ib trial. NCT02677922. N=23. Ivosidenib plus azacitidine in newly diagnosed mIDH1 AML patients ineligible for intensive induction chemotherapy demonstrated an ORR of 78%, CR rate of 61%, 12-month OS of 82%, and was well tolerated.N=23. ORR 78%. CR 61%. OS at 12 months 82%.

Changed Imatinib in Melanoma with KIT Oncogenic mutations and NOT Amplification: 3

Comments changed: Phase 2 trial. N=25. Imatinib showed a ORR of 29% in metastatic mucosal, acral, or CSD melanoma with KIT amplifications and/or mutations, with higher response rate in KIT mutated (54%) versus KIT amplified only (0%).ORR 54% in KIT mutation.

Changed Adagrasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with KRAS G12C: 3

Comments changed: Phase 1/2 KRYSTAL-1 trial. NCT03785249. N=79. Adagrasib demonstrated an ORR of 45% and disease control rate of 96% in patients with advanced/metastatic NSCLC harboring KRAS G12C mutation, with a median time on treatment of 8.2 months.KRYSTAL-1. Combined Phase 1&2. ORR 45% (NSCLC), 17% (CRC).

Changed Adagrasib in Solid tumours, Pancreatic adenocarcinoma, Appendiceal carcinoma, Cholangiocarcinoma, Endometrial carcinoma with KRAS G12C: 3

Comments changed: Phase 1/2. KRYSTAL-1. N=57. NCT03785249. Adagrasib 600mg BD demonstrated an ORR of 35% (20/57), with 33% in PDAC subgroup and 42% in BTC. DCR was 86%. Median DOR was 5.3 months and median PFS was 7.4 months.Not TGA approved. Not FDA approved. Phase 1/2. KRYSTAL-1. N=57. NCT03785249. Adagrasib 600mg BD. ORR was 35% (20/57). DCR was 86%. Median DOR was 5.3 months. ORR was 33% in PDAC subgroup and 42% in BTC. Median PFS was 7.4 months..

Changed Savolitinib in Papillary renal cell carcinoma with MET Oncogenic mutations, Amplification: 3

Comments changed: Phase 3 SAVOIR trial. NCT03091192. N=60. Savolitinib showed numerically greater PFS (7.0 months vs 5.6 months), OS, and ORR compared to sunitinib in patients with MET-driven papillary renal cell carcinoma, with fewer grade 3 or higher AEs (42% vs 81%). Statistical significance for the primary endpoint was not demonstrated in the phase 3 SAVOIR trial due to poor recruitment.Type 1 papillary renal cell carcinoma. Note: statistical significance for the primary endpoint, PFS, was not demonstrated in the phase 3 SAVOIR trial due to poor recruitment..

Changed Entrectinib in Solid tumours with NTRK1 : 3

Alterations changed: Fusions.

Changed Larotrectinib in Solid tumours with NTRK1 : 3

Alterations changed: Fusions.

Changed Entrectinib in Solid tumours with NTRK2 : 3

Alterations changed: Fusions.

Changed Larotrectinib in Solid tumours with NTRK2 : 3

Alterations changed: Fusions.

Changed Entrectinib in Solid tumours with NTRK3 : 3

Alterations changed: Fusions.

Changed Larotrectinib in Solid tumours with NTRK3 : 3

Alterations changed: Fusions.

Changed KL590586 in Non-small cell lung cancer, Solid tumours with RET : 3

Alterations changed: Fusions.

Changed Repotrectinib with ROS1 Fusion: 3

Cancer type(s) changed: Solid tumours References changed: 10.1200/JCO.2019.37.15_suppl.9011.

Changed Repotrectinib with ROS1 Fusion, G2032R: 3

Cancer type(s) changed: Non-small cell lung cancer, Solid tumours

Changed Ceritinib in Non-small cell lung cancer with ROS1 Fusions: 3

Comments changed: Phase 2 trial. Ceritinib demonstrated clinical activity in patients with ROS1-rearranged NSCLC, with ORR of 62%, median PFS of 9.3 months, and median OS of 24 months, in patients with ROS1-rearranged NSCLC who develop resistance to crizotinib.Positive phase 2 trial..

Changed Uprosertib in Breast cancer with AKT3 Oncogenic mutations: 4

Comments changed: Preclinical study. Novel AKT inhibitors (GSK2110183 and GSK2141795) showed anti-tumor effects in mouse tumor models, with enhanced efficacy when combined with MEK inhibitor (GSK2110212; trametinib) in KRAS-driven pancreatic cancer models..

Changed Alectinib in Non-small cell lung cancer with ALK VKORC1L1-ALK fusion, T1151K: 4

Comments changed: Case report. A lung cancer patient with a novel VKORC1L1-ALK fusion and an acquired ALK T1151K mutation showed a response to alectinib, demonstrating its clinical activity against the T1151K mutation..

Changed Mivebresib in Prostate cancer with AR AR-V7, F877L, L702H: 4

Comments changed: Preclinical study. BET inhibitor ABBV-075 inhibited transcription activation downstream of AR and TMPRSS2:ETS fusion proteins, showing antiproliferative activity in models with resistance to second-generation antiandrogens and AR splice variant AR-V7 and gain-of-function mutations, F877L and L702H.Preclinical evidence only.

Changed Therapy in Glioma with AR Protein expression: 4

Therapy changed: EnzalutamideCYP17A1 inhibitor. Comments changed: Preclinical study. Androgen receptor (AR) was amplified in 27% of glioblastoma specimens from men and 38.2% from women, with overexpression of AR-RNA and AR-protein in 93% and 56% of samples, respectively; AR antagonists induced concentration-dependent death in glioblastoma cell lines, and enzalutamide reduced tumor volume by 72% in human glioma xenografts.Weak evidence.

Changed Capivasertib in Gastric cancer with ARID1A : 4

Alterations changed: Oncogenic mutations.

Changed Tuvusertib in Solid tumours with ARID1A : 4

Alterations changed: Oncogenic mutations.

Changed Ceralasertib in Chronic lymphocytic leukaemia with ATM : 4

Alterations changed: Oncogenic mutations.

Changed Ceralasertib + Chlorambucil, Ceralasertib + Fludarabine, Ceralasertib + Bendamustine, Ceralasertib + Ibrutinib in Chronic lymphocytic leukaemia with ATM : 4

Alterations changed: Oncogenic mutations.

Changed VE-821 + Cisplatin in Solid tumour with ATM : 4

Alterations changed: Oncogenic mutations.

Changed Tuvusertib in Solid tumours with ATRX : 4

Alterations changed: Oncogenic mutations.

Changed Therapy in Solid tumours with BRAF Fusions: 4

Therapy changed: FORE8394, RAF dimer inhibitorPLX8394, RAF dimer inhibitor.

Changed LY3009120 in Solid tumours with BRAF L485_P490del: 4

Comments changed: Class II BRAF mutations. Preclinical study. Oncogenic BRAF in-frame deletion in the alpha-C helix identified in various cancers were found to be sensitive to RAF dimer inhibitor LY3009120, which showed tumor growth regression in tumor models, whereas vemurafenib was inactive.Class II mutations. BRAF in-frame deletion in the alpha-C helix favour dimerization and is sensitive to LY3009120 but resistant to Vemurafenib.

Changed Sorafenib in Solid tumours with BRAF L485_P490delinsF, L485_P490delinsY: 4

Comments changed: Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivity with RAF inhibitors.Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors..

Changed Trametinib in Melanoma with BRAF L597, L597Q: 4

Comments changed: Retrospective analysis of 5 patients with non-V600 BRAF mutation (K601E and L597Q) metastatic melanoma showed 3 patients achieved partial response to trametinib, with manageable toxicity and reduced phospho-ERK signalling in paired biopsies.Single case report.

Changed Therapy in Solid tumours with BRAF L597, L597Q, K601, K601E: 4

Therapy changed: FORE8394PLX8394.

Changed Dabrafenib + Trametinib in Melanoma with BRAF T599_V600insT: 4

Comments changed: Case reports. BRAF T599dup-mutated melanoma patients showed response to BRAF and MEK inhibitors.Case series..

Changed Vemurafenib + Cobimetinib in Pancreatic adenocarcinoma with BRAF T599_V600insT: 4

Comments changed: Retrospective case series of 81 patients with RAF family-mutated pancreatic cancer showed varied responses to targeted and standard therapies across different RAF mutational subgroups: BRAF V600/Exon 15, BRAF or RAF1 fusions, and Exon 11 mutations. One case with T599 duplication had 20 weeks duration of therapy.Case report. Duration of therapy was 20 week.

Changed Therapy in Solid tumours with BRAF V600E: 4

Therapy changed: FORE8394PLX8394. Comments changed: Preclinical study. RAF inhibitor FORE8394 disrupts BRAF dimers and selectively inhibits ERK signaling in tumors driven by dimeric BRAF mutants and BRAF V600 monomers.Preclinical study. RAF inhibitor PLX8394 disrupts BRAF dimers and selectively inhibits ERK signaling in tumors driven by dimeric BRAF mutants and BRAF V600 monomers..

Changed Abemaciclib, Palbociclib in Non-small cell lung cancer with CDKN2A Loss of protein expression: 4

Comments changed: Phase 2 clinical trial and preclinical study. Palbociclib showed stable disease in 50% of p16-null NSCLC patients with median OS of 16.6 months, and preclinical data showed synergy with mTOR inhibition, particularly in tumors carrying RAS mutations.Cytostatic.

Changed Osimertinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

Comments changed: Case reports. Two NSCLC patients with EGFR kinase domain duplication (KDD) mutation, one of whom achieved stable disease with osimertinib after resistance to afatinib, highlighting osimertinib as a potential effective therapy following resistance to first- and second-generation EGFR-TKIs..

Changed Afatinib in Non-small cell lung cancer with EGFR L747P, L747S: 4

Comments changed: Preclinical and clinical study. Afatinib showed improved PFS (11.97 months) and ORR (80%) in patients with lung adenocarcinoma harboring uncommon EGFR p.L747P and p.L747S mutations, with no patients acquiring p.T790M resistance after afatinib failure.Retrospective sample.

Changed Afatinib, Osimertinib in Non-small cell lung cancer with EGFR L747S, D761Y, T854A: 4

Comments changed: Preclinical study. Irreversible EGFR-TKIs showed efficacy against uncommon secondary resistant EGFR mutations L747S, D761Y, and T854A.Cell line study.

Changed Gefitinib in Non-small cell lung cancer with EGFR : 4

Alterations changed: L833V, H835L. Comments changed: Case report. A lung adenocarcinoma patient with a heterozygous complex mutation of L833V and H835L in the EGFR gene showed a good response to gefitinib treatment..

Changed Afatinib, Osimertinib in Non-small cell lung cancer with EGFR T751_I759delinsS: 4

Comments changed: Case report. Lung adenocarcinoma patient with rare EGFR T751_I759delinsS mutation showed initial good response to afatinib and subsequent response to osimertinib after developing resistance to afatinib, highlighting potential treatment options for patients with rare EGFR mutations..

Changed Erlotinib + Osimertinib in Non-small cell lung cancer with EGFR T790M and C797S and T790M-C797S trans-allelic conformation: 4

Comments changed: Case report. Lung adenocarcinoma with EGFR 19Del/T790M/in trans-C797S mutations demonstrated durable clinical response to combined first- and third-generation EGFR tyrosine kinase inhibitor therapy..

Changed AMG-596 in Glioma, Glioblastoma with EGFR vIII: 4

Comments changed: Preclinical study. EGFRvIII-targeted bispecific T-cell engager shows therapeutic activity in glioblastoma by redirecting T cells to eliminate EGFRvIII-expressing GBM cells..

Changed Erlotinib, Lapatinib in Glioblastoma with EGFR vIII, EGFR-SEPT14 fusion: 4

Comments changed: Preclinical study. Integrated analysis of genomic alterations in glioblastoma revealed LZTR1 mutations with loss of heterozygosity, CTNND2 loss-of-function mutations associated with mesenchymal phenotype, and EGFR fusions (e.g., EGFR-SEPT14) that activate STAT3 signaling and confer sensitivity to EGFR inhibition.Xenograft model..

Changed Dabrafenib + Trametinib + Osimertinib in Non-small cell lung cancer with EGFR+BRAF EGFR:Oncogenic mutations and BRAF:V600E: 4

Comments changed: Case report. A patient with EGFR-mutant/BRAF V600E lung adenocarcinoma showed impressive radiological and ctDNA response to combination therapy with dabrafenib, trametinib, and osimertinib, suggesting potential efficacy in patients with acquired BRAF V600E resistance mutation..

Changed MK-2206 + Gemcitabine in Solid tumours with EGFR+ERRFI1 EGFR:low expression AND ERRFI1:Oncogenic mutations: 4

Comments changed: Cell line study. ERRFI1 differentially regulates EGFR and AKT pathways in a context-dependent manner, promoting cell growth and chemotherapy desensitization in EGFR-low cells while inhibiting growth in EGFR-high cells. AKT inhibitors sensitize cells to chemotherapy.Cell line study of effect of EFFRI1. AKT inhibitor sensitises cell to chemotherapy.

Changed Therapy in Non-small cell lung cancer with EGFR+MET EGFR:Oncogenic mutations and MET:amplification and NOT EGFR:T790M: 4

Therapy changed: Gefitinib + CapmatinibGefitinib + Savolitinib. Comments changed: Phase Ib/II study. Capmatinib plus gefitinib showed clinical activity in patients with EGFR-mutated, MET-dysregulated NSCLC who progressed on EGFR-TKI, particularly in those with high MET-amplified tumors (ORR 47% with MET gene copy number ≥ 6), addressing a predominant EGFR-TKI resistance mechanism..

Changed Osimertinib + Crizotinib in Non-small cell lung cancer with EGFR+MET EGFR:T790M and MET:amplification: 4

Comments changed: Case report. MET amplification emerged as a resistance mechanism after T790M positivity in EGFR-mutant NSCLC, and was effectively targeted with a combination of crizotinib and osimertinib, showing tolerability and efficacy.Case reports. References changed: 28274743, 30881166, 31157314.

Changed Osimertinib + Pralsetinib in Non-small cell lung cancer with EGFR+RET EGFR:Oncogenic mutations and RET:fusion: 4

Comments changed: Preclinical study and case reports. RET fusions, such as CCDC6-RET, were identified as a mechanism of acquired resistance to osimertinib in EGFR-mutant NSCLC, and combined EGFR and RET inhibition with osimertinib and BLU-667 showed effectiveness in treating patients with RET-mediated resistance.Two case reports.

Changed Osimertinib + Crizotinib in Non-small cell lung cancer with EGFR+ROS1 EGFR:Oncogenic mutations and ROS1:fusion: 4

Comments changed: Preclinical study. GOPC-ROS1 rearrangement identified as an acquired resistance mechanism to osimertinib, with observed response to crizotinib combined treatments in lung adenocarcinoma.Case report.

Changed Lapatinib + Trastuzumab in Breast cancer with ERBB2 D769Y, R896C: 4

Comments changed: Preclinical study. Activating HER2 mutations identified in 25 breast cancer patients lacking HER2 gene amplification were functionally characterized, showing sensitivity to neratinib, an irreversible HER2 inhibitor, but variable response to lapatinib..

Changed Afatinib in Non-small cell lung cancer with ERBB2 Exon 16 skipping mutation: 4

Comments changed: Preclinical study. HER2 ex16 deletion, a novel HER2 splice variant, was identified as a potential osimertinib resistance mechanism in EGFR L858R/T790M-positive NSCLC, and its resistance was synergistically reversed by combining osimertinib with afatinib..

Changed Neratinib in Breast cancer with ERBB2 G309A, V777L, D769H, V842I, L755S, L755_759del: 4

Comments changed: Preclinical study. HER2 somatic mutations identified in 25 breast cancer patients without HER2 gene amplification, with 7 activating mutations sensitive to neratinib, suggesting potential benefit of HER2-targeted therapy..

Changed Trastuzumab, Ado-Trastuzumab Emtansine in Gastric cancer with ERBB2 MDK-ERBB2 fusion, Fusions: 4

Comments changed: Biomarker analysis. Whole-transcriptome sequencing identified 3 novel HER2 fusions (ZNF207-HER2, MDK-HER2, and NOS2-HER2) in 14% of 21 HER2-amplified gastric cancer samples. Trastuzumab showed activity in MDK-HER2 but not ZNF207-HER2 expressing xenografts due to differential binding..

Changed Afatinib in Lung adenocarcinoma with ERBB2 Oncogenic mutations: 4

Comments changed: Phase 2 study. In Cohort 3, one unconfirmed response from seven patients (5 SD). Note individual and concomitant mutations not reported.One unconfirmed response from seven patients (5 SD). Individual and concomitant mutations not reported..

Changed Margetuximab in Solid tumours with ERBB2 Overexpression: 4

Comments changed: Phase 1 study. NCT01148849. N=66. Margetuximab showed single-agent activity in patients with HER2-positive advanced solid tumors, with 12% (7/60) confirmed partial responses and 50% (30/60) stable disease, including durable responses in breast cancer patients..

Changed GQ1001 in Solid tumour with ERBB2 Overexpression, Amplification: 4

Comments changed: Preclinical study. GQ1001, a next-generation HER2-targeting ADC, demonstrated robust anti-tumor activity in HER2-positive models, including those resistant to anti-HER2 TKIs and/or mAbs, with enhanced linker stability and reduced off-target toxicity..

Changed Afatinib, Neratinib, Poziotinib in Acute myeloid leukaemia with ERBB2 : 4

Alterations changed: R188C, P489L, L1157R. Comments changed: Preclinical study. ERBB2 mutations (R188C, P489L, and L1157R) identified in leukaemia patients are oncogenic and sensitive to irreversible pan-HER inhibitors, such as afatinib, neratinib, and poziotinib, with nanomolar IC50 values, and to trastuzumab, particularly for extracellular domain mutants. Updated: 2025-05-28.

Changed Lapatinib + Capecitabine in Extramammary Paget’s disease with ERBB2 S310F: 4

Comments changed: Case report. A patient with metastatic extramammary Paget's disease associated with adnexal adenocarcinoma harbouring ERBB2 S310F mutation responded to anti-HER2 drugs..

Changed Trastuzumab + Carboplatin in Extramammary Paget’s disease with ERBB2 S310F: 4

Comments changed: Case report. A patient with ERBB2(S310F) mutated metastatic extramammary Paget's disease initially responded to trastuzumab and carboplatin, but developed resistance with additional genomic alterations including ERBB3(A232V) and PIK3CA(G106V) mutations and MET and CDK6 amplification..

Changed Pyrotinib in Breast cancer with ERBB2 : 4

Alterations changed: S310F, S310Y, L403V, L755S, D769Y, A775_Y776insYVMA (Y772_A775dup), V777L, T862AS310F, S310Y, L403V, L755S, D769Y, A775_Y776insYVMA, V777L, T862A. Comments changed: Phase 2 trial. NCT03412383. Pyrotinib monotherapy achieved an ORR of 40% and CBR of 60% in HER2 amplification-negative, mutation-positive metastatic breast cancer patients, with a median PFS of 4.9 months. Responses or prolonged SD were seen in S310F, L755S, D769Y, V777L, T862A, and A775_Y776insYVMA (Y772_A775dup)..

Changed Lapatinib, Afatinib in Urothelial carcinoma with ERBB2 S310F, S653C, D277H and S310F: 4

Comments changed: Preclinical study. ERBB2 mutations were found in 15% of urothelial bladder cancer cell lines, and these mutations enhanced ErbB2 activation and predicted a response to lapatinib, with 93% reversal of mutant-induced growth patterns..

Changed Trastuzumab, Pertuzumab, Afatinib, Neratinib, Lapatinib in Solid tumours with ERBB2 V659E, G660D, G660R, R678Q, V697L, Q709, Transmembrane domain mutation, Juxtamembrane domain mutation: 4

Comments changed: Preclinical study. Activating HER2 transmembrane and juxtamembrane domain mutations (G660D, R678Q, E693K, Q709L) identified in patient tumors were found to be sensitive to anti-HER2 antibodies and small-molecule kinase inhibitors, with a germline G660D mutant lung cancer patient showing clinical response to HER2 blockade..

Changed H3Mab-17 in Colorectal adenocarcinoma with ERBB3 Overexpression: 4

Comments changed: Preclinical study. Anti-HER3 monoclonal antibody H(3)Mab-17 showed antitumor activity, inducing ADCC and CDC against Caco-2 cells and significantly reducing tumor growth in a Caco-2 xenograft model..

Changed Palbociclib in Breast cancer with ESR1 Fusion, ESR1-YAP1 fusion, ESR1-PCDH11X fusion: 4

Comments changed: Preclinical study. ESR1 gene fusions in ER-positive breast cancer confer estrogen-independent growth, anti-estrogen resistance, and metastatic progression, but remain sensitive to CDK4/6 inhibitors..

Changed AZD9496 in Breast cancer with ESR1 Protein expression: 4

Comments changed: Phase 1 trial. AZD9496, an oral selective estrogen receptor degrader, showed evidence of prolonged disease stabilization in heavily pretreated ER(+)/HER2(-) advanced breast cancer patients, with a partial response in one patient and stable disease at 12 months in four patients..

Changed Cisplatin in Solid tumours with FANCA S1088F: 4

Comments changed: Preclinical study. Germline FANCA S1088F mutation disrupts FANC protein complex, resulting in increased sensitivity to DNA damaging agents, suggesting potential predictive biomarker for prostate cancer treatment response.Case report.

Changed Therapy in Head and neck squamous cell carcinoma with FANCC Loss of protein expression: 4

Therapy changed: OlaparibPARP inhibitor. Comments changed: Preclinical study. Fanconi anemia head and neck cancers acquired relative interstrand crosslinker resistance and PARP inhibitor sensitivity, with increased PARP-mediated DNA damage sensing and repair in Fanconi anemia-deficient cells.Preclinical data only.

Changed Therapy in Pancreatic adenocarcinoma with FANCG Oncogenic mutations: 4

Therapy changed: ATM inhibitor, KU-55933. Comments changed: Preclinical study. FA pathway-deficient tumor cells are sensitive to ATM inhibition, suggesting a potential therapeutic strategy for tumors with FA pathway dysfunction, particularly in cancers with FA pathway deficiency such as certain breast, ovarian, pancreatic, and hematological tumors.Preclinical data only.

Changed PRN1371 in Hepatocellular carcinoma with FGF19 Amplification: 4

Comments changed: FGF19-FGFR4 signaling pathway is a potential target for HCC treatment, with various FGFR4/pan-FGFR inhibitors in different clinical trial phases, offering future perspectives for improving efficacy in relation to aberrant FGF19-FGFR4 expression.Cell line study.

Changed Erdafitinib in Solid tumours with FGFR1 Amplification, Fusion, Oncogenic mutations and NOT V561: 4

Comments changed: Phase 1 study. NCT01703481. Erdafitinib showed clinical activity in advanced solid tumors with FGFR mutations or fusions, particularly in urothelial carcinoma (ORR 46.2%) and cholangiocarcinoma (ORR 27.3%), with median response durations of 5.6 and 11.4 months, respectively.NCT01703481, ORR 46.2%.

Changed AZD4547 in Solid tumours with FGFR1 : 4

Alterations changed: FusionsAmplification, Fusion, Oncogenic mutations. Comments changed: Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions.No response in these cohorts. References changed: 32463741, 10.1200/JCO.2018.36.15_suppl.2503, 10.1200/jco.2014.32.15_suppl.803510.1200/JCO.2018.36.15_suppl.2503, 10.1200/jco.2014.32.15_suppl.8035, 32463741.

Changed Erdafitinib in Non-small cell lung cancer with FGFR2 FGFR2-BICC1 fusion: 4

Comments changed: Case report showing partial response to erdafitinib. Updated: 2022-02-16. References changed: 35050756, 10.1200/PO.20.00110.

Changed Lirafugratinib in Cholangiocarcinoma with FGFR2 FGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M: 4

Comments changed: Preclinical study. RLY-4008, a highly selective FGFR2 inhibitor, showed activity across various FGFR2 alterations and resistance mutations, inducing regression in xenograft models with FGFR2 resistance mutations while sparing FGFR1 and FGFR4, suggesting broad therapeutic potential in FGFR2-driven cancers..

Changed AZD4547 in Solid tumours with FGFR3 Fusions: 4

Comments changed: Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions.Response in small numbers (2/9). References changed: 10.1200/JCO.2018.36.15_suppl.2503, 32463741.

Changed TYRA-300 in Solid tumours with FGFR3 Fusions, FGFR3-TACC3 fusion, V555M, V555L, V555G, V555K, K650M, K650E, Oncogenic mutations, S249C, R248C, Y373C, G370C: 4

Comments changed: Preclinical study. TYRA-300 is a potent FGFR3-selective inhibitor targeting FGFR3 alterations in urothelial cancers and achondroplasia. It was designed to be effective against activating FGFR3 mutations and gatekeeper resistance mutations (V555L/M). Preclinical studies demonstrate significant FGFR3 isoform selectivity, potentially limiting toxicities observed with pan-FGFR inhibitors.. References changed: 10.1016/j.annonc.2022.07.591, 32463741.

Changed Ponatinib, Dovitinib in Cholangiocarcinoma with FGFR3 N540K, V555M, L608V: 4

Comments changed: Preclinical study and case series. Polyclonal secondary FGFR2 mutations in the kinase domain were identified in cfDNA and biopsies of FGFR2 fusion-positive cholangiocarcinoma patients, driving acquired resistance to FGFR inhibitor BGJ398, and were surmountable by distinct FGFR inhibitors..

Changed Trametinib in Non-small cell lung cancer with GNAS R201C, R201H: 4

Comments changed: Case report. A NSCLC patient with osimertinib resistance harboring GNAS R201C and R201H mutations showed stable disease when treated with trametinib..

Changed Trametinib in Appendiceal cancer with GNAS R201H: 4

Comments changed: Case report. A patient with appendiceal adenocarcinoma and a GNAS R201H mutation experienced clinical benefit from trametinib, with a decrease in tumor markers and improvement in quality of life..

Changed BGB-B2033 in Hepatocellular carcinoma with GPC3 Protein expression: 4

Comments changed: Preclinical study. BGB-B2033, a 4-1BB/GPC3 bispecific antibody, exhibits potent antitumor activity in GPC3-expressing tumor models.. References changed: 10.1158/1538-7445.AM2025-6009NCT06427941.

Changed MT-303 in Hepatocellular carcinoma with GPC3 Protein expression: 4

Comments changed: Preclinical study. MT-303, an LNP-formulated GPC3-specific CAR mRNA, demonstrated improved expression and anti-tumor activity in a hepatocellular carcinoma xenograft model (HepG2). 10.1136/jitc-2024-SITC2024.1125. References changed: 10.1136/jitc-2024-SITC2024.1125NCT06478693.

Changed Cisplatin in Breast cancer with Homologous Recombination Deficiency Score High: 4

Comments changed: Preclinical and clinical study. Homologous recombination deficiency (HRD) score, defined as HRD score ≥42 or BRCA1/2 mutation, predicts response to platinum-containing neoadjuvant chemotherapy in triple-negative breast cancer patients, including those with BRCA1/2 nonmutated tumors with high HRD scores..

Changed HB-201, HB-201 + HB-202 in HPV16-positive cancers with HPV genotype HPV16-positive: 4

Comments changed: Phase 1/2 study. NCT04180215. HB-201 monotherapy demonstrated preliminary antitumor activity in 16 HPV16+ cancer patients (predominantly HNSCC) with 2 partial responses and 6 stable disease outcomes. Alternating HB-201 and HB-202 therapy achieved stable disease in 2 of 2 patients..

Changed Selumetinib, Cobimetinib, PD0325901 in Solid tumours with HRAS Oncogenic mutations: 4

Comments changed: Preclinical study. Mutant HRAS cancer cell lines showed sensitivity to MEK inhibitors (AZD6244, MEK162, and PD0325901) and mTOR inhibition, with synergistic effects observed with combined MEK and mTOR inhibition, suggesting a potential therapeutic target for HRAS mutant tumors.Cell line study.

Changed Olutasidenib in Glioma with IDH1 R132: 4

Comments changed: Phase Ib/II trial. Olutasidenib demonstrated preliminary clinical activity in patients with relapsed/refractory IDH1-mutant glioma, with 8% achieving partial response and 32% having stable disease, in those harbouring IDH1 R132 mutations.. References changed: 35639513, 10.1200/JCO.2020.38.15_suppl.2505.

Changed Therapy in Gastrointestinal stromal tumour with KIT Exon 11 mutation, Exon 11 deletion, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829P: 4

Therapy changed: BezuclastinibPLX9486.

Changed Sorafenib in Gastrointestinal stromal tumour with KIT V560D, A502_Y503dup, V654A, T670I, D820A, D820E, D820G, D820Y, N822H, N822K, Y823D, A829P: 4

Comments changed: Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842..

Changed Therapy in Melanoma with MAP2K2 Q60P

Therapy changed: Dabrafenib + Trametinib + Omipalisib. Tier changed: 4R2. Comments changed: Preclinical study. Concurrent MEK2-Q60P mutation and BRAF amplification/V600E were identified in melanoma cells resistant to BRAF and MEK inhibitors, conferring sustained MAPK activation and on-target resistance, which was addressed by a triple combination of dabrafenib, trametinib, and GSK2126458..

Changed Anetumab Ravtansine with MSLN Protein expression, Overexpression: 4

Cancer type(s) changed: Solid tumours, Mesothelioma, Ovarian cancer Comments changed: Phase 1 study. Anetumab ravtansine showed clinical activity in patients with high mesothelin expression, with 1 complete response and 11 partial responses among 148 patients with various solid tumors, including mesothelioma and ovarian cancer..

Changed Everolimus in Urothelial carcinoma with MTOR E2014K, E2419K: 4

Comments changed: Phase 2 study. Everolimus showed biological activity in a subset of patients with advanced urothelial carcinoma, with 2 partial responses and 12 minor regressions, suggesting a potential role for mTOR pathway inhibition, although no clear association was observed between mTOR pathway marker expression and response..

Changed Temsirolimus in Renal cell carcinoma with MTOR L1460P, L2209V, L2427Q: 4

Comments changed: Retrospective observational study. Mutations in MTOR, TSC1, or TSC2 were associated with response to rapalogs in metastatic renal cell carcinoma patients, with higher frequency of mutations in responders (28%) compared to nonresponders (11%).OncoKB LOE 3; Retrospective association only.

Changed Temsirolimus in Breast cancer with MTOR Oncogenic mutations: 4

Comments changed: Phase 2 study. Temsirolimus showed antitumor activity with an ORR of 9.2% in heavily pretreated patients with locally advanced or metastatic breast cancer, with similar efficacy observed at both 75mg and 250mg doses..

Changed Everolimus in Renal cell carcinoma with MTOR Q2223K: 4

Comments changed: Retrospective observational study. Mutations in MTOR, TSC1, or TSC2 were associated with response to rapalogs in metastatic renal cell carcinoma patients, with higher frequency of mutations in responders (28%) compared to nonresponders (11%).OncoKB LOE 3; Retrospective association only.

Changed Sapanisertib + Metformin in Solid tumours with MTORC1 Oncogenic mutations: 4

Comments changed: Phase 1 trial. NCT03017833. N=30. Sapanisertib + metformin showed anti-tumor activity in patients with mTOR/AKT/PI3K pathway alterations, including 4 patients achieving partial response, 3 of whom had PTEN mutations and 1 had AKT and mTOR mutation..

Changed CX-5461 in Neuroblastoma with MYC Amplification, Overexpression: 4

Comments changed: Preclinical study. CX-5461 down-regulates MYCN protein and suppresses neuroblastoma tumor growth, particularly in MYCN-amplified tumors. Xenograft models using the KELLY cell line demonstrate orthotopic tumor growth suppression following CX-5461-induced MYCN downregulation.Xenograft model established on KELLY cell line CX-5461 leads to MYCN downregulation and suppress orthotopic tumour growth..

Changed CX-5461 in Small-cell lung cancer with MYCL Overexpression: 4

Comments changed: Preclinical study. MYCL amplification in SCLC promotes tumor-forming capacity and ribosomal biogenesis, and deletion of Mycl suppresses SCLC, suggesting RNA Pol I inhibition as a potential therapeutic target, which showed significant tumor inhibition in an autochthonous Rb/p53-deleted mouse SCLC model..

Changed Enfortumab Vedotin in Solid tumours with NECTIN4 Protein expression: 4

Comments changed: Phase 1 EV-101 study. Enfortumab vedotin showed antitumor activity in Nectin-4-positive metastatic urothelial carcinoma patients, with an ORR of 43% and median OS of 12.3 months, indicating sensitivity to the drug in heavily pretreated patients..

Changed Trametinib in Glioblastoma with NF1 Oncogenic mutations (germline): 4

Comments changed: Case report. A 24-year-old male with neurofibromatosis type I-associated glioblastoma showed clinical and radiological benefit from the MEK inhibitor, trametinib..

Changed RMC-4550 in Solid tumours with NF1 Oncogenic mutations, Loss-of-function mutations, N184fs, Q1336*: 4

Comments changed: Preclinical study. SHP2 phosphatase inhibitor RMC-4550 was effective in human cancer models with RAS-GTP-dependent oncogenic BRAF (class 3 BRAF mutants), NF1 loss, or nucleotide-cycling oncogenic RAS (KRAS(G12C)), by disrupting SOS1-mediated RAS-GTP loading and decreasing oncogenic RAS/RAF/MEK/ERK signalling.Cell line study..

Changed Mirdametinib + JQ1 in Malignant peripheral nerve sheath tumor with NF1+SUZ12 NF1:Loss-of-function mutations AND SUZ12:Loss-of-function mutations: 4

Comments changed: Preclinical study. Loss of PRC2 component SUZ12 sensitizes cancers with NF1 mutations to BRD4-based therapies by amplifying Ras-driven transcription..

Changed Everolimus + Docetaxel in Urothelial carcinoma with NF2 Loss-of-function mutations: 4

Comments changed: Case report. Exceptional response observed in urothelial carcinoma bearing an NF2 mutation when treated with everolimus in combination with taxane..

Changed VT104 in Mesothelioma with NF2 Oncogenic mutation, Deletion: 4

Comments changed: Preclinical study. Small molecule inhibitors of TEAD auto-palmitoylation selectively inhibit proliferation and tumor growth of NF2-deficient mesothelioma, providing a potential therapeutic strategy for targeting the Hippo-YAP pathway in YAP-driven cancers..

Changed SCH772984 in Solid tumours with NRAS Oncogenic mutations: 4

Comments changed: Preclinical study. SCH772984, a novel ERK1/2 inhibitor, showed activity in models with BRAF, NRAS, or KRAS mutations and effectively inhibited MAPK signaling in BRAF or MEK inhibitor-resistant models..

Changed Zenocutuzumab in Solid tumours with NRG1 Fusion: 4

Comments changed: Case series and preclinical study. MCLA-128, a bispecific HER2/3 antibody, showed clinical responses in patients with NRG1 fusion-positive cancers, including pancreatic ductal adenocarcinoma and non-small cell lung cancer, by inhibiting ligand-driven activation of the HER3 pathway..

Changed Zenocutuzumab in Solid tumours with NRG1 Fusion, CD74-NRG1 fusion, CLU-NRG1 fusion, ATP1B1-NRG1 fusion, SLC3A2-NRG1 fusion, APP-NRG1 fusion: 4

Comments changed: Preclinical and case series study. Zenocutuzumab, a HER2xHER3 bispecific antibody, showed effectiveness in NRG1 fusion-positive cancer models and patients. In a cohort of 3 patients with NRG1 fusion-positive metastatic cancer, 2 achieved rapid and durable responses: 2 pancreatic cancer patients with ATP1B1-NRG1 fusion and 1 non-small cell lung cancer patient with CD74-NRG1 fusion.N=3. 2/3 patients with NRG1 fusion-positive metastatic cancer achieved rapid responses, including 2 with ATP1B1-NRG1 pancreatic cancer and 1 with CD74-NRG1 non-small cell lung cancer..

Changed Seribantumab in Breast cancer, Non-small cell lung cancer, Ovarian cancer, Solid tumours with NRG1 Fusion, DOC4-NRG1 fusion, SLC3A2-NRG1 fusion, CD74-NRG1 fusion: 4

Comments changed: Preclinical study. Seribantumab effectively inhibits growth of patient-derived and isogenic cell line and xenograft models with oncogenic NRG1 fusions in breast, lung, and ovarian cancers, inducing tumor regression by blocking activation of ERBB family members and downstream signaling.Seribantumab inhibits in vitro and in vivo of NRG1 fusion in breast, lung, and ovarian patient-derived cancer models..

Changed Lumretuzumab + Erlotinib in Non-small cell lung cancer with NRG1 Fusion; SLC3A2-NRG1 fusion: 4

Comments changed: Case reports. Two patients with invasive mucinous lung adenocarcinoma harboring NRG1 fusion achieved at least 16 weeks of progression-free survival when treated with lumretuzumab, an anti-HER3 antibody, in combination with erlotinib.Case report of invasive mucinous adenocarcinoma of lung. NRG fusion.

Changed Afatinib in Non-small cell lung cancer with NRG1 Fusions: 4

Comments changed: Registry study. NRG1 fusion-positive lung cancers showed varied clinicopathologic features and responded poorly to chemotherapy (ORR 13-14%) and immunotherapy (ORR 0-20%), but afatinib achieved an ORR of 25% regardless of fusion type. CD74-NRG1 and non-CD74-NRG1 have similar ORR (22% and 27% respectively).Retrospective registry-based study. Afatinib ORR 25%. CD74-NRG1 and non-CD74-NRG1 have similar ORR (22% and 27% respectively)..

Changed Afatinib in Pancreatic adenocarcinoma with NRG1 Fusions, ATP1B1-NRG1 fusion: 4

Comments changed: Preclinical study and case series. NRG1 gene fusions were identified in KRAS wild-type pancreatic ductal adenocarcinoma. Two patients with NRG1 fusion-positive tumors treated with afatinib demonstrated significant and rapid response..

Changed Zenocutuzumab in Breast cancer with NRG1 SLC3A2-NRG1 fusion: 4

Comments changed: Case report. Sustained tumor regression observed with Zenocutuzumab, a bispecific antibody targeting HER2/HER3 signaling, in NRG1 fusion-positive, estrogen receptor-positive breast cancer..

Changed Larotrectinib in Oesophageal squamous cell carcinoma with NTRK1 Amplification: 4

Comments changed: Case report. A patient with metastatic esophageal carcinoma harboring NTRK1 gene amplification showed significant tumor shrinkage and decrease in tumor markers after treatment with larotrectinib, suggesting potential efficacy of larotrectinib in cases with NTRK gene amplification.Single case report showing partial response to larotrectinib with DOR 3.7 month..

Changed ICP-723 in Solid tumours with NTRK1 Fusion: 4

Comments changed: Phase 1/2 trial. NCT04685226. ICP-723, a next-generation pan-TRK inhibitor, showed encouraging efficacy in patients with NTRK gene fusion positive tumors with an ORR of 66.7% (4 PR) and DCR of 100%, including intracranial activity in a patient with brain metastasis, and demonstrated activity against various tumor types.Phase 1. NCT04685226. Four of 6 responders with NTRK fusion.

Changed Taletrectinib in Solid tumours with NTRK1 Fusion: 4

Comments changed: Preclinical study. DS-6051b induces growth inhibition in NTRK-rearranged cancers in vitro and in vivo..

Changed ICP-723 in Solid tumours with NTRK2 Fusion: 4

Comments changed: Phase 1/2 trial. NCT04685226. ICP-723, a next-generation pan-TRK inhibitor, showed encouraging efficacy in patients with NTRK gene fusion positive tumors with an ORR of 66.7% (4 PR) and DCR of 100%, including intracranial activity in a patient with brain metastasis, and demonstrated activity against various tumor types.Phase 1. NCT04685226. Four of 6 responders with NTRK fusion.

Changed Taletrectinib in Solid tumours with NTRK2 Fusion: 4

Comments changed: Preclinical study. DS-6051b induces growth inhibition in NTRK-rearranged cancers in vitro and in vivo..

Changed Larotrectinib in Ependymoma with NTRK2 KANK1-NTRK2 fusion: 4

Comments changed: Case report. Recurrent disseminated ependymoma harboring a KANK1-NTRK2 fusion experienced a durable response to larotrectinib, a TRK inhibitor, with significant clinical and radiographic improvement, highlighting the importance of integrated genomic profiling in pediatric CNS tumors with NTRK fusions.. References changed: 3465109510.1200/PO.20.00375.

Changed ICP-723 in Solid tumours with NTRK3 Fusion: 4

Comments changed: Phase 1/2 trial. NCT04685226. ICP-723, a next-generation pan-TRK inhibitor, showed encouraging efficacy in patients with NTRK gene fusion positive tumors with an ORR of 66.7% (4 PR) and DCR of 100%, including intracranial activity in a patient with brain metastasis, and demonstrated activity against various tumor types.Phase 1. NCT04685226. Four of 6 responders with NTRK fusion.

Changed Taletrectinib in Solid tumours with NTRK3 Fusion: 4

Comments changed: Preclinical study. DS-6051b induces growth inhibition in NTRK-rearranged cancers in vitro and in vivo..

Changed Therapy in Pancreatic adenocarcinoma with PALB2 Loss-of-function mutations: 4

Therapy changed: Cisplatin + Gemcitabine, Cisplatin + Gemcitabine + VeliparibPARP inhibitor. Comments changed: Phase 2 trial. Significant responses observed in patients with pancreas adenocarcinoma and germline BRCA/PALB2 mutation, with Response Rate (RR) of 74.1% and 65.2% in patients treated with cisplatin and gemcitabine with or without veliparib, respectively.. References changed: 28242752, 31976786, 31806540, NCT01682772.

Changed Therapy in Prostate cancer with PALB2 Oncogenic mutations: 4

Therapy changed: RucaparibPARP inhibitor. Comments changed: Phase 2 TRITON2 trial. NCT02952534. Responses to Rucaparib observed in patients with PALB2 alterations, among other DDR-associated genes, but limited responses seen in patients with ATM, CDK12, or CHEK2 alterations..

Changed Talazoparib in Prostate cancer with PALB2 Oncogenic mutations: 4

Comments changed: Phase 2 TALAPRO-1 trial. NCT03148795. Talazoparib demonstrated antitumour activity in metastatic castration-resistant prostate cancer with DDR-HRR gene alterations, achieving an objective response rate of 29.8% (31/104) in patients with measurable soft-tissue disease. In the PALB2 subgroup (N=4), 1 confirmed partial response was observed.TALAPRO-1. Phase 2. N=4. 1 PR..

Changed FOLFIRINOX in Pancreatic adenocarcinoma with PALB2 Oncogenic mutations (germline): 4

Comments changed: Retrospective observational study. Patients with PALB2 mutation (n=4), along with BRCA1 and BRCA2 mutants, had a high ORR (58%) and prolonged rwPFS (10.1 months) when treated with platinum-based chemotherapy.Retrospective cohort study. Only 4 patients..

Changed Olaparib, Rucaparib, Talazoparib in Solid tumours with PBRM1 Loss-of-function mutations, Loss of protein expression: 4

Comments changed: Preclinical study. PBRM1 deficiency is synthetic lethal with DNA repair inhibitors, with PARP and ATR inhibitors showing efficacy in PBRM1-defective cancer cells, particularly in clear cell renal cell carcinomas, due to elevated replication stress, micronuclei, and R-loops..

Changed Anti-PD-1 monoclonal antibody in Solid tumours with PDCD1LG2 Amplification: 4

Comments changed: Case report. A patient with metastatic colon cancer and amplification of CD274 (PD-L1) and PDCD1LG2 (PD-L2) showed a durable response to nivolumab, but acquired resistance developed through outgrowth of cells lacking these amplifications, suggesting that combination therapies targeting both amplified and non-amplified cell populations might be more effective.. References changed: 3513517410.1200/PO.18.00017.

Changed Ripretinib in Gastrointestinal stromal tumour with PDGFRA D842V: 4

Comments changed: Preclinical study. Ripretinib, a switch-control kinase inhibitor, demonstrated efficacy against a broad spectrum of oncogenic and drug-resistant KIT and PDGFRA variants, particularly activation loop mutations, in cancer models..

Changed Imatinib, Sorafenib, Sunitinib in Gastrointestinal stromal tumour with PDGFRA V561D, D842_H845del: 4

Comments changed: Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842..

Changed Imatinib in Gastrointestinal stromal tumour with PDGFRA : 4

Alterations changed: V561D, N659K, D842Y, D842_I843delinsIM, D842_H845del, I843_H846del, Exon 18 deletion, Exon 12 mutation, Exon 14 mutationD842V. Comments changed: Preclinical study. Various PDGFRA mutations showed different in vitro sensitivity to imatinib, with exon 12 and 14 mutations being imatinib-sensitive, while most exon 18 mutations, particularly D842V, were imatinib-resistant, except for D842Y, D846Y, N848K, Y849K, and HDSN845-848P.Cell line study..

Changed Imatinib, Sunitinib in Gastrointestinal stromal tumour with PDGFRA W559_R560del: 4

Comments changed: Case report. A patient with gastrointestinal stromal tumor harboring a rare exon 12 PDGFRA mutation showed a dramatic response to sunitinib after relapsing on imatinib, suggesting sunitinib as a potential treatment option for this rare molecular subtype..

Changed Alpelisib in Solid tumours with PIK3CA Oncogenic mutations: 4

Comments changed: Phase Ia study. NCT01219699. Alpelisib showed preliminary activity in PIK3CA-altered solid tumors with ORR 6%, CBR 58%, and median PFS of 5.5 months in estrogen receptor-positive breast cancer.ORR 6%. CBR 58%..

Changed Ipatasertib in Solid tumours with PIK3CA : 4

Alterations changed: Kinase domain mutationsOncogenic mutations. Comments changed: Preclinical study. GDC-0068, a selective Akt inhibitor, showed antitumor activity in human cancer cells with markers of Akt activation, including PTEN loss and PIK3CA kinase domain mutations, and enhanced antitumor activity of chemotherapeutic agents..

Changed Pembrolizumab in Colorectal adenocarcinoma with POLE P286R: 4

Comments changed: Case report. A patient with POLE-mutated colorectal cancer and ultra-high tumor mutation burden experienced a complete and sustained response to pembrolizumab.Complete response.

Changed Olaparib in Diffuse Intrinsic Pontine Glioma with PPM1D Loss-of-function mutations: 4

Comments changed: Preclinical study. PPM1D-mutant DIPG cells showed sensitization to PARP inhibitor Olaparib when targeted with PPM1D inhibitor GSK2830371, impairing homologous recombination-mediated DNA repair..

Changed Ipatasertib in Solid tumours with PTEN Loss-of-function mutations: 4

Comments changed: Preclinical study. GDC-0068, a selective Akt inhibitor, showed antitumor activity in human cancer cells and xenograft models, with sensitivity correlated to PTEN loss and high-basal phospho-Akt levels..

Changed Sapanisertib + Metformin in Solid tumours with PTEN Loss-of-function mutations: 4

Comments changed: Phase 1 study. NCT03017833. Sapanisertib + metformin showed anti-tumor activity in patients with advanced solid tumors harbouring PTEN mutations and AKT/mTOR pathway alterations, with 4/30 patients achieving partial response, mostly with PTEN mutations..

Changed Trametinib in Histiocytosis with PTPN11 Oncogenic mutations, E72K: 4

Comments changed: Case report. Multifocal histiocytic sarcoma patient showed response to MEK inhibition with trametinib and tyrosine kinase inhibition with imatinib..

Changed Olaparib, Rucaparib in Ovarian cancer with RAD50 Oncogenic mutations; Deletions: 4

Comments changed: Preclinical study. RAD50 copy number deletion is associated with BRCAness and improved response to PARP inhibitors in BRCA wild-type ovarian cancer, with decreased RAD50 expression leading to enhanced sensitivity to cisplatin and olaparib.Cell line study.

Changed Olaparib in Solid tumours with RAD51C Oncogenic mutations: 4

Comments changed: Preclinical study. RAD51C-deficient cancer cells showed increased sensitivity to olaparib, with enhanced G2-M cell-cycle arrest and apoptosis, and RAD51C deficiency may be considered a biomarker for predicting olaparib's antitumor effects..

Changed Cobimetinib in Melanoma with RAF1 Fusion; GOLGA4-RAF1 fusion: 4

Comments changed: Case report. A metastatic melanoma patient with a GOLGA4-RAF1 fusion and resistance to anti-CTLA4/anti-PD1 combination immunotherapy showed a profound response to MEK inhibitor therapy, indicating the potential of thorough molecular characterization to identify therapeutic targets in treatment-resistant cancers harbouring specific mutations..

Changed Trametinib in Non-small cell lung cancer with RASA1 Loss-of-function mutations; Oncogenic mutations: 4

Comments changed: Preclinical study. RASA1 and NF1 co-mutations define a distinct subset of NSCLC, associated with sensitivity to MEK inhibition, particularly with concurrent loss-of-function mutations..

Changed LY3295668 in Solid tumours with RB1 Oncogenic mutations, Loss-of-function mutations, loss of protein expression: 4

Comments changed: Preclinical study. Loss-of-function mutations in RB1 gene are common in several treatment-refractory cancers. AURKA inhibitor LY3295668 showed cytotoxic effects in RB1-deficient cancer cells and led to durable regression of RB1(mut) tumor xenografts..

Changed Taletrectinib in Non-small cell lung cancer with ROS1 Fusions; G2032R: 4

Comments changed: Preclinical study. DS-6051b, a selective ROS1/NTRK inhibitor, showed growth inhibition in ROS1-rearranged cancers with crizotinib-resistant G2032R mutation, overcoming resistance to crizotinib, lorlatinib, and entrectinib..

Changed Cabozantinib in Non-small cell lung cancer with ROS1 G2032R: 4

Comments changed: Preclinical study and case report highlighting ROS1-rearranged NSCLC with secondary resistance mutation, where cabozantinib overcomes crizotinib resistance by effectively inhibiting ROS1 wild-type and resistant mutants, including G2032R mutation.Cell-line evidence only.

Changed Taletrectinib, Repotrectinib, NVL-520 in Solid tumour with ROS1 G2032R: 4

Comments changed: Preclinical study. NVL-520 is a selective and brain-penetrant inhibitor of ROS1 fusions and secondary resistance mutations, showing potent targeting of ROS1 and diverse ROS1 resistance mutations with high selectivity for ROS1 G2032R over TRK..

Changed Crizotinib in Non-small cell lung cancer with ROS1 SLC12A2-ROS1 fusion: 4

Comments changed: Case report. Novel SLC12A2-ROS1 fusion identified in NSCLC patient, who showed significant response to crizotinib, highlighting the importance of choosing the appropriate next-generation sequencing assay..

Changed Crizotinib, Entrectinib, Loratinib, Taletrectinib, Repotrectinib, NVL-520 in Solid tumour with ROS1 SLC34A2-ROS1 fusion, EZR-ROS1 fusion, CD74-ROS1 fusion, GOPC-ROS1 fusion, CEP85L-ROS1 fusion: 4

Comments changed: Preclinical study. NVL-520 showed potent targeting of ROS1 and diverse ROS1 resistance mutations with high selectivity for ROS1 G2032R over TRK and brain penetration.Cell-line study.

Changed H3B-8800 in Solid tumours, Liquid cancers with SF3B1 Oncogenic mutations: 4

Comments changed: Preclinical study. H3B-8800, an orally available splicing modulator, preferentially kills spliceosome-mutant cancer cells bearing mutations in SF3B1, U2AF1, and SRSF2 by retaining short, GC-rich introns, with loss of activity observed in drug-resistant cells with mutations in SF3b components..

Changed Tazemetostat in Ovarian small cell carcinoma with SMARCA4 Loss of protein expression: 4

Comments changed: Preclinical study. Tazemetostat, an EZH2 inhibitor, showed antiproliferative and antitumor effects in SMARCA2- and SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) cell lines and xenografts, indicating EZH2 dependence in this subset of tumors with SWI/SNF mutations..

Changed Palbociclib in Ovarian small cell carcinoma with SMARCA4 Loss-of-function mutations: 4

Comments changed: Preclinical study. SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) cells with downregulated cyclin D1 are sensitive to CDK4/6 inhibitors, suggesting a potential therapeutic application for CDK4/6 inhibitors in SCCOHT with SMARCA4 inactivating mutations..

Changed Imatinib, Sunitinib in Gastrointestinal stromal tumour with PDGFRA D842V

Tier changed: R2R1. Comments changed: Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842.OncoKB R1 but not blacklisted by TGA.

Changed Therapy in Solid tumours with BRAF Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R: R2

Therapy changed: FORE8394PLX8394.

Changed Vemurafenib, Dabrafenib in Solid tumours with BRAF Class III mutations, D287H, V459L, G466V, G466E, G466A, S467L, N581S, N581I, D594N, D594G, D594A, D594H, F595L, G596D, G596R: R2

Comments changed: Class III mutations. Preclinical study. Tumours with class 3 BRAF mutants, characterized by impaired kinase activity or kinase-dead mutants, are sensitive to inhibition of RAS activation, particularly in the presence of coexistent mechanisms for maintaining RAS activation, such as RAS mutations or receptor tyrosine kinase signalling..

Changed Therapy in Melanoma with BRAF Fusions, FKBP15-BRAF fusion, TARDBP-BRAF fusion, AGK-BRAF fusion, SKAP2-BRAF fusion, CUL1-BRAF fusion, KIAA1549-BRAF fusion: R2

Therapy changed: Vemurafenib, Dabrafenib, FORE8394Vemurafenib, Dabrafenib, PLX8394. Comments changed: Preclinical study. BRAF fusion-positive melanoma cell lines showed heterogeneous responses to RAF and MEK inhibitors, with higher expression levels and dimerization domains associated with resistance and paradoxical MAPK pathway activation, while next-generation RAF inhibitors and combination with MEK inhibitors showed increased therapeutic activity..

Changed Vemurafenib in Solid tumours with BRAF N486_P490del: R2

Comments changed: Preclinical study. Activating in-frame deletions in protein kinases BRAF, EGFR, and HER2 drive cancer, with crystal structures revealing a mechanism of activation and resistance to certain inhibitors, such as vemurafenib..

Changed Therapy in Glioma with BRAF V600E and L514V: R2

Therapy changed: Vemurafenib, Dabrafenib, FORE8394Vemurafenib, Dabrafenib, PLX8394.

Changed Afatinib, Poziotinib, Tarloxotinib in Non-small cell lung cancer with EGFR Exon 20 insertion and T790M and C797S: R2

Comments changed: Preclinical study. Cell line study. Tarloxotinib-E showed efficacy against Ba/F3 cells with EGFR exon 20 mutations, but acquired resistance was observed through T790M or C797S secondary mutations, depending on the original EGFR exon 20 mutation..

Changed Tarloxotinib in Non-small cell lung cancer with EGFR H773insH: R2

Comments changed: Preclinical study. Cell line study. Tarloxotinib-E showed efficacy against Ba/F3 cells with various EGFR exon 20 mutations, and acquired resistance to tarloxotinib-E was associated with secondary T790M or C797S mutations, influenced by the original EGFR exon 20 mutation..

Changed Afatinib in Non-small cell lung cancer with EGFR H773L and V774M: R2

Comments changed: Case report. A rare EGFR H773L/V774M compound mutation in NSCLC showed primary resistance to afatinib, suggesting it may be one of the EGFR-TKI-resistant uncommon EGFR mutations..

Changed Osimertinib in Non-small cell lung cancer with EGFR : R2

Alterations changed: L718V, L718Q, G719. Comments changed: Case report. Acquired EGFR L718V mutation identified as a resistance mechanism to osimertinib in a T790M-negative NSCLC patient, providing insight into osimertinib resistance.OncoKB R2 (concordant). References changed: 29506987, 31301016.

Changed Osimertinib in Non-small cell lung cancer with EGFR : R2

Alterations changed: L718V, L718Q, L792L747P. Comments changed: Novel secondary EGFR mutations L718 and L792 confer osimertinib resistance in NSCLC patients, with L718Q conferring the greatest resistance, and parallel or downstream oncogene alterations also contributing to resistance.Case report. References changed: 2950698729673089.

Changed Gefitinib, Erlotinib in Non-small cell lung cancer with EGFR L747P, L747S: R2

Comments changed: Preclinical and clinical study. Afatinib showed efficacy in treating lung adenocarcinoma with uncommon EGFR p.L747P and p.L747S mutations with 80% ORR and 11.97 months median PFS, and no patients acquired p.T790M resistance after afatinib failure..

Changed AZD4547 in Solid tumours with FGFR2 Oncogenic mutations and NOT Amplification

Tier changed: R24. Comments changed: Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions.No response in this cohort.

Changed Infigratinib in Cholangiocarcinoma with FGFR2 V564F, N549H, N549K, E565A, L617V, K641R, K659M: R2

Comments changed: Preclinical study and case series. Polyclonal secondary FGFR2 mutations in the kinase domain were identified in cfDNA and biopsies of FGFR2 fusion-positive cholangiocarcinoma patients, driving acquired resistance to FGFR inhibitor BGJ398, and were surmountable by distinct FGFR inhibitors..

Changed Osimertinib, Gefitinib in Non-small cell lung cancer with FGFR3 FGFR3-TACC3 fusion: R2

Comments changed: Retrospective observational study. FGFR2/3 fusions, particularly FGFR3-TACC3, were identified as a rare acquired resistance mechanism in advanced NSCLC patients treated with EGFR TKIs, and combining EGFR TKIs with FGFR TKIs showed clinical benefit in patients with FGFR3-TACC3 fusions..

Changed Osimertinib in Non-small cell lung cancer with FGFR3 Fusion: R2

Comments changed: Retrospective observational study. Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy revealed various mechanisms of resistance, with EGFR T790M mutation being the most common (63%), followed by MET amplification (5%), HER2 amplification (13%), and small cell transformation (3%), also including small number of off-target mechanism such as FGFR3 fusion..

Changed Infigratinib, AZD4547, Zoligratinib in Cholangiocarcinoma with FGFR3 N540K, V555M, L608V: R2

Comments changed: Preclinical study and case series. Polyclonal secondary FGFR2 mutations in the kinase domain were identified in cfDNA and biopsies of FGFR2 fusion-positive cholangiocarcinoma patients, driving acquired resistance to FGFR inhibitor BGJ398, and were surmountable by distinct FGFR inhibitors..

Changed Pemigatinib in Non-small cell lung cancer with FGFR3 V555M, V555L: R2

Comments changed: Phase2 FIGHT-207 basket trial. NCT03822117. Pemigatinib showed ORR of 26.5% and 9.4% in patients with FGFR fusions/rearrangements and activating non-kinase domain mutations respectively, with TP53 co-mutations associated with lack of response and BAP1 alterations with higher response rates, while FGFR1-FGFR3 gatekeeper and molecular brake mutations led to acquired resistance.Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib..

Changed Fisogatinib in Solid tumours, Hepatocellular carcinoma with FGFR4 V550E, V550L: R2

Comments changed: Preclinical and clinical study. On-target FGFR4 kinase domain mutations were identified as a mechanism of acquired resistance to fisogatinib in HCC patients with aberrant FGF19 expression, validating FGFR4 as an oncogenic driver.Gatekeeper mutation.

Changed Sunitinib in Colorectal adenocarcinoma with FLT3 Amplification: R2

Comments changed: Phase 2 TAPUR basket study. NCT02693535. Sunitinib showed no clinical activity in patients with metastatic colorectal cancer with FLT-3 amplification, as no objective responses were observed (ORR 0%) and only two patients had stable disease at 16 weeks, suggesting FLT-3 amplification may not be a sufficient target for sunitinib.NCT02693535. TAPUR. ORR 0%..

Changed Sorafenib in Acute myeloid leukaemia with FLT3 D835: R2

Comments changed: Clinical study. Relapsed or refractory FLT3-ITD(+) AML patients treated with sorafenib showed initial response but subsequent resistance was associated with the emergence of D835 mutation in leukemia initiating cells, suggesting selection of more aggressive subclones carrying both FLT3-ITD and D835 mutations..

Changed Vismodegib in Basal cell carcinoma with GLI1 Overexpression: R2

Comments changed: Preclinical study. Genomic analysis of basal cell carcinoma revealed that Smoothened (SMO) inhibitor resistance is associated with Hedgehog pathway reactivation through SMO mutations that impair drug binding, and copy number changes in SUFU and GLI2..

Changed Vismodegib in Basal cell carcinoma with GLI2 Overexpression: R2

Comments changed: Preclinical studies. Genomic analysis of basal cell carcinoma tumors and a medulloblastoma patient treated with vismodegib revealed that acquired resistance to Smoothened antagonists occurs through Hedgehog pathway reactivation via SMO mutations that either impair drug binding or constitutively activate SMO..

Changed Osimertinib in Non-small cell lung cancer with GNAS R201C, R201H: R2

Comments changed: Case report. A NSCLC patient with osimertinib resistance harboring GNAS R201C and R201H mutations showed stable disease after treatment with trametinib, suggesting GNAS R201 mutations confer osimertinib resistance and trametinib as a potential treatment option..

Changed MEK inhibitor in Gastric cancer with HGF Overexpression: R2

Comments changed: Preclinical study. Overexpression of HGF induces resistance to c-MET tyrosine kinase inhibitors in gastric cancer cells through an autocrine manner, despite c-MET TKIs inhibiting downstream signaling and cell proliferation..

Changed Sonidegib, Vismodegib in Solid tumours with HRAS G12V: R2

Comments changed: Preclinical study. RAS/MAPK pathway activation drives off-target mechanism of resistance to Smo inhibition, with Sufu mutations maintaining Shh pathway activity and emerging RAS/MAPK activation in Smo inhibitor-treated BCC patients..

Changed Ivosidenib in Acute myeloid leukaemia with IDH1 S280F: R2

Comments changed: Phase 1 trial. NCT02074839. N=174. Multiple mechanisms of resistance to ivosidenib were identified in IDH1-mutant relapsed/refractory AML, including RTK pathway mutations associated with primary resistance, and second-site IDH1 mutations and IDH2 mutations restoring 2-HG production associated with acquired resistance..

Changed Ruxolitinib in Liquid cancers with JAK1 F958V, F958C, P960: R2

Comments changed: Preclinical study. Cell line study identified JAK1 and JAK2-activating mutations, specifically those targeting F958 and P960 in JAK1 and Y931 in JAK2, confer resistance to ATP-competitive JAK inhibitors.Cell line study..

Changed Ruxolitinib in Liquid cancers with JAK2 Y931C, Y931C and V617F: R2

Comments changed: Preclinical study. Cell line study identified JAK1 and JAK2-activating mutations, specifically those targeting F958 and P960 in JAK1 and Y931 in JAK2, confer resistance to ATP-competitive JAK inhibitors.Cell line study..

Changed Imatinib in Melanoma with KIT Amplification: R2

Comments changed: Phase 2 trial. Imatinib demonstrates efficacy in melanomas with KIT mutations (54% response rate) but shows no response in tumors with KIT amplification only (0% ORR). KIT mutation status serves as a predictor of response, while NRAS mutations and KIT copy number gain are associated with imatinib resistance.ORR 0% in KIT amplification only.

Changed Sorafenib in Gastrointestinal stromal tumour with KIT D816F, D816G, D816H, D816V, D816: R2

Comments changed: Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842. (Merged 2025-05-28)Secondary resistance.

Changed Therapy in Gastrointestinal stromal tumour with KIT NOT Oncogenic mutations, V654A, T670I: R2

Therapy changed: BezuclastinibPLX9486. Comments changed: Phase 1b/2a trial. NCT02401815. In refractory GIST, the combination of Bezuclastinib (type I KIT inhibitor) and sunitinib (type II KIT inhibitor) demonstrated a median PFS of 12.1 months and clinical benefit rate of 80%. KIT wildtype tumors and those harboring V654A or T670I mutations showed lack of sensitivity to this combination therapy..

Changed Cabozantinib in Gastrointestinal stromal tumour with KIT V559A, V559D, D816H, D816V: R2

Comments changed: Preclinical study. Cabozantinib, a MET and VEGFR2 inhibitor, suppresses metastasis, angiogenesis, and tumor growth by inhibiting MET and VEGFR2 phosphorylation, with potential therapeutic application in cancers with dysregulated MET and VEGFR signaling. Drug sensitivity screen revealed relative insensitivity of KIT V559A, V559D, D816H, D816V to Cabozantinib.Drug sensitivity screen..

Changed Imatinib + Binimetinib in Gastrointestinal stromal tumour with KIT V654A, N822K, N822Y, D820G: R2

Comments changed: Phase 2 trial. NCT01991379. Imatinib plus Binimetinib showed a high ORR of 69% in treatment-naive advanced GIST patients, with 29 of 42 evaluable patients achieving confirmed PR, and median PFS of 29.9 months. Emergent secondary KIT mutations and CDKN2A alterations associated with resistance were identified..

Changed Midostaurin in Gastrointestinal stromal tumour with KIT V654A, T670I: R2

Comments changed: Preclinical study. ATP-competitive inhibitors midostaurin and avapritinib displayed distinct resistance profiles in exon 17-mutant KIT, with avapritinib being selectively problematic for T670I gatekeeper mutation, conferring resistance indirectly through conformational changes..

Changed Pemigatinib in Cancer of unknown primary with KRAS A59T, G13D: R2

Comments changed: Phase 2 FIGHT-207 basket trial. NCT03822117. Pemigatinib showed ORR of 27% and 9% in cohorts with FGFR fusions/rearrangements and activating non-kinase domain mutations, respectively, with TP53 co-mutations associated with lack of response and BAP1 alterations with higher response rates, and identified FGFR1-FGFR3 gatekeeper and molecular brake mutations as acquired resistance mechanisms. Acquired resistance mutations following Pemigatinib were identified.Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib..

Changed Binimetinib + Encorafenib in Colorectal adenocarcinoma with KRAS Amplification: R2

Comments changed: Preclinical study and paired pre-post treatment sequencing. Identified alterations in MAPK pathway genes, including KRAS amplification, in resistant BRAF-mutant colorectal cancer tumors post-RAF inhibitor combination treatment..

Changed Cetuximab, Panitumumab in Colorectal adenocarcinoma with KRAS Amplification: R2

Comments changed: Preclinical study and patient sample analysis. KRAS amplification, detected in 0.67% of 1039 CRC specimens, is associated with primary resistance to EGFR-targeted therapy, with tumors or cell lines harboring this lesion being non-responsive to anti-EGFR inhibitors.Cell line study. Tumors or cell lines harboring KRAS amplification are not responsive to anti-EGFR inhibitors..

Changed Dabrafenib + Panitumumab in Colorectal adenocarcinoma with KRAS Amplification: R2

Comments changed: Preclinical study. Identified alterations in MAPK pathway genes, including KRAS amplification, in paired pretreatment and postprogression tumor biopsies from patients with BRAF-mutant colorectal cancer treated with RAF inhibitor combinations, driving clinical acquired resistance.Paired pre-post treatment sequencing.

Changed Crizotinib in Non-small cell lung cancer with KRAS Amplification: R2

Comments changed: Biomarker analysis. Co-occurring RAS-MAPK pathway alterations, notably in KRAS and NF1, were associated with decreased response to MET inhibitor treatment in MET exon 14 skipping mutation-positive lung cancer.Case series..

Changed Trametinib in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with KRAS Amplification and NOT missense variant: R2

Comments changed: Preclinical study. KRAS amplification in gastroesophageal cancer models results in insensitivity to MEK inhibition due to adaptive increase in KRAS-GTP levels, but combined MEK and SHP2 inhibition shows enhanced sensitivity, revealing a potential therapeutic strategy for KRAS-amplified tumors.Intrinsic resistance to MEK inhibitor.

Changed Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with KRAS Amplification, G12A, G12D, G12R, G12V, G13D, R68S, H95R, Y96D, Y96H, Y96N, Q99L, A146T, Oncogenic mutation AND NOT G12C: R2

Comments changed: Phase 1/2 single arm trial. GO42144. NCT04449874. Divarasib showed confirmed response rates of 53% in NSCLC and 29% in colorectal cancer patients. Serial ctDNA assessment identifying genomic alterations associated with response and potential acquired and treatment-emergent mutations.Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations.

Changed Crizotinib in Non-small cell lung cancer with KRAS Amplification, G12D: R2

Comments changed: Biomarker analysis. Study on MET exon 14-mutant NSCLC. Acquired resistance to MET TKIs driven by on-target secondary MET mutations (35%) and off-target mechanisms including KRAS mutations (45%).Off-target resistance.

Changed Trastuzumab in Gastric cancer with KRAS Amplification, G13D, A146V: R2

Comments changed: Case-control study. AMNESIA. Biomarkers of primary resistance to trastuzumab in HER2-positive metastatic gastric cancer patients, showing significant association between presence of genomic alterations (including KRAS mutations/amplifications) and primary resistance, with median PFS 2.6 months versus 5.2 months..

Changed Osimertinib in Non-small cell lung cancer with KRAS G12S: R2

Comments changed: Preclinical study and patient biopsy analysis. Heterogeneous mechanisms of resistance to third-generation EGFR inhibitors, including MET or ERBB2 amplification and KRAS(G12S) mutation, suggesting potential combination strategies such as EGFR/MEK dual inhibition to overcome resistance.Secondary resistance post Osimertinib.

Changed Sotorasib in Non-small cell lung cancer with KRAS G12V: R2

Comments changed: Phase 1/2 study findings. Multiple treatment-emergent alterations observed in 27 patients treated with sotorasib, including alterations in KRAS, NRAS, BRAF, and other genes, associated with resistance to KRAS(G12C) inhibition.Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models..

Changed Cetuximab, Cetuximab + Irinotecan in Colorectal adenocarcinoma with KRAS G13D: R2

Comments changed: Phase 2 ICECREAM trial. N=51. Response rate was 0% with cetuximab monotherapy versus 9% with cetuximab plus irinotecan in patients with KRAS G13D mutation-positive metastatic colorectal cancer.ORR 0% in G13D mutant mCRC.

Changed Osimertinib in Non-small cell lung cancer with KRAS G13D: R2

Comments changed: Preclinical study. KRAS G13D mutation was found in PC9-AZDR clones, conferring acquired resistance to mutation-selective EGFR tyrosine kinase inhibitors in non-small cell lung cancer cells.Cell line data. Off-target resistance.

Changed Osimertinib in Non-small cell lung cancer with KRAS Oncogenic mutations: R2

Comments changed: Biomarker analysis. In 155 tumor specimens with acquired EGFR-TKI resistance, mechanisms included EGFR T790M mutation (63%), HER2 amplification (13%), MET amplification (5%), and small cell transformation (3%), among others.Off-target mechanism.

Changed SHP099 in Pancreatic acinar cell carcinoma with KRAS Q61H: R2

Comments changed: Preclinical study. The Q61H mutation in KRAS confers resistance to SHP2 inhibitors by decoupling KRAS from upstream regulation, impairing GTP hydrolysis, and retaining high-affinity RAF interaction..

Changed Crizotinib in Non-small cell lung cancer with KRAS+MET MET:exon 14 skipping mutation and KRAS:Oncogenic mutations: R2

Comments changed: KRAS mutation is identified as a mechanism of primary and secondary resistance to MET tyrosine kinase inhibitors in MET exon 14-mutant non-small cell lung cancer, with dual inhibition of MET or EGFR/ERBB2 and MEK showing potential as a therapeutic approach..

Changed Cetuximab, Panitumumab in Colorectal adenocarcinoma with MAP2K1 K757E, K57N: R2

Comments changed: RTK alterations and MAP2K1 mutations occur in approximately 8% of colorectal carcinoma cases, often associated with wild-type RAS/RAF, and confer resistance to anti-EGFR and/or anti-ERBB2 therapy..

Changed Trametinib in Histiocytosis with MAP2K1 L98_K104delinsQ: R2

Comments changed: Preclinical study. MAP2K1 L98_K104delinsQ identified in Langerhans cell histiocytosis confers resistance to MEK inhibitor trametinib and causes auto-activation of ERK pathway in vitro..

Changed Selumetinib in Melanoma with MAP2K1 P124L, Q56P: R2

Comments changed: Preclinical study. MEK1 mutations, particularly those affecting the allosteric drug binding pocket, alpha-helix C, and N-terminal negative regulatory helix (helix A), confer resistance to MEK and B-RAF inhibition in BRAF-mutant melanoma..

Changed Vemurafenib, Dabrafenib in Melanoma with MAP2K1+BRAF MAP2K1:P124 and BRAF:V600: R2

Comments changed: Retrospective analysis. 123 patients with BRAF V600-mutant metastatic melanoma showed preexisting MEK1 P124 mutations (N=12, 10%) were associated with poorer RECIST response (33% vs 72%) and shorter PFS (3.1 vs 4.8 months), indicating a subset of patients likely to benefit from combination therapies involving MEK or ERK inhibitors due to intrinsic resistance mechanism..

Changed Cetuximab, Panitumumab in Colorectal adenocarcinoma with MET Amplification: R2

Comments changed: Preclinical study. Amplification of the MET gene is associated with acquired resistance to EGFR targeted therapy in patients with metastatic colorectal cancer; MET inhibitors could be effective in overcoming this resistance..

Changed Gefitinib, Erlotinib, Afatinib, Dacomitinib, Osimertinib in Non-small cell lung cancer with MET Amplification: R2

Comments changed: Preclinical and clinical study. Clonal MET amplification, observed in 3% of treatment-naive EGFR-mutant NSCLC, was associated with suboptimal response to EGFR TKI, highlighting its role as a determinant of TKI resistance..

Changed Trastuzumab in Gastric cancer with MET Amplification, N375S: R2

Comments changed: Case-control study (AMNESIA). Identified biomarkers (EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications) associated with primary resistance to trastuzumab in HER2-positive metastatic gastric cancer patients, with significantly shorter PFS (2.6 vs 5.2 months) and OS (7.6 vs 16.1 months)..

Changed Crizotinib in Non-small cell lung cancer with MET D1228N (D1246N): R2

Comments changed: Case report. Acquired D1228N mutation in MET kinase domain identified as a potential resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping using targeted next-generation sequencing..

Changed Crizotinib in Triple-negative breast cancer with MET D1228N (D1246N): R2

Comments changed: Case report. MET D1228N mutation emerged during progression on crizotinib in MET-amplified triple-negative breast cancer, conferring resistance to crizotinib but retaining sensitivity to cabozantinib..

Changed Capmatinib, Tepotinib, Savolitinib in Non-small cell lung cancer with MET D1228N (D1246N), D1228 (D1246): R2

Comments changed: On-target secondary MET kinase domain mutations and off-target mechanisms including KRAS mutations and amplifications in KRAS, EGFR, HER3, and BRAF drive resistance to MET TKIs in MET exon 14-mutant NSCLC..

Changed Glesatinib in Non-small cell lung cancer with MET H1094Y (H1112Y), L1195V (L1213V): R2

Comments changed: Preclinical study. Study analysed tissue or plasma NGS data from 20 MET exon 14-mutant NSCLC patients at the time of MET TKI resistance, identifying on-target (MET kinase domain mutations, MET exon 14-mutant allele amplification) and off-target (KRAS mutations, EGFR, HER3, BRAF amplifications) resistance mechanisms in 75% of patients..

Changed Infigratinib, AZD4547, Rogaratinib in Gastric cancer with MET Overexpression: R2

Comments changed: Preclinical studies on FGFR1-amplified lung cancer cell lines identified diverse mechanisms of primary and acquired drug resistance to FGFR inhibitors, including NRAS amplification, DUSP6 deletion, and MET upregulation/amplification, which reactivate MAPK pathway and confer resistance, suggesting rational combination therapies to improve FGFR inhibitor treatments.PDX models; Off-target mechanism. References changed: 28630215, 2742907328630215; 27429073.

Changed Crizotinib in Non-small cell lung cancer with MET Y1230H (Y1248H): R2

Comments changed: Case report. Preexisting MET Y1230C mutation confers acquired resistance to crizotinib in NSCLC with MET exon 14 skipping, detected at low frequency pretreatment and in ctDNA at progression.Case report. Acquired resistance.

Changed Crizotinib in Non-small cell lung cancer with MET Y1230S (Y1248S), D1228N (D1246N), D1228H (D1246H), F1200I (F1218I), L1195V (L1213V), S244fs: R2

Comments changed: Retrospective analysis. Targeted sequencing analysis of 289 patients with METex14-mutated NSCLC revealed co-occurring RAS-MAPK pathway alterations associated with decreased MET TKI treatment response, and preclinical models showed that combining crizotinib with MEK inhibitor trametinib overcame this resistance.Case series..

Changed Crizotinib in Non-small cell lung cancer with MET+TP53 MET:Exon 14 skipping mutation and TP53:Oncogenic mutations: R2

Comments changed: Case series. Co-occurring RAS-MAPK pathway alterations (e.g., KRAS, NF1) are associated with decreased response to MET inhibitors in METex14-mutated NSCLC. Combined inhibition of MET and MEK signaling overcomes this resistance in preclinical models. TP53 mutation was observed in 7 of 12 cases following crizotinib exposure.Case series. TP53 mutation shown in post-exposure to crizotinib 7 of 12 cases..

Changed Atezolizumab, Atezolizumab + Cobimetinib in Colorectal adenocarcinoma with Microsatellite Instability Stable: R2

Comments changed: Phase 3 IMblaze370 trial. NCT02788279. Atezolizumab with or without cobimetinib did not improve OS versus regorafenib in microsatellite-stable metastatic colorectal cancer, with an ORR of 4/273 (1%) in the atezolizumab groups, highlighting the challenge of expanding immunotherapy benefits to tumours with lower baseline immune inflammation.Phase 3. IMBlaze370. ORR 4/273 (1%) in the Atezolizumab groups..

Changed Durvalumab in Endometrial cancer with Microsatellite Instability Stable: R2

Comments changed: Phase 2 trial. PHAEDRA. NCT03015129. Durvalumab demonstrated an objective tumor response rate of 47% in mismatch repair-deficient (dMMR) endometrial cancer versus 3% (1 of 35) in mismatch repair-proficient (pMMR) tumors, with median progression-free survival of 1.8 months in the pMMR group.PHAEDRA. Phase 2. ORR in the pMMR cohort was 3% (1 of 35) with median PFS of 1.8 months..

Changed FOLFOX + Bevacizumab + Durvalumab + Oleclumab in Colorectal adenocarcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: R2

Comments changed: Phase 1B/2. COLUMBIA-1. NCT04068610. N=59. Durvalumab + oleclumab added to FOLFOX and bevacizumab did not significantly improve ORR (62% vs 46%) in metastatic microsatellite-stable colorectal cancer.Phase 1B/2. COLUMBIA-1. NCT04068610. N=59. Durvalumab + oleclumab added to FOLFOX and bevacizumab did not significantly improve ORR (61.5% vs 46.2%) in metastatic microsatellite-stable colorectal cancer..

Changed Nivolumab + FLOX in Colorectal adenocarcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: R2

Comments changed: Randomized Phase 2. METIMMOX trial. NCT03388190. N=80. In microsatellite stable disease, alternating FLOX + nivolumab showed no PFS advantage over FLOX alone (9.2 months each).Randomized Phase 2. METIMMOX trial. NCT03388190. N=80. In microsatellite stable disease, no PFS advantage was observed with alternating FLOX + nivolumab over FLOX alone (both 9.2 months)..

Changed Androgen receptor antagonist, GnRH agonist, CYP17A1 inhibitor, Enzalutamide, Apalutamide in Prostate cancer with MYCN Amplification: R2

Comments changed: Preclinical study. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer, highlighting restored AR signalling, AR bypass signalling, and complete AR independence as potential resistance mechanisms.Off-target mechanism.

Changed Crizotinib in Non-small cell lung cancer with NF1 Oncogenic mutations: R2

Comments changed: Preclinical study and cfDNA analysis of 289 patients showed co-occurring RAS-MAPK pathway alterations limit response to MET inhibitors in MET exon 14 skipping mutation-positive lung cancer, and resistance was overcome by combining crizotinib with MEK inhibitor trametinib.Case series..

Changed Imatinib in Melanoma with NRAS Amplification: R2

Comments changed: Phase 2 trial of imatinib in metastatic melanoma with KIT amplifications and/or mutations, showing effectiveness in tumors with KIT mutations (54% response rate) but not in those with KIT amplifications only, with potential resistance mechanisms including NRAS mutations and KIT copy number gain..

Changed Larotrectinib in Solid tumours with NTRK1 High mRNA expression

Tier changed: R24. Comments changed: Phase 2 trial. ACTRN12619001147178. Larotrectinib showed limited efficacy in tumors with NTRK overexpression (ORR 0%).. References changed: 39720993ACTRN12619001147178.

Changed Larotrectinib in Solid tumours with NTRK2 High mRNA expression

Tier changed: R24. Comments changed: Phase 2 trial. ACTRN12619001147178. Larotrectinib showed limited efficacy in tumors with NTRK overexpression (ORR 0%).. References changed: 39720993ACTRN12619001147178.

Changed Larotrectinib in Solid tumours with NTRK3 High mRNA expression

Tier changed: R24. Comments changed: Phase 2 trial. ACTRN12619001147178. Larotrectinib showed limited efficacy in tumors with NTRK overexpression (ORR 0%).. References changed: 39720993ACTRN12619001147178.

Changed Talazoparib in Lung squamous cell carcinoma with PALB2 Oncogenic mutations: R2

Comments changed: Phase 2 S1400G study. NCT02154490. Talazoparib demonstrated limited activity in homologous recombination repair-deficient squamous cell lung cancer with ORR of 4% in primary analysis population and 11% in full eligible population.Lung-MAP Substudy S1400G. ORR primary population 4%.

Changed Imatinib in Gastrointestinal stromal tumour with PDGFRA

Alterations changed: D842VV561D, N659K, D842Y, D842_I843delinsIM, D842_H845del, I843_H846del, Exon 18 deletion. Tier changed: R24. Comments changed: Preclinical study. Various PDGFRA mutations showed different in vitro sensitivity to imatinib, with exon 12 and 14 mutations being imatinib-sensitive, while most exon 18 mutations, particularly D842V, were imatinib-resistant, except for D842Y, D846Y, N848K, Y849K, and HDSN845-848P. (Entry updated/corrected 2025-05-28.)Cell line study..

Changed Imatinib, Sorafenib, Sunitinib in Gastrointestinal stromal tumour with PDGFRA D842V: R2

Comments changed: Preclinical study. Sorafenib inhibits various KIT and PDGFRA kinase mutations associated with imatinib and sunitinib resistance in gastrointestinal stromal tumors, except for substitutions at KIT codon D816 and PDGFRA codon 842..

Changed Imatinib, Nilotinib, Sorafenib in Chronic eosinophilic leukaemia with PDGFRA FIP1L1-PDGFRA fusion and T674I: R2

Comments changed: Case report. A patient with FIP1L1-PDGFRA-positive chronic eosinophilic leukemia developed imatinib resistance due to T674I mutation, and showed limited clinical activity to subsequent nilotinib and sorafenib treatments..

Changed Imatinib in Mastocytosis with PDGFRA : R2

Alterations changed: FIP1L1-PDGFRA fusion and T674I. Comments changed: FIP1L1-PDGFRA fusion tyrosine kinase is identified as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome, with relapse correlating with the appearance of a T674I mutation in PDGFRA that confers resistance to imatinib.Primary resistance.

Changed Olaratumab in Soft tissue sarcomas with PDGFRA Protein expression: R2

Comments changed: Preclinical study. Olaratumab, a PDGFRA antibody, showed no significant antitumor effects as a single agent or in combination with doxorubicin in a panel of patient-derived soft tissue sarcoma xenografts.Negative Xenograft data.

Changed Osimertinib in Non-small cell lung cancer with PIK3CA G118D: R2

Comments changed: Preclinical study. Amplification of EGFR wild-type alleles was found to confer acquired resistance to mutation-selective EGFR tyrosine kinase inhibitors, with the Src-AKT pathway also contributing to resistance.Cell line data. Off-target resistance.

Changed Trametinib in Pancreatic acinar cell carcinoma with RAF1 Fusion; GATM-RAF1 fusion: R2

Comments changed: Case report. Pancreatic acinar cell carcinoma with RAF1 fusion demonstrated inferior response to MEK inhibitor therapy with no objective response. Concomitant CDKN2A loss was reported.No objective response seen. Concomitant mutations reported including CDKN2A loss.

Changed Therapy in Low-grade gliomas with RAF1 Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion: R2

Therapy changed: Vemurafenib, FORE8394Vemurafenib, PLX8394.

Changed Adagrasib in Solid tumours with RAF1 RAF1-CCDC176 fusion, RAF1-TRAK1 fusion, Fusions: R2

Comments changed: Phase 1/2. KRYSTAL-1. Off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of Adagrasib exposure, detected via tissue or ctDNA from blood samples. Acquired resistance to KRAS(G12C) inhibitors occurs through diverse genomic and histologic mechanisms, including acquired KRAS alterations, bypass mechanisms such as MET amplification and oncogenic fusions, and histologic transformation.Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample..

Changed Vandetanib in Solid tumours with RET G810A: R2

Comments changed: Preclinical study. KIF5B-RET fusion lung adenocarcinoma modeled in transgenic mice and cell lines, showing ponatinib as the most effective inhibitor against KIF5B-RET and its drug-resistant mutants, and identifying novel vandetanib-resistant RET(G810A) mutation..

Changed Selpercatinib in Non-small cell lung cancer with RET G810A, G810S, G810C, G810R: R2

Comments changed: Preclinical study and Case report. RET G810 solvent front mutations mediate acquired resistance to selpercatinib in RET-driven malignancies through steric hindrance of drug binding.Case report and xenograft studies. Acquired resistance after treatment with Selpercatinib as a result by steric hinderance of drug binding..

Tuesday, 27 May 2025 (Version: 20250527AU)

New Adagrasib + Cetuximab in Colorectal adenocarcinoma with KRAS G12C: 3

Phase 1/2 trial. N=94. Adagrasib + cetuximab in KRASG12C-mutated metastatic colorectal cancer. ORR: 34%. Median PFS: 6.9 months. Median OS: 15.9 months. Grade 3-4 TRAEs in 27.7% patients. No TRAEs led to adagrasib discontinuation. References: 38587856

New ABBV-637 + Osimertinib in Non-small cell lung cancer with EGFR Oncogenic mutation: 4

Phase 1 dose escalation and expansion. NCT04721015. ABBV-637 plus osimertinib showed clinical activity with ORR of 14% and 10% in 3rd-line and 2nd-line therapy respectively, and a manageable safety profile in patients with relapsed/refractory EGFR-mutated NSCLC. Update 2025-05-27. References: 10.1016/j.annonc.2023.09.2352

New Avapritinib, Crenolanib, Midostaurin in Gastrointestinal stromal tumour with KIT D816V: 4

Preclinical studies and case reports. Type II c-Kit inhibitors are resistant to KIT D816 and PDGFR842V mutations. References: 29093181

New Avapritinib, Imatinib, Sunitinib, Regorafenib, Crenolanib, Midostaurin in Gastrointestinal stromal tumour with KIT Exon 11 mutation: 4

Preclinical studies and case reports. References: 29093181

New Crizotinib in Non-small cell lung cancer with MET H1106D, H1094Y, N1100S, R1170Q, M1250T: 4

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Capmatinib in Non-small cell lung cancer with MET V1092I, H1094Y, N1100S, H1106D, R1170Q, L1195V, F1200I, M1250T: 4

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Elzovantinib in Non-small cell lung cancer with MET V1092I, H1094Y, N1100S, H1106D, R1170Q, M1250T: 4

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Tepotinib in Non-small cell lung cancer with MET V1092I, H1094Y, N1100S, H1106D, R1170Q, M1250T: 4

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Cabozantinib in Non-small cell lung cancer with MET V1092I, H1094Y, N1100S, H1106D, R1170Q, Y1230H: 4

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New AG-270 in Solid tumours with MTAP Deletion: 4

Preclinical study. MAT2A inhibitors showed selective growth inhibition in MTAP-deleted cancer cells and tumors, with efficacy correlated to MTAP deletion across >300 cell lines, and induced defects in RNA splicing, leading to antiproliferative effects, with potential for combination strategies with cell cycle or DNA repair inhibitors. References: 10.1158/1538-7445.AM2019-2714

New AG-270 in Solid tumours with MTAP Deletion: 4

Phase 1 trial. NCT03435250. N=40. AG-270/S095033, a MAT2A inhibitor, achieved 2 partial responses and 5 patients with stable disease ≥16 weeks in patients with advanced MTAP-deleted malignancies. References: 39762248

New GSK3368715 in Solid tumours with MTAP Deletion: 4

Preclinical study. GSK3368715, a type I PRMT inhibitor, showed anti-tumor effects and synergy with PRMT5 inhibition, particularly in MTAP-deficient cancer models, suggesting MTAP status as a potential biomarker for patient selection. References: 31257072

New Avapritinib, Crenolanib, Midostaurin in Gastrointestinal stromal tumour with PDGFRA D842V: 4

Preclinical studies and case reports. Type II c-Kit inhibitors are resistant to KIT D816 and PDGFR842V mutations. References: 29093181

New Imatinib, Sunitinib, Regorafenib in Gastrointestinal stromal tumour with KIT D816V: R2

Preclinical studies and case reports. Type II c-Kit inhibitors are sensitive to KIT D816 and PDGFR842V mutations. References: 29093181

New Elzovantinib in Non-small cell lung cancer with MET D1228N, Y1230H: R2

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Tepotinib in Non-small cell lung cancer with MET D1228N, Y1230H: R2

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Crizotinib in Non-small cell lung cancer with MET L1195V, D1228N, Y1230H: R2

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Cabozantinib in Non-small cell lung cancer with MET L1195V, F1200I, M1250T: R2

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Capmatinib in Non-small cell lung cancer with MET Y1230H, D1228N: R2

Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor. References: 38564707

New Cetuximab in Triple-negative breast cancer with NF1 Loss-of-function mutations: R2

Case report. A patient with EGFR-amplified heavily pretreated metastatic triple-negative breast cancer experienced a dramatic response to cetuximab as 7th-line treatment, with disease progression occurring 8 months after treatment initiation, and molecular analysis suggested loss of EGFR phosphorylation and acquisition of an NF1 mutation as potential resistance mechanisms. References: 35100682

New Imatinib, Sunitinib, Regorafenib in Gastrointestinal stromal tumour with PDGFRA D842V: R2

Preclinical studies and case reports. Type II c-Kit inhibitors are sensitive to KIT D816 and PDGFR842V mutations. References: 29093181

New Ponatinib, Vandetanib, Cabozantinib, Ceritinib, Crizotinib, Regorafenib, Sorafenib, Alectinib in Solid tumours with RET I788N: R2

Preclinical study. RET-rearranged tumors. Potent inhibitors AD80 and ponatinib that bind in the DFG-out conformation of RET selectively kill RET-rearranged tumors, while mechanisms of resistance include CCDC6-RET(I788N) mutation and MAPK pathway reactivation. References: 28615362

New Vandetanib, Cabozantinib, Ceritinib, Crizotinib, Regorafenib, Sorafenib, Alectinib in Solid tumours with RET V804M: R2

Preclinical study. RET-rearranged tumors. Potent inhibitors AD80 and ponatinib that bind in the DFG-out conformation of RET selectively kill RET-rearranged tumors, while mechanisms of resistance include CCDC6-RET(I788N) mutation and MAPK pathway reactivation. References: 28615362

Removed GSK2256098 in Meningioma with NF2 alterations Oncogenic mutations: Tier 3

Removed Binimetinib in Melanoma with NRAS alterations Oncogenic mutations: Tier 3

Removed Olaparib in Breast cancer with PALB2 alterations Oncogenic mutations (germline): Tier 3

Removed Belzutifan in Renal cell carcinoma with VHL alterations Oncogenic mutations (germline): Tier 3

Removed Capivasertib + Fulvestrant in Breast cancer with AKT1 alterations E17K: Tier 4

Removed Prexasertib in Colorectal adenocarcinoma with CHEK1 alterations Overexpression: Tier 4

Removed Pexidartinib in Solid tumours with CSF1R alterations Overexpression, Oncogenic mutations: Tier 4

Removed ABBV-637 in Solid tumours with EGFR alterations Amplification: Tier 4

Removed ATR inhibitor in Solid tumours with FANCM alterations S1045, Loss-of-function mutations: Tier 4

Changed Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline): 1

References changed: 34818478, 10.1200/JCO.2021.39.15_suppl.4555, 10.1200/JCO.2020.38.15_suppl.5003.

Changed Ruxolitinib in Polycythemia vera with JAK2 V617F: 1B

Comments changed: Phase 3. NCT01243944. Ruxolitinib demonstrated superiority to standard therapy in patients with polycythemia vera experiencing hydroxyurea inadequacy or intolerance, with significant improvements in hematocrit control (60% vs 20%), spleen volume reduction (38% vs 1%), and symptom management (49% vs 5%).RESPONSE trial.

Changed Vemurafenib in Hairy cell leukaemia with BRAF V600E: 2

Comments changed: Retrospective analysis of 21 HCL patients treated with vemurafenib showed 40% complete remission rate, and median event-free survival of 17 months, with response rate and kinetics independent of dosing.Not TGA approved.

Changed Tagraxofusp-erzs in Blastic plasmacytoid dendritic cell neoplasm with CD123 Overexpression: 2

Comments changed: Phase 1/2 trial. NCT02113982. N=47. Tagraxofusp showed a combined rate of complete response and clinical complete response of 72% in previously untreated BPDCN patients, with an overall response rate of 90% and 45% proceeding to stem-cell transplantation..

Changed Ofatumumab in Chronic lymphocytic leukaemia with CD20 Protein expression: 2

Comments changed: Phase 2 study. N=138. Ofatumumab demonstrated an ORR of 58% in fludarabine- and alemtuzumab-refractory CLL, and 47% in fludarabine-refractory CLL with bulky lymphadenopathy. Median PFS was 5.7-5.9 months, with OS of 13.7-15.4 months..

Changed Tafasitamab + Lenalidomide in Diffuse large B-cell lymphoma with CD19 Overexpression: 3

Comments changed: Phase 2 L-MIND study. NCT02399085. N=81. Tafasitamab plus lenalidomide showed antitumour activity with 60% ORR (43% CR, 18% PR) in patients with relapsed/refractory DLBCL ineligible for autologous stem-cell transplantation..

Changed Crizotinib in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 3

Comments changed: Phase 2/retrospective study. Crizotinib showed antitumor activity in 69 patients with NSCLC harboring MET exon 14 alterations with an ORR of 32%, median DOR of 9.1 months, and median PFS of 7.3 months..

Changed Savolitinib in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 3

Comments changed: Phase 2 study. NCT02897479. Savolitinib showed an IRC-assessed ORR of 49% (30/61) in patients with MET exon 14 skipping pulmonary sarcomatoid carcinoma and other NSCLC subtypes.. References changed: 34166627, 10.1200/JCO.2020.38.15_suppl.951910.1158/1538-7445.AM2019-CT031.

Changed Ibrutinib in Diffuse large B-cell lymphoma, Waldenstroms macroglobulinaemia with MYD88 : 3

Alterations changed: Gain-of-function mutations, L265P, S243N, M232T. Comments changed: Case series. MYD88 mutation analysis in Waldenstorm's macroglobulinemia patients showed that MYD88 mutations (L265P, S243N, and M232T) were associated with response to ibrutinib therapy, with no major responses observed in patients with wild-type MYD88..

Changed GSK2256098 in Meningioma with NF2 Oncogenic mutations: 3

Comments changed: Phase 2 Alliance A071401 trial. NCT02523014. N=36. GSK2256098 showed activity in NF2-mutated meningiomas, meeting PFS6 endpoint with rates of 83% (grade 1) and 33% (grade 2/3), and one partial response was observed. Updated 2024-09-24.Alliance A071401, FAK inhibitor. References changed: 36288512, 10.1200/JCO.2020.38.15_suppl.2502.

Changed Cobimetinib in Histiocytosis with NRAS Oncogenic mutations: 3

Comments changed: Phase 2 proof-of-concept umbrella trial. N=18. Cobimetinib showed an ORR of 89% with durable responses and 94% of patients remaining progression-free at 12 months in patients with histiocytic neoplasms harbouring various MAPK pathway mutations.Phase 2 Umbrella study.

Changed Ribociclib + Binimetinib in Melanoma with NRAS Oncogenic mutations: 3

Comments changed: Phase 1b/2 trial. NCT01781572. N=41 (phase II cohort). Ribociclib + binimetinib showed an ORR of 20% (8/41) and 33% (13/40) in patients with concurrent alterations of CDKN2A, CDK4, or CCND1. Median PFS was 3.7 months and median OS was 11.3 months.. References changed: 35294522, 10.1200/JCO.2017.35.15_suppl.9519.

Changed Olaparib in Breast cancer with PALB2 Oncogenic mutations (germline): 3

References changed: 33119476, 10.1200/JCO.2020.38.15_suppl.1002, 10.1200/JCO.2024.42.16_suppl.1021.

Changed Cisplatin + Gemcitabine in Pancreatic adenocarcinoma with PALB2 Oncogenic mutations (germline): 3

Comments changed: Phase 2 trial. N=50. Cisplatin and gemcitabine in germline BRCA1/2 or PALB2 mutant PDAC demonstrated ORR 65%, DCR 78%, median PFS 9.7 months, and median OS 16.4 months.PFS 10.1mo.

Changed Capivasertib + Paclitaxel in Triple-negative breast cancer with PTEN Loss-of-function mutations: 3

Comments changed: Randomised phase 2 PAKT trial. N=140. Median PFS was 5.9 months with capivasertib plus paclitaxel versus 4.2 months with placebo (HR, 0.74). In patients with PIK3CA/AKT1/PTEN-altered tumors (n = 28), median PFS was 9.3 months versus 3.7 months (HR, 0.30). Median OS was 19.1 months versus 12.6 months (HR, 0.61, NS).PAKT PFS 9.3 v 3.7 mo in PIK3CA/AKT/PTEN altered subgroup. OS/ORR NS.

Changed GSK2636771 in Gastric cancer with PTEN Loss-of-function mutations, loss of protein expression: 3

Comments changed: Phase 1b/2 trial. NCT02615730. In patients with PTEN-deficient advanced gastric cancer, GSK2636771 combined with paclitaxel achieved median PFS of 12.1 weeks and OS of 33.4 weeks. Patients with PTEN-null tumors exhibited superior PFS compared to those with PTEN partial loss tumors..

Changed Cobimetinib in Histiocytosis with RAF1 Oncogenic mutations, K106N: 3

Comments changed: Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations..

Changed Pralsetinib in Solid tumours with RET Fusions: 3

Comments changed: Phase 1/2 ARROW study. NCT03037385. Pralsetinib demonstrated an ORR of 75% in thyroid cancer and 60% in of solid tumours harbouring RET fusions, with durable responses across multiple fusion genotypes..

Changed Tazemetostat in Epithelioid sarcoma with SMARCB1 Oncogenic mutations: 3

Comments changed: Phase 2 basket study. NCT02601950. N=62. Tazemetostat showed clinical activity in patients with advanced epithelioid sarcoma with loss of INI1/SMARCB1, with an ORR of 15%, median PFS of 5.5 months, and median OS of 19.0 months. In Cohort 6 (N=44) Tazemetostat showed an ORR of 11.4% with 1 CR and 4 PR, and 17 patients had SD, resulting in a median PFS of 3.7 months and median OS of 16.6 months.. References changed: 33035459, 10.1200/JCO.2020.38.15_suppl.11564.

Changed Belantamab mafodotin in Multiple myeloma with TNFRSF17 Protein expression: 3

Comments changed: Phase 2 DREAMM-2 study. NCT03525678. N=196. Belantamab mafodotin showed anti-myeloma activity with overall response rates of 31% and 34% in the 2.5 mg/kg and 3.4 mg/kg cohorts respectively in patients with relapsed or refractory multiple myeloma..

Changed Durvalumab + Tremelimumab in Non-small cell lung cancer with Tumour Mutational Burden High: 3

Comments changed: Phase 3 MYSTIC trial. NCT02453282. N=1118. In patients with blood tumor mutational burden ≥20 mutations per megabase, durvalumab plus tremelimumab demonstrated improved OS (21.9 vs 10.0 months). Overall, durvalumab showed no OS improvement over chemotherapy (16.3 vs 12.9 months) in patients with ≥25% PD-L1 tumor cell expression. Similarly, durvalumab plus tremelimumab did not improve OS or PFS compared to chemotherapy..

Changed Capivasertib, Capivasertib + Fulvestrant in Breast cancer with AKT1 E17K: 4

Comments changed: Phase 1. NCT01226316. Capivasertib showed clinical activity as monotherapy (ORR 20%) and in combination with fulvestrant (ORR 36% in fulvestrant-pretreated and 20% in fulvestrant-naive patients) in heavily pretreated AKT1(E17K)-mutant ER-positive metastatic breast cancer patients..

Changed Sapanisertib + Metformin in Solid tumours with AKT1 Oncogenic mutations: 4

Comments changed: Phase 1 trial. NCT03017833. N=30. Sapanisertib + metformin showed anti-tumor activity in patients with mTOR/AKT/PI3K pathway alterations, including 4 patients achieving partial response, 3 of whom had PTEN mutations and 1 had AKT and mTOR mutation..

Changed Sapanisertib + Metformin in Solid tumours with AKT2 Oncogenic mutations: 4

Comments changed: Phase 1 trial. NCT03017833. N=30. Sapanisertib + metformin showed anti-tumor activity in patients with mTOR/AKT/PI3K pathway alterations, including 4 patients achieving partial response, 3 of whom had PTEN mutations and 1 had AKT and mTOR mutation..

Changed Alectinib in Solid tumours with ALK EML4-ALK fusion, F1174L, R1275Q, L1196M, C1156Y: 4

Comments changed: Preclinical study. CH5424802 (Alectinib), a potent and selective ALK inhibitor, showed antitumor activity against ALK-driven cancers, including NSCLC and ALCL, and inhibited the resistant gatekeeper mutant ALK L1196M..

Changed Alectinib in Neuroblastoma with ALK F1245C: 4

Comments changed: Case report. Refractory metastatic neuroblastoma harboring an ALK F1245C mutation achieved a partial response with alectinib monotherapy, with significant symptom improvement and reduction in tumor size. Resistance eventually developed after 16 weeks..

Changed Therapy in Non-small cell lung cancer with ALK Fusion, T1151M, T1151_L1152insT, L1152R, L1152P, C1156Y, I1171N, F1174L, F1174S, F1174C, V1180L, L1196M and L1198F, L1198F and C1156Y, L1198F, G1202R and L1198F, G1202R, G1202del, D1203N, D1203N and E1210K, S1206R, E1210K and S1206C, E1210K, L1196M, F1245C, G1269A, S1269S, R1275Q: 4

Therapy changed: ZotizalkibTPX-0131. Comments changed: Cell line assays comparing Zotizalkib against approved ALK inhibitorsCell line assays comparing TPX-0131 against approved ALK inhibitors.

Changed LY3214996 in Solid tumours with BRAF Oncogenic mutations: 4

Comments changed: Phase 1. NCT02857270. LY3214996, an ERK1/2 inhibitor, showed acceptable safety profile, favorable PK, and potent tumor PD inhibition in patients with advanced cancer, with tumor regression observed in 7 patients and stable disease in 4 patients.. References changed: 31744895, 10.1200/JCO.2019.37.15_suppl.300123614898, 10.1158/1538-7445.AM2017-4973, 10.1200/JCO.2019.37.15_suppl.3001.

Changed Therapy in Solid tumours with BRAF Oncogenic mutations: 4

Therapy changed: LY3214996, LY3214996 + AbemaciclibSCH772984. Comments changed: Preclinical study. LY3214996, a novel ERK1/2 inhibitor, demonstrated potent anti-tumor activity in cancer models with MAPK pathway alterations, including BRAF, NRAS, or KRAS mutations, and showed enhanced efficacy in combination with CDK4/6 inhibitor abemaciclib.. References changed: 10.1158/1538-7445.AM2017-497323614898.

Changed Therapy in Solid tumours with BRAF Oncogenic mutations: 4

Therapy changed: SCH772984Trametinib, MEK inhibitor. Comments changed: Preclinical study. ERK inhibitor SCH772984 displayed nanomolar cellular potency in tumor cells with BRAF, NRAS, or KRAS mutations and induced tumor regressions in xenograft models, including those resistant to BRAF and MEK inhibitors.. References changed: 2361489830770389.

Changed Dabrafenib + Trametinib in Colorectal neuroendocrine carcinoma with BRAF V600E: 4

Comments changed: Two case reports of high-grade rectal NEC with durable response to combined BRAF and MEK inhibition with DOR of 7 and 9 months respectively.Two case reports of hHigh-grade rectal NEC with durable response to combined BRAF and MEK inhibition with DOR of 7 and 9 months respectively..

Changed PLX8394 in Solid tumours with BRAF V600E: 4

Comments changed: Preclinical study. RAF inhibitor PLX8394 disrupts BRAF dimers and selectively inhibits ERK signaling in tumors driven by dimeric BRAF mutants and BRAF V600 monomers..

Changed SHP099 + Trametinib in Solid tumours with BRAF V600E: 4

Comments changed: Preclinical study. SHP2 inhibition combined with ERK signaling inhibition prevents adaptive resistance in ERK-dependent tumors with specific molecular profiles, such as TNBC and RAS G12 mutations, but not in those with RAS G13D, RAS Q61X, or certain BRAF V600E mutations..

Changed Exarafenib in Solid tumour with BRAF V600E, Class II mutations, Class III mutations: 4

Comments changed: Phase 1/1b trial. NCT04913285. Exarafenib demonstrated promising clinical activity and tolerability in patients with BRAF-altered solid tumors and NRAS mutant melanoma, with a ORR 18% and SD in 47% of patients..

Changed Ulixertinib in Low-grade gliomas with BRAF V600E, KIAA1549-BRAF fusion, Fusion: 4

Comments changed: Preclinical study. Ulixertinib showed activity in pediatric low-grade glioma models with MAPK pathway alterations..

Changed Cobimetinib in Melanoma with BRAF V600E, V600K: 4

Comments changed: Preclinical study. Cobimetinib demonstrates efficacy in both KRAS-driven and BRAF-mutant tumours, reflecting the distinct mechanisms of action among MEK inhibitors..

Changed Lifirafenib in Melanoma with BRAF V600E, V600K: 4

Comments changed: Phase 1 trial. N=131. Lifirafenib showed antitumor activity in patients with B-RAF(V600)-mutated solid tumors, including melanoma, thyroid cancer, and LGSOC, as well as K-RAS-mutated NSCLC and endometrial carcinoma..

Changed Lifirafenib in Solid tumours with BRAF V600E, V600K: 4

Comments changed: Phase 1 trial. N=131. Lifirafenib showed antitumor activity in patients with B-RAF(V600)-mutated solid tumors, including melanoma, thyroid cancer, and LGSOC, as well as K-RAS-mutated NSCLC and endometrial carcinoma..

Changed Encorafenib + Osimertinib in Non-small cell lung cancerEGFR:exon 19 deletion and BRAF:V600E: 4

Biomarker changed: BRAF+EGFR. Comments changed: Preclinical study. Acquired BRAF V600E mutation identified as a resistant mechanism to osimertinib treatment in a patient with T790M, with cells showing sensitivity to BRAF V600E inhibitor and enhanced vulnerability to combination treatment with osimertinib. Updated 2025-05-27Cell line study. Combining osimertinib with a BRAF V600E inhibitor had a significant inhibitory effect in a patient derived cell line model..

Changed Oxaliplatin, Cisplatin in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 4

Comments changed: Retrospective analysis of patients with advanced pancreatic ductal adenocarcinoma showed improved OS (21.8 vs 8.1 months) in those with germline BRCA1, BRCA2, or PALB2 mutations, particularly when treated with platinum-based chemotherapy (1-year OS: 94% vs 60%)..

Changed Olaparib + Ceralasertib in Triple-negative breast cancer with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 4

Comments changed: Phase 2 plasmaMatch Cohort E. ISRCTN16945804. N=70. Olaparib + ceralasertib in TNBC patients without targetable mutation showed a ORR of 17% and median PFS of 4.3 months, not meeting pre-specified efficacy criteria. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS..

Changed Oxaliplatin, Cisplatin in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 4

Comments changed: Retrospective analysis. N=29. Patients with advanced PDAC and germline BRCA1, BRCA2, or PALB2 mutations demonstrate improved overall survival (21.8 months vs 8.1 months in controls) and enhanced benefit from platinum-based chemotherapy (1-year OS 94% vs 60%)..

Changed Olaparib in Uterine leiomyosarcoma with BRCA2+PTEN BRCA2:deletion and PTEN:deletion: 4

Comments changed: Case report. A patient with metastatic uterine leiomyosarcoma harboring BRCA2, TP53, and PTEN deletions showed rapid response to olaparib after progressing on multiple prior treatments including gemcitabine-docetaxel, doxorubicin, and temozolomide..

Changed Ribociclib in Solid tumours with CCND1 Amplification: 4

Comments changed: Phase 1 study. N=132. Ribociclib demonstrated preliminary signs of clinical activity with 3 partial responses and 8 patients progression-free for >6 months..

Changed Dinaciclib + MK2206 in Ovarian cancer with CCNE1 Amplification: 4

Comments changed: Preclinical study. Cyclin E1 (CCNE1) amplification in high-grade serous ovarian cancer is selectively targeted by combined inhibition of CDK2 and AKT, showing synergistic effects and potential to overcome resistance.High grade ovarian cancer.

Changed Adavosertib in Triple-negative breast cancer with CCNE1 Amplification: 4

Comments changed: Preclinical study. Cyclin E overexpression sensitizes triple-negative breast cancer to Wee1 kinase inhibition by AZD1775, suggesting its potential as a biomarker for monotherapy in cyclin E-high tumors and sequential combination therapy in cyclin E-low tumors..

Changed Cisplatin, Veliparib in Ovarian cancer with CDK12 Loss of protein expression: 4

Comments changed: Preclinical study. Ovarian cancer-associated CDK12 mutations impair its catalytic activity, disrupt homologous recombination repair, and sensitize cells to cisplatin and PARP inhibitors by reducing BRCA1 levels.Pre-clinical only.

Changed Anti-PD-1 monoclonal antibody in Prostate cancer with CDK12 Loss of protein expression: 4

Comments changed: Integrative genomic analysis of 360 metastatic castration-resistant prostate cancer samples. The subtype with biallelic loss of CDK12 is characterized by focal tandem duplications, increased gene fusions, and elevated neoantigen burden, potentially benefiting from immune checkpoint immunotherapy..

Changed SR-4835 in Triple-negative breast cancer with CDK12 Protein expression: 4

Comments changed: Preclinical study. SR-4835, a dual CDK12/CDK13 inhibitor, disables triple-negative breast cancer cells by triggering intronic polyadenylation site cleavage, suppressing DNA damage response proteins, and promoting synergy with DNA-damaging chemotherapy and PARP inhibitors..

Changed Palbociclib in Glioblastoma with CDKN2A Loss of protein expression: 4

Comments changed: Preclinical study. GBM cell lines and tumors. Co-deletion of CDKN2A predicts sensitivity to CDK4/6 inhibition, identifying a subset of GBMs likely to respond to targeted therapy.Cell line study.

Changed Palbociclib in Non-small cell lung cancer with CDKN2A Oncogenic mutations: 4

Comments changed: Phase 2 TAPUR study. NCT02693535. N=28 (NSCLC with CDKN2A loss or mutation). Palbociclib monotherapy showed anti-tumor activity with a ORR of 3.6% and disease control rate of 29% (1 PR, 6 SD at 16 weeks), median PFS 7.9 weeks, and median OS 20.6 weeks.TAPUR. N=28. 1 PR. 6 SD.

Changed Therapy in Solid tumours with CDKN2A+MTAP CDKN2A:deletion and MTAP:deletion: 4

Therapy changed: EPZ015666PRMT inhibitor,type 1. Comments changed: Preclinical study. MTAP-deficient cancer cells, frequently resulting from CDKN2A deletion, accumulate MTA, inhibiting PRMT5, and rendering them dependent on PRMT5, suggesting PRMT5 inhibitors as a potential therapy for MTAP/CDKN2A-deleted tumors.. References changed: 26912361, 27068473, 31257072, 10.1158/1538-7445.AM2019-2714.

Changed Tusamitamab ravtansine in Non-small cell lung cancer with CEACAM5 Overexpression: 4

Comments changed: Phase1/2 trial. NCT02187848. SAR408701, an antibody-drug conjugate, showed promising antitumor activity in heavily pretreated NSQ NSCLC patients with high CEACAM5 expression, with an ORR of 20%..

Changed Berzosertib + PF-477736 in Small-cell lung cancer with CHEK1 Overexpression: 4

Comments changed: Preclinical study. Significant overexpression of CHEK1 and CDC25A/B/C genes in SCLC. ATR and CHK1 inhibitors induce genotoxic damage and apoptosis in SCLC cell lines, but not in lung adenocarcinoma cells, indicating SCLC's dependence on ATR/CHK1-mediated cell cycle checkpoints.Pre-clinical only.

Changed AMB-05X in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 4

Comments changed: Phase 2 trial. N=8. Intra-articular administration of AMB-05X, a CSF1R antibody, yielded high and sustained local concentrations with low systemic exposures, resulting in significant pharmacodynamic effects in tenosynovial giant cell tumor patients..

Changed Tarloxotinib in Non-small cell lung cancer with EGFR A763insFQEA, V769insASV, D770insSVD, H773insNPH: 4

Comments changed: Preclinical study. Tarloxotinib-E showed efficacy against Ba/F3 cells with various EGFR exon 20 mutations, with identified acquired resistance mechanisms being T790M or C797S secondary mutations depending on the original EGFR exon 20 mutation.Cell line study..

Changed Afatinib in Cervical cancer with EGFR Amplification: 4

Comments changed: Case report. A 52-year-old patient with EGFR-amplified metastatic cervical squamous cell carcinoma benefited from afatinib with a PFS of 5.5 months and achieved partial response, and subsequently achieved stable disease with everolimus and afatinib at disease progression..

Changed Cetuximab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with EGFR Amplification: 4

Comments changed: Phase 2 study (N=7) of anti-EGFR treatment in EGFR-amplified gastroesophageal adenocarcinoma patients demonstrated ORR of 58% (including 1 CR), DCR of 100%, and median PFS of 10 months. Resistance mechanisms were identified through NGS and ctDNA analysis.1CR 1PR but small sample size.

Changed Cetuximab with EGFR Amplification: 4

Cancer type(s) changed: Breast cancer, Triple-negative breast cancer Comments changed: Case report. A patient with EGFR-amplified heavily pretreated metastatic triple-negative breast cancer experienced a dramatic response to cetuximab as 7th-line treatment, with disease progression occurring 8 months after treatment initiation, and molecular analysis suggested loss of EGFR phosphorylation and acquisition of an NF1 mutation as potential resistance mechanisms.Case report. Triple-Negative Breast Cancer. References changed: 3510068210.1200/PO.18.00310.

Changed Gefitinib in Non-small cell lung cancer with EGFR Amplification and NOT Oncogenic mutation: 4

Comments changed: Case report. Lung adenocarcinoma, wild-type EGFR, and EGFR gene amplification showed complete remission after treatment with gefitinib, suggesting EGFR gene amplification as a potential biomarker for predicting response to EGFR-TKIs in patients with advanced NSCLC.Case report of wild-type amplified EGFR.

Changed Afatinib in Non-small cell lung cancer with EGFR E709_T710delinsD: 4

Comments changed: Case report. A lung adenocarcinoma patient with rare EGFR E709_T710delinsD mutation achieved 23 months progression-free survival when treated with afatinib as first-line therapy, and subsequent almonertinib treatment resulted in stable disease.Case report. Partial response to afatinib with clinical benefit of 23 months..

Changed Afatinib in Non-small cell lung cancer with EGFR E709_T710delinsD: 4

Comments changed: Case report. Stage IV lung adenocarcinoma harboring the rare EGFR exon 18 E709_T710delinsD mutation showed significant clinical and radiographic response to treatment with afatinib.Case report. Both CT and metabolic response to afatinib..

Changed Gefitinib in Non-small cell lung cancer with EGFR E709_T710delinsD: 4

Comments changed: Case report. Stage IV NSCLC harboring the rare EGFR delE709_T710insD mutation achieved a partial response to erlotinib, with a 47% reduction in tumor size..

Changed Erlotinib in Non-small cell lung cancer with EGFR EGFR-RAD51 fusion: 4

Comments changed: Preclinical and case series study. EGFR gene fusions, most commonly EGFR-RAD51, were identified in lung cancer and found to be oncogenic and targetable with EGFR tyrosine kinase inhibitors (TKI) and therapeutic antibodies, with documented antitumor responses in four patients treated with EGFR TKI..

Changed Erlotinib in Non-small cell lung cancer with EGFR EGFR-RAD51 Fusion, EGFR-PURB fusion: 4

Comments changed: Case report. Stage IV NSCLC harbouring EGFR-RAD51 fusion experienced a remarkable tumour response to erlotinib, suggesting that NSCLC patients with EGFR-RAD51 fusion may respond to treatment with EGFR inhibitors.. References changed: 29290255, 27413714, 27102076.

Changed Erlotinib in Colorectal adenocarcinoma with EGFR EGFR-SEPT14 Fusion: 4

Comments changed: Case report. Colorectal adenocarcinoma harboring a rare EGFR-SEPT14 fusion achieved a partial response to erlotinib, an EGFR tyrosine kinase inhibitor, before developing resistance with the emergence of EGFRvIII mutation..

Changed Erlotinib, Gefitinib, Afatinib, Osimertinib in Non-small cell lung cancer with EGFR Exon 18 deletion, Exon 18 mutation, E709_T710delinsD, E709K, G719A: 4

Comments changed: Preclinical study. Lung cancer cells with EGFR exon 18 mutations (G719A, E709K, Del18) showed higher sensitivity to afatinib and neratinib compared to 1st and 3rd generation TKIs, indicating potential effective treatment options for patients with these mutations.OncoKB LOE 3. Cell line study. In Ba/F3 cells transfected with exon 18 deletion or mutations, Afatinb demonstrated higher relative sensitivity (IC90) than Gefitinib, Erlotinib, as well as third-generation TKIs Osimertinib and CO1686..

Changed Tarloxotinib in Non-small cell lung cancer with EGFR Exon 19 deletion and L718V, Exon 19 deletion and G724S, Exon 19 deletion and L792F, Exon 19 deletion and L792H, Exon 19 deletion and C797S, L858R and L718Q, L858R and L718V, L858R and L792F, L858R and L792H, L858R and C797G: 4

Comments changed: Preclinical study. Tarloxotinib-E showed activity against Ba/F3 cells with various EGFR exon 20 mutations, with identified acquired resistance mechanisms being T790M or C797S secondary mutations, influenced by the original EGFR exon 20 mutation.Cell line study..

Changed Afatinib in Non-small cell lung cancer with EGFR Exon 19 deletion and L718V, Exon 19 deletion and G724S, Exon 19 deletion and L792F, Exon 19 deletion and L792H, Exon 19 deletion and C797S, L858R and L718Q, L858R and L718V, L858R and L792F, L858R and L792H, L858R and C797G, L858R and C797S: 4

Comments changed: Preclinical study. Afatinib showed activities against Ba/F3 cells with various EGFR exon 20 mutationsCell line study..

Changed Afatinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, G719A, G719S, S768I, L861R, L861Q, A763_Y764insFQEA: 4

Comments changed: Preclinical study. Mobocertinib (TAK-788) demonstrated potent inhibition of EGFR exon 20 insertion mutants in non-small cell lung cancer with selectivity over wild-type EGFR..

Changed Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861R, L861Q, A763_Y764insFQEA, P772_H773insGNP, A767_V769dup: 4

Comments changed: Preclinical study. Mobocertinib (TAK-788) demonstrated potent inhibition of EGFR exon 20 insertion mutants in non-small cell lung cancer with selectivity over wild-type EGFR..

Changed Afatinib in Non-small cell lung cancer with EGFR G724S and R776H: 4

Comments changed: Case report. A novel KIF5B-EGFR fusion identified in lung adenocarcinoma demonstrated remarkable response to Afatinib treatment..

Changed Afatinib + Bevacizumab in Non-small cell lung cancer with EGFR KIF5B-EGFR fusion: 4

Comments changed: Case report. A novel KIF5B-EGFR fusion was identified in lung adenocarcinoma, and the patient showed a response to EGFR tyrosine kinase inhibitors (TKIs)..

Changed Afatinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

Comments changed: Case report. Afatinib achieved disease control in a Chinese patient with lung adenocarcinoma harboring rare EGFR exon 18-25 kinase domain duplication..

Changed Afatinib, Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

Comments changed: EGFR kinase domain duplication (EGFR-KDD) is a rare oncogenic driver in NSCLC, identified in 0.12% of patients, with 85% having the canonical exon 18-25 duplication, and shows partial response to targeted therapies, notably afatinib, in some patients.OncoKB LOE 3.

Changed Therapy with EZH2 Oncogenic mutations, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687V: 4

Therapy changed: GSK126Tazemetostat. Cancer type(s) changed: Diffuse large B-cell lymphomaSolid tumours Comments changed: Preclinical study. EZH2 inhibition by GSK126 decreases global H3K27me3 levels, reactivates silenced PRC2 target genes, and inhibits proliferation of EZH2 mutant DLBCL cell lines and xenografts..

Changed Tazemetostat in Non-Hodgkin’s lymphoma with EZH2 Oncogenic mutations, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687V: 4

Comments changed: Preclinical study. EPZ-6438, a potent EZH2 inhibitor, showed antitumor activity in EZH2-mutant non-Hodgkin lymphoma models, with dose-dependent tumor growth inhibition and sustained tumor regressions, confirming EZH2 dependency in these cancers..

Changed Fisogatinib in Hepatocellular carcinoma with FGF19 Overexpression: 4

Comments changed: Preclinical and clinical study. Fisogatinib, a potent FGFR4 inhibitor, showed clinical activity in HCC patients with aberrant FGF19 expression, but resistance emerged with gatekeeper and hinge-1 mutations in FGFR4 kinase domain..

Changed Everolimus in Breast cancer with FGFR1 Amplification: 4

Comments changed: Preclinical and clinical study. FGFR1 amplification is associated with endocrine resistance but retained sensitivity to mTOR inhibitor everolimus in hormone receptor-positive metastatic breast cancer, suggesting a potential therapeutic role for mTOR inhibitors in ER+, FGFR1+ metastatic breast cancer..

Changed Avapritinib in Gastrointestinal stromal tumour with KIT Oncogenic mutations, Exon 11 mutation, Exon 9 mutation, D816E, D816F, D816I, D816V, D816Y, V560G, V559D, D820E, Y823D, D820Y, D557

Tier changed: 43. Comments changed: Preclinical studies and case reports. BLU-285 Responses seen in KIT D820Y mutation treated with showed a 25% tumor shrinkage, and a patient with advanced SM treated with BLU-285 showed a marked decrease in bone marrow mast cells, indicating early antitumor activity.Not TGA approved.

Changed Therapy in Solid tumours with MET Alterations: 4

Therapy changed: ElzovantinibTPX-0022.

Changed Vismodegib in Medulloblastoma with PTCH1 Oncogenic mutations

Tier changed: 43. Comments changed: Case report. A 26-year-old man with metastatic medulloblastoma refractory to multiple therapies showed rapid, transient tumor regression and symptom reduction after treatment with GDC-0449 with molecular analysis indicating hedgehog pathway activation and PTCH1 mutation..

Changed Everolimus in Breast cancer with PTEN Loss-of-function mutations

Tier changed: 43. Comments changed: Exploratory biomarker analysis of BOLERO-1 and BOLERO-3 trials. Everolimus associated with improved PFS in patients with PIK3CA mutations (HR, 0.67), PTEN loss (HR, 0.54), or hyperactive PI3K pathway (HR, 0.67)..

Changed Trametinib in Histiocytosis with RAF1 Oncogenic mutations: 4

Comments changed: Preclinical study and case reports. Whole-exome and transcriptome sequencing identified diverse and targetable kinase alterations, including recurrent kinase fusions and mutations, in BRAF(V600E)-wild-type non-Langerhans cell histiocytosis. Treatment with MEK and RAF inhibitors showed response in patients with MAP2K1- and ARAF-mutated non-LCH..

Changed Ponatinib in Solid tumours with RET : 4

Alterations changed: KIF5B-RET fusion, CCDC6-REF fusion, V804MI788N. Comments changed: Preclinical study. RET-rearranged tumors. Potent inhibitors AD80 and ponatinib that bind in the DFG-out conformation of RET selectively kill RET-rearranged tumors, while mechanisms of resistance include CCDC6-RET(I788N) mutation and MAPK pathway reactivation..

Changed Vandetanib in Medullary thyroid cancer with RET M918T: 4

Comments changed: Phase 3 ZETA trial. Post hoc analysis. Vandetanib showed significant improvement in PFS (HR, 0.43) in patients with progressive and symptomatic medullary thyroid cancer, with ORR of 37% versus 2% in placebo arm.. References changed: 32584630, 32083997.

Changed Vistusertib in Gastric cancer with RICTOR Amplification: 4

Comments changed: Preclinical study. RICTOR amplification identified in 2% of 640 patients with metastatic solid tumors, prevalent in 3.8% of gastric cancer, and a RICTOR-amplified patient-derived cell line showed sensitivity to AZD2014-mediated mTORC1/2 inhibition..

Changed Wnt-C59 in Solid tumours with RNF43 Oncogenic mutations: 4

Comments changed: Preclinical study. Porcupine inhibitor C59 strongly inhibited growth of Rnf43;Znrf3-mutant intestinal neoplasia by suppressing paracrine Wnt-driven growth, while sparing adjacent normal crypts..

Changed Crizotinib in Non-small cell lung cancer with ALK G1269S: R2

Comments changed: Cell line assays comparing Zotizalkib against approved ALK inhibitorsCell line assays comparing TPX-0131 against approved ALK inhibitors.

Changed Alectinib in Non-small cell lung cancer with ALK I1171N, G1202R, G1202del: R2

Comments changed: Cell line assays comparing Zotizalkib against approved ALK inhibitorsCell line assays comparing TPX-0131 against approved ALK inhibitors.

Changed Crizotinib in Non-small cell lung cancer with ALK L1196M and L1198F, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A: R2

Comments changed: Cell line assays comparing Zotizalkib against approved ALK inhibitorsCell line assays comparing TPX-0131 against approved ALK inhibitors.

Changed Alectinib, Brigatinib, Ceritinib, Lorlatinib in Non-small cell lung cancer with ALK L1196M and L1198F, L1198F and C1156Y, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A: R2

Comments changed: Cell line assays comparing Zotizalkib against approved ALK inhibitorsCell line assays comparing TPX-0131 against approved ALK inhibitors.

Changed Ceritinib in Non-small cell lung cancer with ALK L1198F, G1202R: R2

Comments changed: Cell line assays comparing Zotizalkib against approved ALK inhibitorsCell line assays comparing TPX-0131 against approved ALK inhibitors.

Changed Serclutamab Talirine in Solid tumours with EGFR Amplification

Tier changed: R24. Comments changed: Phase 1 study. NCT03234712. Serclutamab talirine, an anti-EGFR antibody-drug conjugate, showed a tolerable safety profile but minimal antitumor activity in 24 patients with glioblastoma, with 1 partial response lasting ~33 months and 6 stable disease. Updated 2025-05-27.. References changed: 36814898NCT03234712.

Changed Erlotinib in Colorectal adenocarcinoma with EGFR

Alterations changed: vIIIEGFR-SEPT14 Fusion. Tier changed: R24. Comments changed: Case report. Colorectal adenocarcinoma harboring a rare EGFR-SEPT14 fusion achieved a partial response to erlotinib, an EGFR tyrosine kinase inhibitor, before developing resistance with the emergence of EGFRvIII mutation. Updated 2025-05-27.

Changed Trastuzumab in Gastric cancer with PIK3CA N345T, H1047R, H1047L: R2

Comments changed: Case-control study. AMNESIA. Patients with HER2-positive metastatic gastric cancer and no alterations in the AMNESIA panel (EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications) had significantly longer median PFS (5.2 vs 2.6 months) and OS (16.1 vs 7.6 months)..

Changed Pictilisib + Fulvestrant in Breast cancer with PIK3CA Oncogenic mutations: R2

Comments changed: Phase 2 FERGI trial. NCT01437566. Pictilisib + fulvestrant did not improve PFS over placebo + fulvestrant in oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer patients with or without PIK3CA mutations.FERGI. PIK3CA mutation status had no effect on benefit..

Changed Taselisib in Lung squamous cell carcinoma with PIK3CA Oncogenic mutations: R2

Comments changed: Phase 2 Lung-MAP S1400B trial. NCT02785913. Taselisib showed limited efficacy with 5% response rate (1/21) in patients with PIK3CA-altered squamous NSCLC, with median PFS 2.9 months and OS 5.9 months.Lung-MAP S1400B, ORR 5%.

Changed Osimertinib in Non-small cell lung cancer with PIK3CA Oncogenic mutations: R2

Comments changed: Biomarker analysis. Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy, including off-target mechanism..

Changed Lapatinib in Glioblastoma with PTEN Loss of protein expression: R2

Comments changed: Phase 1/2 trial of lapatinib in recurrent glioblastoma multiforme; PTEN loss was seen in 6 out of 16 patients, but no correlation was observed with outcome and PTEN status. ORR 0%.Phase 1/2 trial. Lapatinib. Recurrent GBM. ORR 0%..

Changed GSK2636771 in Solid tumours with PTEN Loss-of-function mutations, loss of protein expression: R2

Comments changed: Phase 2 NCI-MATCH trial. NCT02465060. Modest activity observed with GSK2636771 in patients with PTEN mutation/deletion or protein loss, with 1 partial response (4.5%) and 9 stable diseases (32% and 37.5% in Arms N and P respectively) in 56 treated patients.NCI-MATCH Below expected response rate.

Changed RMC-4550 in Solid tumours with PTPN11 E76K: R2

Comments changed: Preclinical study. RMC-4550, a potent SHP2 allosteric inhibitor, showed efficacy in cancer models with PTPN11 mutation-associated drivers, including class 3 BRAF mutants, NF1 loss, and KRASG12C, by disrupting SOS1-mediated RAS-GTP loading, resulting in tumour growth inhibition and regressions in vivo.Cell line study..

Changed SHP099 in Solid tumours with PTPN11 P491Q: R2

Comments changed: Preclinical study. SHP2 inhibition by SHP099 prevents adaptive resistance to MEK inhibitors in multiple cancer models by impeding SOS/RAS/MEK/ERK1/2 reactivation and blocking ERK1/2-dependent transcriptional programs.Cell line data.

Changed RMC-4550 in Solid tumours with RAC1 P29S: R2

Comments changed: Preclinical study. Cell line study SHP2 phosphatase inhibition by RMC-4550 disrupts SOS1-mediated RAS-GTP loading, decreasing oncogenic RAS/RAF/MEK/ERK signalling in cancers driven by RAS-GTP-dependent oncogenic BRAF, NF1 loss, and nucleotide-cycling oncogenic KRAS."Cell line study..

Changed Vemurafenib, PLX8394 in Low-grade gliomas with RAF1 Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion: R2

Comments changed: Preclinical study. CRAF gene fusions in pediatric low-grade gliomas are unresponsive to RAF inhibitors due to robust protein-protein interactions mediated by the N-terminal non-kinase fusion partner, but are sensitive to pan-RAF dimer inhibitor LY3009120 and combinatorial inhibition of MAPK/mTOR pathway.Paediatric low-grade gliomas.

Changed RMC-4550 in Solid tumours with RAF1 P261L: R2

Comments changed: Cell line study. Preclinical study. SHP2 phosphatase inhibition with RMC-4550 disrupts SOS1-mediated RAS-GTP loading, decreasing oncogenic RAS/RAF/MEK/ERK signalling and cancer growth in human cancer models with RAS-GTP-dependent oncogenic BRAF, NF1 loss, or nucleotide-cycling oncogenic KRAS..

Changed Vemurafenib + Cobimetinib in Langerhans cell sarcoma with RASA1 Loss-of-function mutations: R2

Comments changed: Case report. RASA1 loss identified as a mechanism of resistance to BRAF inhibitor in a BRAF V600-mutated Langerhans cell sarcoma patient..

Changed Palbociclib, Ribociclib, Abemaciclib in Breast cancer, Solid Tumours with RB1 Loss-of-function mutations: R2

Comments changed: Phase 3 PALOMA-3 trial analysis. Acquired mutations in ESR1 (notably Y537S) and PIK3CA emerged as resistance mechanisms to palbociclib plus fulvestrant, with RB1 mutations also emerging in a minority of patients (4.7%) on the palbociclib arm..

Changed Osimertinib in Non-small cell lung cancer with RET Fusion: R2

Comments changed: Biomarker analysis. 155 EGFR-mutant lung cancer patients revealed EGFR T790M mutation (63%) as the most common mechanism of acquired resistance to EGFR-TKI therapy, followed by MET amplification (5%), HER2 amplification (13%), small cell transformation (3%), and other off-target mechanism including RET fusion..

Changed Crizotinib in Non-small cell lung cancer with ROS1+MET ROS1:fusion AND MET:D1228N: R2

Comments changed: Case report. A patient with metastatic lung adenocarcinoma with CD74-ROS1 fusion developed resistance to crizotinib through an acquired MET D1228N mutation and showed short-term disease control with cabozantinib..

Changed Patritumab deruxtecan in Non-small cell lung cancer with TOP1 L721R: R2

Comments changed: Phase 1 U31402-A-U102 trial. N=102/78 (safety/efficacy). Patritumab deruxtecan (HER3-DXd) showed cORR of 41% and median OS of 16.2 months in EGFR-mutated NSCLC after EGFR TKI and platinum-based chemotherapy, with acquired mutations in ERBB3 and TOP1 potentially conferring resistance to HER3-Dxd..

Monday, 26 May 2025 (Version: 20250526AU)

New Trastuzumab deruxtecan in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and ERBB2:Protein expression and NOT ERBB2:amplification, ESR1:Protein expression and ERBB2:Low protein expression and NOT ERBB2:amplification, ESR1:Protein expression and ERBB2:Ultra-low protein expression: 1

TGA approved. FDA approved. Phase 3 DESTINY-Breast06 trial. NCT04494425. N=866. Trastuzumab deruxtecan significantly improved PFS over chemotherapy (13.2 versus 8.1 months) in patients with hormone receptor-positive, HER2-low metastatic breast cancer who had received endocrine-based therapy. HER2 status is defined by Ventana's Pathway anti-HER-2 (4B5) Rabbit Monoclonal Primary Antibody. HER2-ultralow is IHC 0 with membrane staining, and HER2-low is IHC 1+ or IHC 2+/ISH-negative. References: 39282896

New Nivolumab + Ipilimumab in Colorectal adenocarcinoma with Microsatellite Instability High: 1B

TGA approved. Not PBS reimbursed. FDA approved. Phase 3 CheckMate 8HW trial. NCT04008030. Nivolumab plus ipilimumab significantly improved PFS over chemotherapy (24-month PFS 72% vs 14%) in patients with MSI-H or dMMR metastatic colorectal cancer who had not previously received systemic treatment for metastatic disease. References: 39602630

New Nivolumab + Ipilimumab in Colorectal adenocarcinoma with Mismatch repair Deficient: 1B

TGA approved. Not PBS reimbursed. FDA approved. Phase 3 CheckMate 8HW trial. NCT04008030. Nivolumab plus ipilimumab significantly improved PFS over chemotherapy (24-month PFS 72% vs 14%) in patients with MSI-H or dMMR metastatic colorectal cancer who had not previously received systemic treatment for metastatic disease. References: 39602630

New Vimseltinib in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 2

FDA approved. Phase 3 MOTION trial. NCT05059262. N=123. Vimseltinib achieved a significant objective response rate of 40% compared to 0% with placebo (p<0.0001) in patients with tenosynovial giant cell tumour. Note that alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1. References: 38843860

New Avutometinib + Defactinib in Low-grade serous ovarian cancer with KRAS Oncogenic mutation: 2

FDA granted accelerated approval to avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer based on RAMP-201 trial (NCT04625270, N=57) results showing an ORR of 44% and DOR range of 3.3-31.1 months. Publication pending. References: 10.1200/JCO.2023.41.16_suppl.5515, NCT04625270

New Telisotuzumab Vedotin in Non-small cell lung cancer with MET Overexpression: 2

Not TGA approved. FDA approved (accelerated). Phase 2 LUMINOSITY trial. NCT03539536. N=172. Telisotuzumab vedotin showed an ORR of 28.6% in patients with c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, with a median DoR of 8.3 months and median OS of 14.5 months. ORR in c-Met high subgroup (≥50% of tumor cells with 3+ by SP44) was 35% (n=78) vs 23% Intermediate (25-50% of tumor cells with 3+, n=83). References: 38843488

New Mirdametinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 2

FDA approved. Phase 2b ReNeu trial. NCT03962543. N=114 (58 adults, 56 children). Mirdametinib showed confirmed ORR of 41% in adults and 52% in children with NF1-associated plexiform neurofibromatosis. Median target PN volumetric best response of -41% and -42% respectively, and improvement in pain and health-related quality of life. References: 39514826

New Sunitinib in Thymic carcinoma with KIT Oncogenic mutations: 4

Retrospective analysis of French RYTHMIC network database. N=28. Sunitinib in previously-treated thymic epithelial tumors with disease control rate 63%, ORR 22%, median PFS 3.7 months, and median OS 15.4 months. Among 8 sequenced patients, 1 PR and 2 PD observed, exon 11 c-Kit mutation and achieved PFS 5.5 months and OS 7.5 months. References: 27237035

New MOMA-341 in Solid tumours with Microsatellite Instability High: 4

Preclinical study. MOMA-341, a novel WRN inhibitor, showed antitumor activity in MSI-H models in preclinical studies. Direct measurement of TA repeat expansions by long-read sequencing outperformed MSI-H status as a predictor of sensitivity, enabling near-perfect prediction of MOMA-341 anti-tumor activity. References: 10.1158/1538-7445.AM2025-4205

Removed Erlotinib; Gefitinib in Non-small cell lung cancer with EGFR alterations C797S, C797G: Tier 3

Changed Pembrolizumab + Trastuzumab + Cisplatin + Fluorouracil, Pembrolizumab + Trastuzumab + Capecitabine + Oxaliplatin in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification

Tier changed: 1B2. Comments changed: TGA approved. Not PBS reimbursed. FDA approved 5/5/2021. Phase 3: KEYNOTE-811 (NCT03615326). First interim analysis. ORR 74% for pembro + SOC vs 52% for SOC alone. DOR 10.6 vs 9.5mo.Not TGA approved. FDA approved 5/5/2021. Phase 3: KEYNOTE-811 (NCT03615326). First interim analysis. ORR 74% for pembro + SOC vs 52% for SOC alone. DOR 10.6 vs 9.5mo..

Changed Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF V600E: 2

Comments changed: Not TGA approved. FDA approved. Phase 3 BREAKWATER trial. NCT04607421. Encorafenib + cetuximab + mFOLFOX6 significantly improved ORR over SOC (60.9% vs 40.0%) in previously untreated BRAF V600E-mutant metastatic colorectal cancer, with a median duration of response of 13.9 months versus 11.1 months..

Changed Zorifertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 3

Comments changed: Phase 1, BLOOM study. NCT02228369. N=67..

Changed Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR Exon 19 insertion: 3

Comments changed: Retrospective analysis of NSCLC patients. Both EGFR exon 19 insertion and A763_Y764 insFQEA showed sensitivity to EGFR TKIs, with response rates of 56% and 73%, and median time to progression of 10.4 months and 5.0 months, respectively..

Changed Pembrolizumab + Trastuzumab + Oxaliplatin + Capecitabine in Gastroesophageal junction adenocarcinoma, Gastric Cancer with ERBB2 Amplification, Overexpression: 3

Comments changed: Phase 2 trial. NCT02954536. N=37. Pembrolizumab + trastuzumab + chemotherapy achieved primary endpoint of 6-month PFS in 70% (26/37) of HER2-positive metastatic oesophagogastric cancer patients..

Changed Neratinib in Breast cancer with ERBB2 ERBB2:Oncogenic mutations and NOT ERBB2:amplification: 3

Comments changed: Phase 1/2 SUMMIT trial. NCT01953926. Neratinib showed activity in breast cancer (n=​25), ORR at week 8 was 32%..

Changed Trastuzumab deruxtecan in Non-small cell lung cancer with ERBB2 Kinase domain mutation: 3

Comments changed: Phase 2 DESTINY-Lung01 trial. NCT03505710. N=42. Trastuzumab deruxtecan showed a confirmed ORR of 62% with median DOR not reached and estimated median PFS of 14.0 months in patients with HER2-mutated NSCLC, with 91% having prior platinum-based chemotherapy..

Changed Pyrotinib in Non-small cell lung cancer with ERBB2 Oncogenic mutations, A775_G776insYVMA (Y772_A775dup), exon 20 insertion: 3

Comments changed: Phase 2 trial. NCT02535507. Pyrotinib showed significant antitumor activity against HER2 exon 20-mutated NSCLC in patient-derived organoids and xenografts, with a 53% ORR and 6.4 months median PFS in 15 patients..

Changed Afatinib, Dacomitinib, Pyrotinib, Poziotinib in Non-small cell lung cancer with ERBB2 P780_Y781insGSP (G778_P780dup): 3

Comments changed: Preclinical study. Structural modeling and molecular dynamics simulations revealed that HER2 ex20ins mutants with shorter alphaC-beta4 loop, such as G778_P780dup, had higher affinity to TKIs like afatinib and sustained tumor responses were observed in patients treated with these inhibitors..

Changed Fulvestrant + Neratinib in Breast cancer with ERBB2 S310F, S310Y, L755S, A775_G776insYVMA (Y772_A775dup), V777L, P780_Y781insGSP (G778_P780dup), L869R: 3

Comments changed: Phase 2 SUMMIT trial. NCT01953926. N=81. Neratinib showed activity in HER2-mutant metastatic breast cancer with ORR of 17.4% and 36.4% in ER+ and ER- patients on monotherapy, and 29.8% in ER+ patients on combination with fulvestrant; median PFS was 3.6, 2.0, and 5.4 months respectively..

Changed Infigratinib in Urothelial carcinoma with FGFR3 Fusions, FGFR3-TACC3 fusion, Oncogenic mutations, R248C, S249C, Y375C, Y373C, G370C, F386L, K650E: 3

Comments changed: Phase 1/2 trial. N=67. BGJ398 showed an ORR of 25% and DCR of 64% in patients with advanced urothelial carcinoma with FGFR3 alterations, with a median PFS of 3.8 months and median OS of 7.8 months..

Changed Bevacizumab + erlotinib in Papillary renal cell carcinoma with FH Loss-of-function mutations (germline): 3

Comments changed: Phase 2 study. NCT01130519. N=83. Bevacizumab + Erlotinib showed an ORR of 51% (HLRCC cohort: 64%, sporadic cohort: 37%) and median PFS of 14.2 months (HLRCC cohort: 21.1 months, sporadic cohort: 8.7 months) in advanced papillary renal cell carcinoma..

Changed Pazopanib in Gastrointestinal stromal tumour with KIT Oncogenic mutations: 3

Comments changed: Phase 2 PAZOGIST trial. NCT01323400. Pazopanib plus best supportive care improved PFS (HR 0.59) with 4-month PFS 45% versus 18% in best supportive care alone in imatinib and sunitinib-resistant advanced gastrointestinal stromal tumours.NCCN 2A.

Changed Neratinib in Solid tumours with ERBB2 Kinase domain mutation, S310, exon 20 insertion

Tier changed: 43. Comments changed: Phase 1/2 SUMMIT trial. NCT01953926. Neratinib showed activity in Her2 S310, Kinase domain hotspot, and some exon 20 insertion hotspot mutations.

Changed Imatinib, Sunitinib in Thymic carcinoma with KIT Oncogenic mutations

Tier changed: 43. Comments changed: Case report. A patient with c-kit mutation-positive thymic carcinoma achieved long-term disease control (~27 months) with consecutive treatment of imatinib and sunitinib, demonstrating the efficacy of molecular-targeted therapy for thymic carcinoma with oncogenic driver mutations.OncoKB LOE 2; Strong case report; Sunitinib standard of care; NCCN 2A. References changed: 27073655, 27237035.

Changed Neratinib in Non-small cell lung cancer with ERBB2 Oncogenic mutations, A775_G776insYVMA (Y772_A775dup), exon 20 insertion

Tier changed: R24. Comments changed: Phase 1/2 SUMMIT trial. NCT01953926. Multi-histology, genomically selected basket trial of neratinib. Only 1 (of 26) responder was seen in non-small cell lung cancer.Single responders in lung ca..

Changed Neratinib in Solid tumours with ERBB3 Oncogenic mutations, R103G, V104L, V104M, G284R, D297Y, T355A, E928G: R2

Comments changed: Phase 1/2 SUMMIT trial. NCT01953926. Multi-histology, genomically selected basket trial. No response to Neratinib were seen in patients with ERBB3 hotspot mutations.SUMMIT. No response seen in patients with ERBB3 hotspot mutations..

Sunday, 25 May 2025 (Version: 20250525AU)

Saturday, 24 May 2025 (Version: 20250524AU)

New Zongertinib in Non-small cell lung cancer with ERBB2 Tyrosine kinase domain mutation, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, L755P, G776V: 3

Phase 1a/b trial. NCT04886804. Zongertinib demonstrated clinical benefit in HER2-mutant NSCLC patients, with objective response rates of 71% (120mg dose), 48% (Cohort 5), and 30% (Cohort 3), and a median PFS of 12.4 months. References:

New Osimertinib + Gefitinib in Non-small cell lung cancer with EGFR C797S and T790M: 4

Case report. Combination osimertinib and gefitinib in a NSCLC patient with EGFR C797S and T790M mutations in trans demonstrated brief clinical improvement with rapid decline in C797S mutation subclone, but the patient ultimately died from progressive disease 6 weeks after starting therapy. References: 28843359

New Zongertinib in Non-small cell lung cancer with ERBB2 Extracellular domain mutation, Transmembrane domain, Intracellular domain, S310F, S310Y, D277Y, S113F, V659E, G660D, P1199S: 4

Phase 1a/b trial. NCT04886804. Zongertinib demonstrated clinical benefit in HER2-mutant NSCLC patients, with objective response rates of 71% (120mg dose), 48% (Cohort 5), and 30% (Cohort 3), and a median PFS of 12.4 months. References:

New RMC-6236 in Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal adenocarcinoma with KRAS G12, G12D, G12V, G12C, G12A, G12S: 4

Preclinical study. RMC-6236, a RAS(ON) multi-selective noncovalent inhibitor, demonstrated anticancer activity across RAS-addicted cell lines and induced tumor regressions in KRASG12X xenograft models. In a phase I/Ib clinical trial (NCT05379985), the inhibitor showed initial activity with objective responses in patients with advanced KRASG12X lung and pancreatic adenocarcinoma. References: 38593348

Removed Olaparib in Pancreatic adenocarcinoma with BRCA2 alterations Oncogenic mutations (germline): Tier 2

Removed Erdafitinib in Urothelial carcinoma with FGFR3 alterations Fusion, Oncogenic mutations: Tier 2

Changed Brigatinib in Non-small cell lung cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: TGA approved. PBS reimbursed. FDA approved. Phase 3 ALTA-1L trial. NCT02737501. N=275. Brigatinib demonstrated superior PFS (24.0 vs 11.0 months) and improved health-related quality of life in ALK inhibitor-naive ALK-positive non-small cell lung cancer patients, with consistent results across independent and investigator assessments.TGA approved. PBS reimbursed; FDA approved.

Changed Olaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations (germline): 1

Comments changed: TGA approved. PBS reimbursed. Phase 3 SOLO2/ENGOT-Ov21 trial. NCT01874353. N=295. Olaparib maintenance therapy significantly improved PFS (19.1 vs 5.5 months) and provided a clinically meaningful OS benefit (51.7 vs 38.8 months) in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation.TGA approved. PBS reimbursed. SOLO2 trial..

Changed Olaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations (germline): 1

Comments changed: TGA approved. PBS reimbursed. Phase 3 SOLO2/ENGOT-Ov21 trial. NCT01874353. N=295. Olaparib maintenance therapy significantly improved PFS (19.1 vs 5.5 months) and provided a clinically meaningful OS benefit (51.7 vs 38.8 months) in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation.TGA approved. PBS reimbursed. SOLO2 trial..

Changed Gefitinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 1

Comments changed: PBS reimbursed. Phase 3 trials. NCT00322452 and C000000376. Gefitinib significantly improved PFS (10.8 vs 5.4 months, HR 0.30) and ORR (73.7% vs 30.7%) compared to carboplatin-paclitaxel in patients with advanced NSCLC with sensitising EGFR mutations..

Changed Afatinib in Non-small cell lung cancer with EGFR G719, L861Q, S768I: 1

Comments changed: PBS reimbursed. Phase 3 LUX-Lung 6 trial. NCT01121393. N=364. Afatinib significantly improved PFS (11.0 months vs 5.6 months) compared to gemcitabine and cisplatin in Asian patients with EGFR mutation-positive advanced NSCLC.PBS reimbursed. LUX-Lung 6.

Changed Docetaxel + Trastuzumab in Breast cancer with ERBB2 Amplification, Overexpression: 1

Comments changed: PBS reimbursed if ISH positive. Trastuzumab + docetaxel significantly improved ORR (61% vs 34%), OS (31.2 vs 22.7 months), and PFS (11.7 vs 6.1 months) over docetaxel alone in HER2-positive metastatic breast cancer patients with manageable additional toxicity..

Changed Fulvestrant in Breast cancer with ESR1 Protein expression: 1

Comments changed: TGA approved. PBS reimbursed. Phase 3 FALCON trial. NCT01602380. N=462. Fulvestrant significantly improved PFS over anastrozole (HR 0.797, 16.6 months vs 13.8 months) in endocrine therapy-naive patients with hormone receptor-positive advanced breast cancer..

Changed Abemaciclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: TGA approved. PBS reimbursed. Phase 3 MONARCH 2 trial. NCT02107703. N=669. Abemaciclib + fulvestrant significantly improved PFS (16.4 vs 9.3 months) and ORR (48.1% vs 21.3%) compared to placebo + fulvestrant in HR+/HER2- advanced breast cancer patients who progressed on endocrine therapy.TGA approved. PBS reimbursed. MONARCH-2.

Changed Palbociclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: TGA approved. PBS reimbursed. Phase 3 PALOMA-3 trial. NCT01942135. N=521. Fulvestrant plus palbociclib significantly improved progression-free survival (9.5 vs 4.6 months) in hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy, across PIK3CA mutational status and hormone-receptor expression levels.TGA approved. PBS reimbursed. PALOMA-3.

Changed Ribociclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: TGA approved. PBS reimbursed. Phase 3 MONALEESA-3 trial. NCT02422615. N=726. Ribociclib plus fulvestrant significantly improved PFS (20.5 months vs 12.8 months) over placebo plus fulvestrant in hormone receptor-positive, HER2-negative advanced breast cancer patients, with consistent effects in treatment-naive and pretreated patients. This combination also showed a significant overall survival benefit (HR, 0.72) with an estimated overall survival at 42 months of 57.8% versus 45.9%.TGA approved. PBS reimbursed. MONALEESA-3. References changed: 29860922, 3182636029860922, 27908454, 31826360.

Changed Sacituzumab Govitecan in Triple-negative breast cancer with ESR1+ERBB2 NOT ESR1:protein expression and NOT ERBB2:amplified: 1

Comments changed: TGA approved; Not PBS reimbursed. FDA approved. Phase 3 ASCENT trial (NCT02574455, N=468): Sacituzumab govitecan significantly improved PFS (5.6 vs 1.7 months) and OS (12.1 vs 6.7 months) over single-agent chemotherapy in metastatic triple-negative breast cancer, with an ORR of 35%.TGA approved; Not PBS reimbursed. FDA approved. Anti Trop-2 ADC. Phase 1/2: ORR 33%. Median DOR 7.7 months. CBR 45%. Median PFS: 5.5 months. Phase 3 ASCENT trial: OS: 12.1 vs 6.7 months (chemotherapy)..

Changed FOLFIRI + Cetuximab in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Comments changed: TGA approved. FDA approved. Phase 3 trial. CRYSTAL. NCT00154102. N=1198. Cetuximab + FOLFIRI reduced risk of progression of metastatic colorectal cancer compared to FOLFIRI alone (HR 0.85), with significant benefit in patients with wild-type KRAS tumors (HR 0.68).TGA approved. FDA approved. CRYSTAL.

Changed Dostarlimab in Endometrial cancer with Microsatellite Instability High: 1

Comments changed: FDA approved 09/02/2023. GARNET trial (NCT02715284, Phase 1, N=104): Dostarlimab showed an ORR of 42.3% (30/71) in dMMR/MSI-H endometrial cancer as assessed by IHC, PCR or NGS, with 12.7% CR and 29.6% PR. Median DOR not reached, with 96.4% and 76.8% of responses sustained at 6 and 12 months respectively.GARNET trial: dMMR as assessed by IHC or MSI-H by PCR or NGS. ORR 43% with 13% CR. Duration of response at 6 months: 96%. FDA approved 09/02/2023..

Changed Imatinib in Dermatofibrosarcoma protuberans with PDGFB COL1A1-PDGFB Fusion: 1

Comments changed: TGA approved. PBS reimbursed. Imatinib demonstrates activity against dermatofibrosarcoma protuberans characterised by the COL1A1-PDGFB fusion gene..

Changed Dabrafenib + Trametinib in Anaplastic thyroid cancer with BRAF V600E: 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 2 trial. N=16. Dabrafenib + Trametinib showed a confirmed ORR of 69% in patients with BRAF V600E-mutated anaplastic thyroid cancer, with 12-month estimates of DOR, PFS, and OS being 90%, 79%, and 80% respectively..

Changed Trametinib in Melanoma with BRAF V600E, V600K: 1B

Comments changed: TGA approved. PBS reimbursement must include concomitant dabrafenib. Phase 3 trial. NCT01245062. N=322. Trametinib improved PFS (4.8 months vs 1.5 months) and OS (81% vs 67% at 6 months) compared to chemotherapy in patients with BRAF V600E or V600K mutated metastatic melanoma. Single agent NOT recommended.TGA approved. PBS reimbursement must include concomitant dabrafenib. Single agent NOT recommended..

Changed Olaparib in Breast cancer with BRCA1 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3 OlympiAD trial. NCT02000622. N=302. Olaparib monotherapy significantly improved PFS (7.0 vs 4.2 months) and ORR (59.9% vs 28.8%) compared to standard therapy in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation.TGA approved. Not PBS reimbursed. OlympiAd..

Changed Talazoparib in Breast cancer with BRCA1 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3 EMBRACA trial. NCT01945775. N=431. Talazoparib significantly improved PFS (8.6 vs 5.6 months) and ORR (62.6% vs 27.2%) over standard single-agent therapy in patients with advanced breast cancer and germline BRCA1/2 mutation.TGA approved. Not PBS reimbursed. EMBRACA trial..

Changed Olaparib in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Phase 3 POLO trial. NCT02184195. N=154. Olaparib maintenance therapy did not show a statistically significant OS benefit (19.0 vs 19.2 months) versus placebo in germline BRCA-mutated metastatic pancreatic cancer, but showed a clinically meaningful benefit in time to first subsequent cancer therapy or death (HR, 0.44) and long-term survival in a subset of patients.TGA approved. POLO trial..

Changed Olaparib in Breast cancer with BRCA2 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3 OlympiAD trial. NCT02000622. N=302. Olaparib monotherapy significantly improved PFS (7.0 vs 4.2 months) and ORR (59.9% vs 28.8%) compared to standard therapy in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation.TGA approved. Not PBS reimbursed. OlympiAd..

Changed Talazoparib in Breast cancer with BRCA2 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 3 EMBRACA trial. NCT01945775. N=431. Talazoparib significantly improved PFS (8.6 vs 5.6 months) and ORR (62.6% vs 27.2%) over standard single-agent therapy in patients with advanced breast cancer and germline BRCA1/2 mutation.TGA approved. Not PBS reimbursed. EMBRACA trial..

Changed Olaparib in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Phase 3 POLO trial. NCT02184195. N=154. Olaparib maintenance therapy did not show a statistically significant OS benefit (19.0 vs 19.2 months) versus placebo in germline BRCA-mutated metastatic pancreatic cancer, but showed a clinically meaningful benefit in time to first subsequent cancer therapy or death (HR, 0.44) and long-term survival in a subset of patients.TGA approved. POLO trial..

Changed Lu-177 vipivotide tetraxetan in Prostate cancer with PSMA Protein expression

Tier changed: 1B2. Comments changed: TGA approaved. FDA approved 2022-03-24. Phase 3 VISION trial. NCT03511664. N=831. Lutetium-177-PSMA-617 plus standard care significantly prolonged PFS (8.7 vs 3.4 months, HR 0.40) and OS (15.3 vs 11.3 months, HR 0.62) in patients with PSMA-positive (Gallium-68 positive) metastatic castration-resistant prostate cancer.FDA approved 2022-03-24. Phase 3. VISION. N=831. PSMA-positive metastatic lesion defined as Gallium-68 positive. Median OS: 15.3 v 11.3 months (HR: 0.62). Radiological PFS: HR 0.40. 8.7 v 3.4 months..

Changed Ensartinib in Non-small cell lung cancer with ALK Fusion: 2

Comments changed: Not TGA approved. TGA approved. Phase 3 trial. eXalt3. NCT02767804. Ensartinib showed superior efficacy to crizotinib with significantly longer median PFS (25.8 vs 12.7 months) in the first-line metastatic setting and higher intracranial response rate (63.6% vs 21.1%) in patients with ALK-positive NSCLC.Phase 3. eXalt3. Median PFS of Ensartinib was 25.8 months versus 12.7 months (Crizotinib) in the first-line metastatic setting..

Changed Crizotinib in Inflammatory myofibroblastic tumour with ALK Fusions, RANBP2-ALK Fusion: 2

Comments changed: Not TGA approved. FDA approved 14/7/2022. Sustained partial response observed in a patient with ALK-translocated inflammatory myofibroblastic tumor (IMT) treated with crizotinib, whereas no activity was seen in a patient without ALK translocation..

Changed Atezolizumab + Cobimetinib + Vemurafenib in Melanoma with BRAF V600E: 2

Comments changed: Not TGA approved. Phase 3 IMspire150 trial. NCT02908672. N=514. Atezolizumab + vemurafenib + cobimetinib significantly improved PFS (15.1 vs 10.6 months; HR 0.78) compared to placebo + vemurafenib + cobimetinib in BRAF(V600) mutation-positive advanced melanoma patients..

Changed Veliparib + Carboplatin + Paclitaxel in Triple-negative breast cancer with BRCA1 Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. Phase 3 BROCADE3 trial. NCT02163694. N=509. Median PFS was significantly longer in patients receiving veliparib with carboplatin-paclitaxel versus placebo (14.5 months vs 12.6 months) with a HR of 0.71 in patients with germline BRCA mutation-associated advanced HER2-negative breast cancer..

Changed Veliparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. Phase 3 trial. VELIA/GOG-3005. NCT02470585. N=1140. Veliparib added to carboplatin and paclitaxel induction therapy followed by veliparib maintenance significantly improved PFS in BRCA-mutation cohort (34.7 vs 22.0 months), HRD cohort (31.9 vs 20.5 months), and intention-to-treat population (23.5 vs 17.3 months)..

Changed Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations, Oncogenic mutations (germline), M1V, M1I, C61G, C64Y, R71G, R71K, R1495M, E1559K, D1692N, D1692H, R1699W, A1708E, G1788V: 2

Comments changed: Not TGA approved. Phase 3 ARIEL3 trial. NCT01968213. N=564. Rucaparib maintenance treatment significantly improved PFS in patients with platinum-sensitive ovarian cancer, with median PFS of 16.6 months vs 5.4 months in BRCA-mutant carcinoma, 13.6 months vs 5.4 months in homologous recombination deficient carcinoma, and 10.8 months vs 5.4 months in the intention-to-treat population. Both germline and somatic BRCA1/2 mutations are included.Not TGA approved. ARIEL3. Both g/tBRCA.

Changed Veliparib + Carboplatin + Paclitaxel in Triple-negative breast cancer with BRCA2 Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. Phase 3 BROCADE3 trial. NCT02163694. N=509. Median PFS was significantly longer in patients receiving veliparib with carboplatin-paclitaxel versus placebo (14.5 months vs 12.6 months) with a HR of 0.71 in patients with germline BRCA mutation-associated advanced HER2-negative breast cancer..

Changed Veliparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. Phase 3 trial. VELIA/GOG-3005. NCT02470585. N=1140. Veliparib added to carboplatin and paclitaxel induction therapy followed by veliparib maintenance significantly improved PFS in BRCA-mutation cohort (34.7 vs 22.0 months), HRD cohort (31.9 vs 20.5 months), and intention-to-treat population (23.5 vs 17.3 months)..

Changed Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations, Oncogenic mutations (germline), M1R, M1I, V159M, V211L, V211I, R2336P, R2336H: 2

Comments changed: Not TGA approved. Phase 3 ARIEL3 trial. NCT01968213. N=564. Rucaparib maintenance treatment significantly improved PFS in patients with platinum-sensitive ovarian cancer, with median PFS of 16.6 months vs 5.4 months in BRCA-mutant carcinoma, 13.6 months vs 5.4 months in homologous recombination deficient carcinoma, and 10.8 months vs 5.4 months in the intention-to-treat population. Both germline and somatic BRCA1/2 mutations are included.Not TGA approved. ARIEL3. Both g/tBRCA.

Changed Pyrotinib + Capecitabine in Breast cancer with ERBB2 Amplification: 2

Comments changed: Not TGA approved. Phase 3 PHOEBE trial. NCT03080805. N=267. Pyrotinib plus capecitabine significantly improved PFS (12.5 months vs 6.8 months, HR 0.39) compared to lapatinib plus capecitabine in HER2-positive metastatic breast cancer patients previously treated with trastuzumab and taxanes.Not TGA approved; PHOEBE. References changed: 33581774, 10.1200/JCO.2020.38.15_suppl.1003.

Changed Trastuzumab deruxtecan in Non-small cell lung cancer with ERBB2 : 2

Alterations changed: S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA (Y772_A775dup), A775_G776insTVMA, G776S, G776delinsVC, V777L, P780_Y781insGSP (G778_P780dup), G778_S779insLPS, Exon 20 insertion, Exon 20 mutationS310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, P780_Y781insGSP, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation.

Changed Erdafitinib in Urothelial carcinoma with FGFR2 Fusions, FGFR2-BICC1 fusion, FGFR2-CASP7 fusion: 2

Comments changed: Not TGA approved. FDA approved. Phase 2. BLC2001. NCT02365597. Erdafitinib showed an objective response rate of 40% (3% complete response, 37% partial response) in previously treated patients with locally advanced or metastatic urothelial carcinoma with FGFR alterations, with median PFS of 5.5 months and OS of 13.8 months.Not TGA approved; FDA approved.

Changed Erdafitinib in Urothelial carcinoma with FGFR3 Fusions, FGFR3-TACC3 fusion, FGFR3-BAIAP2L1 fusion, R248C, S249C, G370C, Y373C: 2

Comments changed: Not TGA approved. FDA approved. Phase 2. BLC2001. NCT02365597. Erdafitinib showed an objective response rate of 40% (3% complete response, 37% partial response) in previously treated patients with locally advanced or metastatic urothelial carcinoma with FGFR alterations, with median PFS of 5.5 months and OS of 13.8 months.Not TGA approved; FDA approved.

Changed Erdafitinib in Urothelial carcinoma with FGFR3 S249C, Y373C, R248C, G370C, Fusion, FGFR1-TACC3:fusion, FGFR1-TACC3:fusion_V1, FGFR1-TACC3:fusion_V3, FGFR3-BAIAP2L1 fusion: 2

References changed: 37870920, 10.1200/JCO.2023.41.17_suppl.LBA4619.

Changed Cobimetinib, Trametinib in Histiocytosis with MAP2K1 P142L, P124Q, Q56P, P105_107del: 2

Comments changed: Phase 1/2 proof-of-concept trial. N=18. Cobimetinib showed an ORR of 89% in patients with histiocytic neoplasms, with durable responses and 94% of patients remaining progression-free at one year, regardless of genotype and presence of various MAPK-pathway mutations.Phase 2 Umbrella study.

Changed Cobimetinib in Histiocytosis with MAP2K2 Oncogenic mutations, Y134H: 2

Comments changed: Phase 1/2 proof-of-concept trial. N=18. Cobimetinib showed an ORR of 89% in patients with histiocytic neoplasms, with durable responses and 94% of patients remaining progression-free at one year, regardless of genotype and presence of various MAPK-pathway mutations.Phase 2 trial.

Changed Dasatinib in Gastrointestinal stromal tumour with PDGFRA D842V, Exon 18 mutation: 2

Comments changed: Not TGA approved. Phase 2 single-arm trial. N=50. Dasatinib showed 6-month PFS rate of 29% and objective response in 25% of patients with imatinib-resistant GISTs, with a higher 6-month PFS rate of 50% in a subset of patients with pSRC expression.Not TGA approved; NCCN 2A.

Changed Avapritinib in Gastrointestinal stromal tumour with PDGFRA Exon 18 mutation, D842V, D842_H845del: 2

Comments changed: Not TGA approved; FDA approved. Phase 1 NAVIGATOR trial. NCT02508532. Avapritinib showed promising antitumor activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumors, with an overall response rate of 88% (5 complete responses, 44 partial responses). In the first-line setting at 300 mg (RP2D), ORR was 93% (26/28) with a CBR of 100%.Not TGA approved; FDA approved. NAVIGATOR trial; First-line. At 300 mg (RP2D). ORR was 93% (26/28) and CBR was 100%..

Changed Pimitespib in Gastrointestinal stromal tumour with PDGFRA Oncogenic mutations: 2

Comments changed: Phase 3. CHAPTER-GIST-301. Phase 3 CHAPTER-GIST-301 trial. N=86. Pimitespib significantly improved PFS (2.8 months vs 1.4 months) and cross-over-adjusted OS (13.8 vs 9.6 months) compared with placebo in patients with advanced GIST refractory to standard TKIs. Single-agent Pimitespib was effective in treat-refractory GIST patients after imatinib, sunitinib, and regorafenib failure, including those with secondary KIT resistance.Phase 3. CHAPTER-GIST-301. Single-agent Pimitespib in treat-refractory GIST patients after imatinib, sunitinib, and regorafenib failure. Median PFS was 2.8 vs. 1.4 mo (placebo). Median OS: 13.8 vs 9.6 mo (placebo). Pimitespib was also effective in patients who had secondary KIT resistance.. References changed: 35688358, 10.1200/JCO.2021.39.15_suppl.11524.

Changed Pralsetinib in Non-small cell lung cancer with RET Fusions, CCDC6-RET fusion, KIF5B-RET fusion: 2

Comments changed: Not TGA approved. FDA approved. Phase 1/2 ARROW trial (NCT03037385, N=233) demonstrated pralsetinib efficacy with ORR 61% (53/87) and DCR 91% (79/87) in RET fusion-positive NSCLC patients previously treated with platinum-based chemotherapy, and 70% ORR in 27 treatment-naive patients.Not TGA approved. FDA approved. ARROW. ORR 61% (53/87) with DCR 91% (79/87) in previous platinum group..

Changed Selpercatinib in Thyroid cancer with RET Fusions, CCDC6-RET fusion, NCOA4-RET fusion, CCDC186-RET fusion, ERC1-RET fusion, KTN1-RET fusion, RUFY3-RET fusion: 2

Comments changed: Not TGA approved. FDA Approved. Phase 1/2 LIBRETTO-001 trial. NCT03157128. Selpercatinib showed durable efficacy with ORR of 69%, 73%, and 79% in RET-altered thyroid cancer patients, including those with prior vandetanib/cabozantinib treatment, treatment-naive, and RET fusion-positive thyroid cancer, respectively.Not TGA approved. FDA Approved. LIBRETTO-001.

Changed 177Lu-DOTA-radioconjugate in Pancreatic neuroendocrine tumour, Neuroendocrine tumour with SSTR2 Protein expression: 2

Comments changed: Not TGA approved; FDA approved; Phase 3 NETTER-1 trial. NCT01578239. N=229. (177)Lu-Dotatate significantly improved PFS (65.2% vs 10.8% at 20 months) and ORR (18% vs 3%) compared to high-dose octreotide LAR in patients with advanced midgut neuroendocrine tumors..

Changed Capivasertib + Paclitaxel in Triple-negative breast cancer with AKT1 E17K: 3

Comments changed: Randomised phase 2 PAKT trial. N=140. Capivasertib + paclitaxel showed longer PFS (5.9 vs 4.2 months, NS) and OS (19.1 vs 12.6 months, NS) over placebo + paclitaxel in metastatic triple-negative breast cancer, with more pronounced magnitude (but non-significant) in patients with PIK3CA/AKT1/PTEN-altered tumors (PFS: 9.3 vs 3.7 months).PAKT PFS 9.3 v 3.7 mo in PIK3CA/AKT/PTEN altered subgroup. OS/ORR NS.

Changed Ipatasertib + Paclitaxel in Triple-negative breast cancer with AKT1 E17K: 3

Comments changed: Phase 2 LOTUS trial. NCT02162719. N=124. Ipatasertib + paclitaxel improved PFS over placebo + paclitaxel (6.2 vs 4.9 months) in metastatic triple-negative breast cancer, with more pronounced effect in PTEN-low population (6.2 vs 3.7 months, NS).LOTUS trial – Ipatasertib + Taxol in TNBC.

Changed Ensartinib in Non-small cell lung cancer with ALK EML4-ALK Fusion, Fusions: 3

Comments changed: Phase 2 trial. NCT03215693. Ensartinib showed an ORR of 52% in crizotinib-resistant, ALK-positive NSCLC patients, with 70% intracranial ORR in patients with measurable brain metastases, and was generally well-tolerated with mostly grade 1 or 2 treatment-related adverse events..

Changed Crizotinib in Solid tumours with ALK Fusion: 3

Comments changed: Phase 2 NCI-MATCH (EAY131) Subprotocol F. NCT02465060. Crizotinib showed a response rate of 50% (1 complete response) in 4 eligible patients with ALK rearrangements and 25% in patients with ROS1 rearrangements, with median PFS of 3.8 and 4.3 months, and median OS of 4.3 and 6.2 months, respectively.NCI-MATCH (EAY131) Subprotocol F. N=4 with ORR of 50%..

Changed Crizotinib in Neuroblastoma with ALK R1275Q: 3

Comments changed: Phase 2 study. ADVL0912. While crizotinib showed limited activity with an ORR of 15% in patients with relapsed/refractory ALK-positive neuroblastoma, with responses seen in patients with ALK Arg1275Gln mutation."Phase 2 study. ADVL0912. ORR 15%.

Changed Nirogacestat in Aggressive fibromatosis with APC Loss-of-function mutations; oncogenic mutations: 3

Comments changed: Phase 2. N=17. PF-03084014, a gamma-secretase inhibitor, showed clinical activity in patients with desmoid tumors, with confirmed partial responses in evaluable patients who remained on study for over 2 years. A total of 15 patients had APC or CTNNB1 mutations. ORR was 29% (5/17), and 5/17 had stable disease. Neither APC loss-of-function nor CTNNB1 gain-of-function mutations was selected prospectively, but these are known central alterations in aggressive fibromatosis. Responses were observed regardless of mutation status.N=17. A total of 15 patients had APC or CTNNB1 mutations. ORR was 29% (5/17), and 5/17 had stable disease. Neither APC loss-of-function or CTNNB1 gain-of-function mutations was selected prospectively, but are known central alteration in aggressive fibromatosis. Responses were seen regardless of APC or CTNNB1 mutations..

Changed Bicalutamide in Salivary gland cancers with AR Protein expression: 3

Comments changed: Phase 2 trial. AR-positive salivary gland carcinoma. CAB (leuprorelin acetate + bicalutamide) showed an ORR of 41.7% and CBR of 75.0%, with median PFS of 8.8 months and median OS of 30.5 months.UMIN000005703. References changed: 28208703, 29211833.

Changed Enzalutamide in Triple-negative breast cancer with AR Protein expression: 3

Comments changed: Phase 2 trial. NCT01889238. Enzalutamide demonstrated clinical activity with a CBR at 16 weeks of 25% in the ITT population and 33% in the evaluable subgroup, and was well tolerated in patients with advanced AR-positive TNBC.. References changed: 29373071, 10.1200/jco.2015.33.15_suppl.1003.

Changed Enobosarm in Breast cancer with AR+ESR1 AR:Protein expression and ESR1:Protein expression: 3

Comments changed: Phase 2 trial. NCT02463032. N=136. Enobosarm in postmenopausal women with AR-positive, ER-positive, HER2-negative advanced breast cancer demonstrated clinical benefit rates of 32% (9mg cohort) and 29% (18mg cohort) at 24 weeks. AR positivity was defined by IHC positive cell percentage, with nuclei staining percentage correlating with ORR and CBR.AR positivity is defined as percentage of IHC positive cells. Postmenopausal women ER positive. CBR at 24 weeks. 32% in 9mg cohort. 29% in 18mg cohort. % nuclei staining correlates with ORR and CBR.. References changed: 38342115, 10.1200/JCO.2021.39.15_suppl.1020.

Changed Vemurafenib + Cobimetinib in Colorectal adenocarcinoma with BRAF V600: 3

Comments changed: Phase 2 TAPUR trial. NCT not specified. N=30. Cobimetinib plus vemurafenib showed antitumor activity in CRC patients with BRAF mutations, with disease control rate of 52% and ORR of 30%, rejecting the null hypothesis of 15% disease control rate (P < .0001). Median duration of therapy was 8.1 weeks. Median PFS was 15.7 weeks.TAPUR Phase 2 Basket trial. The ORR was 30%, and the DCR was 52%. Median duration of therapy was 8.1 weeks. Median PFS was 15.7 weeks..

Changed Panitumumab + Dabrafenib + Trametinib in Colorectal adenocarcinoma with BRAF V600E: 3

Comments changed: Phase 1/2 trial evaluating combined BRAF, EGFR, and MEK inhibition in 142 patients with BRAF(V600E)-mutant colorectal cancer, showing confirmed response rates of 10% for dabrafenib + panitumumab, 21% for dabrafenib + trametinib + panitumumab, and 0% for trametinib + panitumumab..

Changed Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600E: 3

Comments changed: Phase 1/2 study. NCT02124772. N=139. Trametinib monotherapy and combination with dabrafenib showed clinical efficacy in pediatric BRAF V600-mutant low-grade glioma with ORR of 15% and 25% respectively, and manageable safety.. References changed: 36375115, 10.1200/JCO.2020.38.15_suppl.10506.

Changed Vemurafenib + Cobimetinib in Papillary craniopharyngioma with BRAF V600E: 3

Comments changed: Phase 2 Alliance A071601. NCT03224767. N=16. BRAF-MEK inhibitor combination vemurafenib-cobimetinib showed 94% objective response rate (15 of 16 patients) with 91% median reduction in tumor volume in patients with BRAF-mutated papillary craniopharyngiomas.Phase 2 Alliance A071601. NCT03224767. Objective response in 15 of 16 patients.. References changed: 37437144, 10.1200/JCO.2021.39.15_suppl.2000.

Changed Dabrafenib in Papillary thyroid cancer with BRAF V600E

Tier changed: 32. Comments changed: Phase 1/2 study. Dabrafenib stimulated radioiodine uptake in 60% (6/10) of patients with BRAF V600E-mutant iodine-refractory papillary thyroid cancer, with 2 partial responses and 4 stable disease after subsequent iodine-131 treatment.Not TGA approved; NCCN recommended.

Changed Vemurafenib in Papillary thyroid cancer with BRAF V600E

Tier changed: 32. Comments changed: Phase 2 trial. NCT01286753. Vemurafenib showed antitumour activity with a best overall response of 38.5% in patients with BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor.Not TGA approved; NCCN recommended.

Changed Encorafenib + Binimetinib in Colorectal adenocarcinoma with BRAF V600E, V600K: 3

Comments changed: Phase 2. NCT01543698. N=11. Encorafenib plus binimetinib showed confirmed responses in 18% (2/11) of mCRC. DCR at 6 months: 7/11 (64%).Phase 2. NCT01543698. N=11. ORR: 2/11 (18%). DCR at 6 months: 7/11 (64%)..

Changed Olaparib in Breast cancer with BRCA1 Oncogenic mutations: 3

Comments changed: Phase 2 TBCRC 048 study. Olaparib showed an ORR of 33% in cohort 1 and 31% in cohort 2, with confirmed responses seen in somatic BRCA1/2 (50%) mutation carriers, and median PFS of 6.3 months.TBCRC048; somatic BRCA.

Changed Cisplatin + Gemcitabine in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 3

Comments changed: Phase 2 trial. N=50. Cisplatin and gemcitabine with or without veliparib in germline BRCA1/2 or PALB2 positive PDAC. ORR was 74% (arm A), 65% (arm B) (P = .55). DCR was 100% (arm A) vs 78.3% (arm B) (P = .02). Median PFS 10.1 months (arm A) vs 9.7 months (arm B) (P = .73). Median OS 15.5 months (arm A) vs 16.4 months (arm B) (P = .6).PFS 10.1mo.

Changed Cisplatin + Veliparib in Triple-negative breast cancer with BRCA1 Oncogenic mutations (germline): 3

Comments changed: Randomised phase 2. SWOG S1416S1416 trial. NCT02595905. N=320. Cisplatin + veliparib significantly improved PFS in BRCA-like metastatic triple-negative breast cancer patients (5.9 months vs 4.2 months) but not in germline BRCA1/2-mutated or non-BRCA-like groups.. References changed: 36623515, 10.1200/JCO.2020.38.15_suppl.1001.

Changed Olaparib in Breast cancer with BRCA2 Oncogenic mutations: 3

Comments changed: Phase 2 TBCRC 048 study. Olaparib showed an ORR of 33% in cohort 1 and 31% in cohort 2, with confirmed responses seen in somatic BRCA1/2 (50%) mutation carriers, and median PFS of 6.3 months.TBCRC048; somatic BRCA.

Changed Cisplatin + Gemcitabine in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 3

Comments changed: Phase 2 trial. N=50. Cisplatin and gemcitabine with or without veliparib in germline BRCA1/2 or PALB2 positive PDAC. ORR was 74% (arm A), 65% (arm B) (P = .55). DCR was 100% (arm A) vs 78.3% (arm B) (P = .02). Median PFS 10.1 months (arm A) vs 9.7 months (arm B) (P = .73). Median OS 15.5 months (arm A) vs 16.4 months (arm B) (P = .6).PFS 10.1mo.

Changed Cisplatin + Veliparib in Triple-negative breast cancer with BRCA2 Oncogenic mutations (germline): 3

Comments changed: Randomised phase 2. SWOG S1416S1416 trial. NCT02595905. N=320. Cisplatin + veliparib significantly improved PFS in BRCA-like metastatic triple-negative breast cancer patients (5.9 months vs 4.2 months) but not in germline BRCA1/2-mutated or non-BRCA-like groups.. References changed: 36623515, 10.1200/JCO.2020.38.15_suppl.1001.

Changed Palbociclib in Dedifferentiated liposarcoma with CDK4 Amplification: 3

Comments changed: Phase 2 trial. NCT01209598. N=60. Palbociclib achieved a 12-week PFS of 66% in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma, exceeding the primary endpoint, with median PFS of 18 weeks.NCCN 2A. OncoKB LOE 2.

Changed Palbociclib in Well-differentiated liposarcoma with CDK4 Amplification: 3

Comments changed: Phase 2 trial. NCT01209598. N=60. Palbociclib achieved a 12-week PFS of 66% in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma, exceeding the primary endpoint, with median PFS of 18 weeks.NCCN 2A. OncoKB LOE 2.

Changed Pyrotinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: A775_G776insYVMA (Y772_A775dup), G776ins, G776R, G776C, P780_Y781insGSP (G778_P780dup), V777LA775_G776insYVMA, G776ins, G776R, G776C, P780_Y781insGSP, V777L.

Changed Afatinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: A775_G776insYVMA (Y772_A775dup), M774dupA775_G776insYVMA, M774dup.

Changed Poziotinib in Solid tumours, Non-small cell lung cancer with ERBB2 : 3

Alterations changed: A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup)A775_G776insYVMA, G778_P780dup.

Changed Poziotinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, Exon 20 insertion, Exon 20 mutationA775_G776insYVMA, G778_P780dup, G776delinsVC, Exon 20 insertion, Exon 20 mutation.

Changed Tarloxotinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: Exon 20 insertion, A775_G776insYVMA (Y772_A775dup).

Changed Poziotinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: Exon 20 insertion, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, V777_G778insVExon 20 insertion, A775_G776insYVMA, P780_Y781insGSP, G776delinsVC, V777_G778insV.

Changed Pyrotinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: Oncogenic mutations, A775_G776insYVMA (Y772_A775dup), exon 20 insertionOncogenic mutations, A775_G776insYVMA, exon 20 insertion.

Changed Ado-Trastuzumab Emtansine in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: Oncogenic mutations, V659E, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G778insCPG, G776delinsVC, exon 20 insertionOncogenic mutations, V659E, A775_G776insYVMA, G778_P780dup, G778insCPG, G776delinsVC, exon 20 insertion.

Changed Afatinib, Dacomitinib, Pyrotinib, Poziotinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: P780_Y781insGSP (G778_P780dup).

Changed Dacomitinib in Non-small cell lung cancer with ERBB2 : 3

Alterations changed: P780_Y781insGSP (G778_P780dup).

Changed Trastuzumab deruxtecan in Solid tumours with ERBB2 : 3

Alterations changed: S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, A775_G776insYVMA (Y772_A775dup), L755S, P780_Y781insGSP (G778_P780dup), T862A, V842IS310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, A775_G776insYVMA, L755S, P780_Y781insGSP, T862A, V842I.

Changed Fulvestrant + Neratinib in Breast cancer with ERBB2 : 3

Alterations changed: S310F, S310Y, L755S, A775_G776insYVMA (Y772_A775dup), V777L, P780_Y781insGSP (G778_P780dup), L869RS310F, S310Y, L755S, A775_G776insYVMA, V777L, G778_P780dup, L869R.

Changed Temozolomide in Glioblastoma with MGMT Promoter methylation

Tier changed: 31. Comments changed: Standard of care. NCCN Category 1. MGMT promoter methylation in glioblastoma (45% of 206 cases) correlates with improved survival (HR, 0.45) and significant survival benefit when combined with temozolomide and radiotherapy (21.7 months vs 15.3 months), serving as an essential diagnostic, prognostic, and predictive biomarker without necessarily changing treatment recommendations.Standard of care. NCCN Category 1. Note MGMT status does not.

Changed Ibrutinib in Chronic lymphocytic leukaemia with TP53 Alteration: 3

Comments changed: Retrospective biomarker analysis of Phase 2 trial NCT01500733 (N=34) showed ibrutinib as first-line therapy for CLL with TP53 alterations achieved 61% progression-free survival and 79% overall survival at 6 years, with median time to disease progression of 53 months and 30% complete response rate.CR 30%.

Changed Crizotinib in Non-small cell lung cancer with ALK L1198F

Tier changed: 43. Comments changed: Case report. A patient with metastatic ALK-rearranged lung cancer developed resistance to crizotinib due to C1156Y mutation, responded to lorlatinib, but upon relapse, acquired L1198F mutation, resensitizing the tumor to crizotinib, allowing for successful retreatment with crizotinib.. References changed: 26698910, 28122866.

Changed Afatinib in Non-small cell lung cancer with ERBB2 : 4

Alterations changed: A775_G776insYVMA (Y772_A775dup).

Changed Afatinib in Non-small cell lung cancer with ERBB2 : 4

Alterations changed: A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776A775_G776insYVMA, G778_P780dup, G776.

Changed Poziotinib in Solid tumours, Non-small cell lung cancer with ERBB2 : 4

Alterations changed: D769H, D769Y, L755S, V777L, L755P, A775_G776insYVMA (Y772_A775dup), Exon 20 insertion, L786V, V842I, L869RD769H, D769Y, L755S, V777L, L755P, A775_G776insYVMA, Exon 20 insertion, L786V, V842I, L869R.

Changed Tarloxotinib in Solid tumours with ERBB2 : 4

Alterations changed: Exon 20 insertion, A775_G776insYVMA (Y772_A775dup).

Changed ELVN-002 in Solid tumour with ERBB2 : 4

Alterations changed: Exon 20 insertion, A775_G776insYVMA (Y772_A775dup), G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVCS310Y, R678Q, L755S, L755P, D769N, V773M, V777L, L869R, L869R and T798I, V842IExon 20 insertion, A775_G776insYVMA, G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVCS310Y, R678Q, L755S, L755P, D769N, V773M, V777L, L869R, L869R and T798I, V842I.

Changed Neratinib in Non-small cell lung cancer with ERBB2 : 4

Alterations changed: Oncogenic mutations, A775_G776insYVMA (Y772_A775dup), exon 20 insertionOncogenic mutations, A775_G776insYVMA, exon 20 insertion.

Changed Tucatinib in Solid tumour with ERBB2 : 4

Alterations changed: S310F, S310Y, R678Q, D769N, V773M, V777L, V842I, P780_Y781insGSP (G778_P780dup), V777_G778insGCS310F, S310Y, R678Q, D769N, V773M, V777L, V842I, P780_Y781insGSP, V777_G778insGC.

Changed Dacomitinib in Non-small cell lung cancer with ERBB2 : R2

Alterations changed: A775_G776insYVMA (Y772_A775dup).

Changed Dacomitinib in Solid tumours with ERBB2 : R2

Alterations changed: A775_G776insYVMA (Y772_A775dup).

Changed Osimertinib in Solid tumours with ERBB2 : R2

Alterations changed: A775_G776insYVMA (Y772_A775dup).

Changed Afatinib, Dacomitinib in Solid tumours, Non-small cell lung cancer with ERBB2 : R2

Alterations changed: A775_G776insYVMA (Y772_A775dup).

Changed Pyrotinib in Solid tumours with ERBB2 : R2

Alterations changed: A775_G776insYVMA (Y772_A775dup), L755P, L869RA775_G776insYVMA, L755P, L869R.

Changed Afatinib in Solid tumours with ERBB2 : R2

Alterations changed: A775_G776insYVMA (Y772_A775dup), L755P, P780insA775_G776insYVMA, L755P, P780ins.

Changed Tucatinib in Solid tumour with ERBB2 : R2

Alterations changed: Exon 20 insertion, T798M, A775_G776insYVMA (Y772_A775dup), G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVCExon 20 insertion, T798M, A775_G776insYVMA, G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVC.

Changed Lapatinib in Solid tumours with ERBB2 : R2

Alterations changed: L755M, L755S, A775_G776insYVMA (Y772_A775dup), G776delinsLC, G776delinsVC, S779_P780insVGS, V842I, T862AL755M, L755S, A775_G776insYVMA, G776delinsLC, G776delinsVC, S779_P780insVGS, V842I, T862A.

Changed Lapatinib in Solid tumours with ERBB2 : R2

Alterations changed: L755S, L755P, A775_G776insYVMA (Y772_A775dup), G778ins, P780_Y781insGSP (G778_P780dup), P780ins, V842I, L869RL755S, L755P, A775_G776insYVMA, G778ins, G778_P780dup, P780ins, V842I, L869R.

Changed Trastuzumab in Solid tumours with ERBB2 : R2

Alterations changed: R487W, L755P, L755S, D769Y, A775_G776insYVMA (Y772_A775dup), G776S, G776V, G776delinsLC, G776delinsVC, V777L, G778_S779insG, P780_Y781insGSP (G778_P780dup), L841V, V842I, N857S, T862A, D962N, P1199TR487W, L755P, L755S, D769Y, A775_G776insYVMA, G776S, G776V, G776delinsLC, G776delinsVC, V777L, G778_S779insG, P780_Y781insGSP, L841V, V842I, N857S, T862A, D962N, P1199T.

Changed MDM2 inhibitor, SAR405838 in Solid tumours, Liquid cancers with TP53 Oncogenic mutations: R2

Comments changed: Preclinical and clinical studies. Emergence of TP53 mutations is a resistance mechanism to HDM2 inhibition..

Tuesday, 20 May 2025 (Version: 20250520AU)

New AMT-562 in Solid tumours with ERBB3 Overexpression, Protein expression, Low protein expression: 4

Preclinical study. AMT-562, a novel HER3-targeting antibody-drug conjugate, demonstrated potent and durable antitumor responses in low HER3 expression xenograft models, including digestive system and lung tumors, and showed a favorable pharmacokinetic and safety profile. References: 37302522

Monday, 19 May 2025 (Version: 20250519AU)

Sunday, 18 May 2025 (Version: 20250518AU)

New tovorafenib in Solid tumours with BRAF N486_P490del, L485_P490del: 4

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New naporafenib in Solid tumours with BRAF V487_P492del, N486_P490del, L485_P490del: 4

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New exarafenib in Solid tumours with BRAF V487_P492del, N486_P490del, L485_P490del, G466V: 4

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New belvarafenib in Solid tumours with BRAF V600E, N486_P490del, L485_P490del: 4

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New encorafenib in Solid tumours with BRAF V600E, N486_P490del, L485_P490del, L597R: 4

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New PF-07709933 in Solid tumours with BRAF V600E, V600K, G469A, L597R, G466V: 4

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New plixorafenib in Solid tumours with BRAF V600E, V600K, N486_P490del, L597R, G466V: 4

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New Exarafenib in Solid tumours with BRAF G469A, L597R, L597V: R2

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New Naporafenib in Solid tumours with BRAF G469A, L597R, L597V, G466V: R2

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New Tovorafenib in Solid tumours with BRAF V487_P492del, G469A, L597R, L597V, G466V: R2

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New Plixorafenib in Solid tumours with BRAF V487_P492del, L485_P490del, G469A, L597V: R2

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New Belvarafenib in Solid tumours with BRAF V487_P492del, N486_P490del, G469A, L597R, L597V, G466V: R2

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New PF-07709933 in Solid tumours with BRAF V487_P492del, N486_P490del, L485_P490del, L597V: R2

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

New Encorafenib in Solid tumours with BRAF V600K, V487_P492del, G469A, L597V, G466V: R2

Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design. References: 38691346

Monday, 5 May 2025 (Version: 20250505AU)

New Trametinib in Juvenile myelomonocytic leukaemia with CBL Y371H, C384R: 3

Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months. References: 38867349

New Trametinib in Juvenile myelomonocytic leukaemia with KRAS A146T, G13D: 3

Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months. References: 38867349

New Trametinib in Juvenile myelomonocytic leukaemia with NRAS Q61L, G12S: 3

Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months. References: 38867349

New Trametinib in Juvenile myelomonocytic leukaemia with PTPN11 E76V, D61V: 3

Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months. References: 38867349

Sunday, 4 May 2025 (Version: 20250504AU)

New D3S-001 in Non-small cell lung cancer with KRAS G12C: 4

Preclinical study. D3S-001, a GDP-bound KRAS G12C inhibitor with rapid target engagement kinetics, showed robust antitumor activity preclinically and promising clinical efficacy. References: 38717075

Changed Dasatinib in Acute lymphoblastic leukaemia, Chronic myelogenous leukaemia with ABL1 E255K, E255V, F359C, F359I, F359V, Y253H, A337V, P465S: 2

Comments changed: Requires presence of the BCR-ABL fusion transcript by PCR in either peripheral blood or bone marrow., and not TGA approved by biomarker. OncoKB LOE 1..

Changed Lorlatinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: G1202R, I1171N, I1171S, I1171T, L1196M, L1196Q, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, I1171N and D1203N, F1174LG1202R, I1171N, I1171S, I1171T, L1196M, L1196Q, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L.

Changed Crizotinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: G1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196M, L1196Q, L1196Q, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and D1203N, F1174LG1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196M, L1196Q, L1196Q, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and D1203N, F1174L.

Changed Ceritinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: G1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196Q, G1202del, D1203N, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, I1171N and D1203N, F1174LG1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196Q, G1202del, D1203N, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L.

Changed Brigatinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: G1202R, T1151insT, C1156Y, I1171N, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and D1203N, F1174LG1202R, T1151insT, C1156Y, I1171N, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and D1203N, F1174L.

Wednesday, 30 April 2025 (Version: 20250430AU)

New Ensartinib in Solid tumours, Non-small cell lung cancer with ALK C1156Y, I1171N, V1180L, L1196Q, L1198F, D1203N, S1206F, S1206Y, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Zotizalkib in Solid tumours, Non-small cell lung cancer with ALK C1156Y, L1196Q, L1196Q, L1198F, G1202del, S1206F, S1206Y, E1210K, G1269A, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New NVL-655 in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Alectinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, C1156Y, F1174L, D1203N, S1206F, S1206Y, E1210K, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Ceritinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, F1174L, V1180L, L1196M, L1196Q, S1206F, S1206Y, G1269A, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Crizotinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, F1174L, V1180L, L1198F, G1202del, I1171N and L1198F, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Brigatinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, G1269A, I1171N and L1198F, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Lorlatinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, T1151insT, C1156Y, F1174L, V1180L, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New AMG-193 in Solid tumours with MTAP Deletion: 4

Preclinical study. The PRMT5 inhibitor showed confirmed partial responses in patients with MTAP-deleted solid tumors and demonstrated synergistic antitumor activity when combined with chemotherapies or sotorasib in preclinical models.". References: 39282709

New Lorlatinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, I1171N, I1171S, I1171T, L1196M, L1196Q, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Crizotinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196M, L1196Q, L1196Q, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and D1203N, F1174L: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Ceritinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196Q, G1202del, D1203N, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Brigatinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151insT, C1156Y, I1171N, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and D1203N, F1174L: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Alectinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151insT, I1171N, I1171S, I1171T, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, I1171N and D1203N, F1174L: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Ensartinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151insT, I1171S, I1171T, L1196Q, G1202del, E1210K, G1269A, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and D1203N: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New NVL-655 in Solid tumours, Non-small cell lung cancer with ALK I1171N and D1203N: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Zotizalkib in Solid tumours, Non-small cell lung cancer with ALK T1151insT, I1171N, I1171S, I1171T, V1180L, D1203N, I1171N and D1203N: R2

Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome. References: 39269178

New Zongertinib in Cholangiocarcinoma with NRG1 SDC4-NRG1 fusion: 4

Preclinical study & Case series. Zongertinib, a covalent HER2 TKI, exhibits antitumor activity in HER2-dependent NSCLC xenografts and induces objective responses in HER2-driven cancers, including SDC4-NRG1 fusion-positive cholangiocarcinoma and HER2 V777L-mutant breast cancer. References: 39248702

New Zongertinib in Breast cancer with ERBB2 V777L, Amplification, D769H, A775_Y776insYVMA, G776delinsVC, Exon 20 insertion, L755A, L755M, L755P, L755S, S310A, S310F, S310Y, V777L, V777M, V842I: 4

Preclinical study & Case series. Zongertinib, a covalent HER2 TKI, exhibits antitumor activity in HER2-dependent NSCLC xenografts and induces objective responses in HER2-driven cancers, including SDC4-NRG1 fusion-positive cholangiocarcinoma and HER2 V777L-mutant breast cancer. References: 39248702

New Zongertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, T790M: R2

Preclinical study & Case series. Zongertinib, a covalent HER2 TKI, exhibits antitumor activity in HER2-dependent NSCLC xenografts and induces objective responses in HER2-driven cancers, including SDC4-NRG1 fusion-positive cholangiocarcinoma and HER2 V777L-mutant breast cancer. References: 39248702

Monday, 28 April 2025 (Version: 20250428AU)

New BBO-8520 in Solid tumours with KRAS G12C: 4

Preclinical study. BBO-8520 is a covalent inhibitor that targets both GTP(ON) and GDP(OFF)-bound KRASG12C, achieving potent signaling inhibition in growth factor-activated states, efficient target engagement, and durable tumor regression across multiple models, including those resistant to KRASG12C(OFF)-only inhibitors. References: 39642212

Changed Therapy in Solid tumour with BRCA1 Oncogenic mutations: 4

Therapy changed: PalacaparibAZD9574.

Changed Therapy in Solid tumour with BRCA2 Oncogenic mutations: 4

Therapy changed: PalacaparibAZD9574.

Sunday, 27 April 2025 (Version: 20250427AU)

New HRS-4642 in Solid tumours, Non-small cell lung cancer with KRAS G12D: 4

Phase 1 trial. NCT05533463. HRS-4642 demonstrated anti-tumor activity against KRAS G12D-mutant cancers in vitro, in vivo, and dose escalation studies, with 2/9 responders in NSCLC. References: 38942026

Friday, 25 April 2025 (Version: 20250425AU)

New FHD-609 in Solid tumours with SMARCB1 Oncogenic mutations: 4

Phase 1. NCT04965753. N=55. FHD-609 demonstrated dose-dependent pharmacokinetic exposure, with a maximum tolerated dose of 40 mg twice weekly or 80 mg once weekly. Preliminary clinical activity included one partial response and eight cases of stable disease. References: 39660994

New BI-7273 in Synovial sarcoma with SS18 SS18-SSX fusion: 4

Preclinical study. BRD9 inhibition selectively targets and degrades the protein in synovial sarcoma, reversing oncogenic gene expression and demonstrating potent anti-tumor activity. References: 39660994

New FHD-609 in Synovial sarcoma with SS18 SS18-SSX fusion: 4

Phase 1. NCT04965753. N=55. FHD-609 demonstrated dose-dependent pharmacokinetic exposure, with a maximum tolerated dose of 40 mg twice weekly or 80 mg once weekly. Preliminary clinical activity included one partial response and eight cases of stable disease. References: 39660994

New FHD-609, FHD-286 in Small-cell lung cancer with POU2F3 Protein expression: 4

Preclinical study. Mammalian SWI/SNF complex activity in small cell lung cancer, specifically the POU2F3-positive subtype (SCLC-P), represents a targetable dependency. BRD9 degrader (FHD-609) and SMARCA4/2 inhibitor (FHD-286) independently inhibit tumor growth and improve survival in POU2F3-positive SCLC xenograft models, with enhanced efficacy when combined with first-line chemotherapy. References: 39029464

Thursday, 24 April 2025 (Version: 20250424AU)

Changed Amivantamab in Non-small cell lung cancer with EGFR Exon 20 insertion

Tier changed: 1B2. Comments changed: TGA approved. Not PBS Listed. FDA accelerated approval 2021-05-21. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months.Not TGA approved. FDA accelerated approval 2021-05-21. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months..

Changed Amivantamab + Carboplatin + Pemetrexed in Non-small cell lung cancer with EGFR Exon 20 insertion

Tier changed: 1B2. Comments changed: TGA approved. Not PBS Listed. Not FDA approved. Phase 3 trial. PAPILLON. NCT04538664. N=308. Amivantamab-chemotherapy (carboplatin-pemetrexed) was associated with superior progression-free survival (11.4 months versus 6.7 months) and a higher overall response rate (73% vs 47%) compared to chemotherapy alone in patients with advanced NSCLC with EGFR exon 20 insertions as first line treatment.Not TGA approved. Not FDA approved. Phase 3 trial. PAPILLON. NCT04538664. N=308. Amivantamab-chemotherapy (carboplatin-pemetrexed) was associated with superior progression-free survival (11.4 months versus 6.7 months) and a higher overall response rate (73% vs 47%) compared to chemotherapy alone in patients with advanced NSCLC with EGFR exon 20 insertions as first line treatment..

Changed Amivantamab in Non-small cell lung cancer with EGFR C797S, Exon 20 insertion

Tier changed: 32. Comments changed: Phase 1. JNJ-61186372 demonstrated a manageable safety profile with preliminary responses in advanced NSCLC patients with EGFR-driven third-generation TKI-relapsed and Exon20ins disease, achieving 28% ORR (25/88) at ≥ 700 mg dose..

Changed Poziotinib in Non-small cell lung cancer with EGFR S768I, A767_V769dup, P772dupDNP, S768_D770dup, D770insG, D770insY, H773Y, N771insH, D770delinsGY: 3

Comments changed: Phase 2. N=11. Poziotinib demonstrated a confirmed objective response rate of 64% in patients with NSCLC with EGFR exon 20 mutations, showing potent and clinically active inhibition of EGFR and HER2 exon 20 mutations..

Changed Amivantamab + Lazertinib in Non-small cell lung cancer with EGFR+MET EGFR:Exon 19 deletion and MET:amplification, EGFR:L858R and MET:amplification, EGFR:Exon 19 deletion and MET:exon 14 skipping mutation, EGFR:L858R and MET:exon 14 skipping mutation: 3

Comments changed: Phase 1. CHRYSALIS. Amivantamab + Lazertinib combination treatment after osimertinib relapse. In a dose expansion cohort (N=45), overall response rate (ORR) was 36%. Notably, patients with EGFR or MET-based resistance mechanisms identified by NGS demonstrated an ORR of 47% (17/45).Phase 1 CHRYSALIS. Combination treatment after osimertinib relapse. Dose expansion N=45. ORR 36%. The ORR in 17/45 (47%) with EGFR or MET-based resistance mechanism identified by NGS..

Changed Osimertinib + Savolitinib in Non-small cell lung cancer with EGFR+MET EGFR:Oncogenic mutations and MET:amplification: 3

Comments changed: Phase 1b. TATTON. NCT02143466. N=186. Osimertinib + savolitinib showed acceptable risk-benefit profile and encouraging antitumour activity in MET-amplified, EGFR mutation-positive NSCLC patients who progressed on EGFR TKIs, with ORR of 48% (Part B) and 64% (Part D).Phase 1B TATTON. Significant ORR.

Changed Capmatinib + Gefitinib in Non-small cell lung cancer with EGFR+MET MET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R: 3

Comments changed: Phase 1b/2 trial. NCT01610336. N=161. Capmatinib plus gefitinib demonstrated an ORR of 27%, with enhanced activity in high MET-amplified tumors (47%), using a recommended phase II dose of capmatinib 400 mg twice daily and gefitinib 250 mg once daily..

Changed Tepotinib + Gefitinib in Non-small cell lung cancer with EGFR+MET MET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R: 3

Comments changed: Phase 1b/2. INSIGHT. NCT01982955. N=73. Tepotinib + gefitinib showed similar PFS (4.9 vs 4.4 months) and OS (17.3 vs 18.7 months) to chemotherapy in EGFR-mutant NSCLC with MET overexpression or amplification, but improved outcomes were seen in subgroups with high MET overexpression (PFS: 8.3 vs 4.4 months; OS: 37.3 vs 17.9 months) and MET amplification (PFS: 16.6 vs 4.2 months; OS: 37.3 vs 13.1 months)..

Changed Nilotinib in Gastrointestinal stromal tumour with KIT Oncogenic mutations; Exon 11 mutation; Exon 9 mutation: 3

Comments changed: Phase 2. N=35. Nilotinib demonstrated a disease control rate of 29% at Week 24, with a median progression-free survival of 113 days, overall survival of 310 days, and an objective response rate of 3% in GIST patients previously resistant to imatinib and sunitinib.DCR 29% third line.

Changed Trametinib in Melanoma with NRAS Oncogenic mutations: 3

Comments changed: Retrospective study. N=33. MEK inhibitors showed 18.2% ORR and 48.5% DCR in pre-treated NRAS-mutated metastatic melanoma patients, with median PFS of 2.8 months and OS of 7.1 months. [Updated from 2020-06-11]METRIC subgroup. References changed: 3527208422663011.

Wednesday, 23 April 2025 (Version: 20250423AU)

New GV1001 + Gemcitabine + Capecitabine in Pancreatic adenocarcinoma with CCL11 Serum level high: 2

Phase 3. NCT02854072. N=148, GV1001 + gemcitabine/capecitabine improved OS (11.3 vs 7.5 months) and TTP (7.3 vs 4.5 months) in eotaxin-high patients with advanced PDAC. References: 37903909

New Cadonilimab + Anlotinib in Non-small cell lung cancer with CD274 Protein expression: 3

Phase Ib/II trial. NCT04646330. N=69. Cadonilimab and anlotinib demonstrated manageable safety and promising efficacy with an ORR of 51% (25/49) at 15mg/kg Q3W and 60% (12/20) at 10mg/kg Q3W as first-line treatment in advanced NSCLC. ORRs differed between PD-L1-positive (60.5%) and PD-L1-negative (42.3%) patients. PD-L1 expression was assessed by immunohistochemistry using PD-L1 IHC 22C3 pharmDx (Dako Omnis), with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%. High PD-L1 expression was not required for entry into the trial. References: 38110665

New Ponatinib + Asciminib in Chronic myelogenous leukaemia with ABL1 BCR-ABL1 fusion AND T315I AND E355G: 4

Case report. Ponatinib and asciminib combination therapy effectively overcame BCR-ABL1 T315I/E355G compound mutant resistance in a CML patient, with complete haematologic response achieved within 2 weeks. References: 39214096

New G007-LK, RK-582 in Colorectal adenocarcinoma with APC+PIK3CA APC:Oncogenic mutations AND PIK3CA:Oncogenic mutations: 4

Preclinical study. Tankyrase inhibitor sensitivity in colorectal cancer cells correlates with APC/PIK3CA mutations and beta-catenin status, suggesting potential predictive biomarkers. References: 37968472

New ADCT-701 in Neuroblastoma with DLK1 Protein expression: 4

Preclinical study. DLK1 is an immunotherapeutic target in neuroblastoma, characterized by high expression linked to super-enhancer activation. ADCT-701 antibody-drug conjugate demonstrating potent cytotoxicity in xenograft models. References: 39454577

New Abemaciclib + AZD8421 in Breast cancer with ESR1+TP53 ESR1:Protein expression AND TP53:Oncogenic mutations: 4

Preclinical study. In metastatic hormone receptor-positive breast cancer, TP53 loss and MDM2 amplification were associated with lack of long-term disease control . CDK2 inhibition overcomes p53 loss, leading to geroconversion and senescence. References: 39532066

New Ribociclib, BSJ-03-123 in Diffuse hemispheric glioma with H3F3A G34R, G34V: 4

Preclinical study and case report. CDK6 is a targetable vulnerability in diffuse hemispheric glioma (H3G34-mutant), with tumor cells demonstrating sensitivity to Ribociclib and a CDK6-specific degrader. This approach promotes more mature interneuron-like states and reduces tumor growth. In a 10-year-old patient, third-line treatment with ribociclib induced disease control for 17 months. References: 39232581

New ABBV-400 in Colorectal adenocarcinoma with MET Protein expression; Overexpression: 4

Phase 1. NCT05029882. N=122. ABBV-400 demonstrated preliminary efficacy with ORR of 15% at 2.4 mg/kg and 20% at 3.0 mg/kg Q3W, accompanied by a tolerable safety profile. ORR was correlated with c-Met expression. References: 10.1200/JCO.2024.42.16_suppl.3515

New Olaparib in Prostate cancer with BRCA2 Reversion mutations: R2

Biomarker analysis. In patient enrolled in TOPARP-B trial, reversion mutations were identified in 79% of BRCA2/PALB2-mutated tumors, correlating with improved radiological progression-free and overall survival. References: 39577422

New Abemaciclib, Palbociclib, Ribociclib in Breast cancer with ESR1+MDM2 ESR1:Protein expression AND MDM2:Amplification: R2

Preclinical study. In metastatic hormone receptor-positive breast cancer, TP53 loss and MDM2 amplification were associated with lack of long-term disease control . CDK2 inhibition overcomes p53 loss, leading to geroconversion and senescence. References: 39532066

New Abemaciclib, Palbociclib, Ribociclib in Breast cancer with ESR1+TP53 ESR1:Protein expression AND TP53:Oncogenic mutations: R2

Preclinical study. In metastatic hormone receptor-positive breast cancer, TP53 loss and MDM2 amplification were associated with lack of long-term disease control . CDK2 inhibition overcomes p53 loss, leading to geroconversion and senescence. References: 39532066

New FOLFOX + Bevacizumab + Durvalumab + Oleclumab in Colorectal adenocarcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: R2

Phase 1B/2. COLUMBIA-1. NCT04068610. N=59. Durvalumab + oleclumab added to FOLFOX and bevacizumab did not significantly improve ORR (61.5% vs 46.2%) in metastatic microsatellite-stable colorectal cancer. References: 39048638

New Olaparib in Prostate cancer with PALB2 Reversion mutations: R2

Biomarker analysis. In patient enrolled in TOPARP-B trial, reversion mutations were identified in 79% of BRCA2/PALB2-mutated tumors, correlating with improved radiological progression-free and overall survival. References: 39577422

Changed Pamiparib + AZD7762 with H3F3A G34R, G34V: 4

Cancer type(s) changed: Diffuse hemispheric gliomaHigh-grade gliomas

Changed eFT508 with MYD88 Gain-of-function mutations: 4

Cancer type(s) changed: Diffuse large B-cell lymphomaSolid tumours

Changed Osimertinib in Non-small cell lung cancer with EGFR C797S, C797G: R2

References changed: 25964297; 30073261; 37938348.

Changed Pazopanib in Gastrointestinal stromal tumour with KIT D816V, Y823D: R2

References changed: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_PharmR.pdfOther.

Changed Osimertinib in Non-small cell lung cancer with MET Amplification: R2

Comments changed: Secondary resistance post Osimertinib. MET amplification determined by FISH, liquid biopsy.Secondary resistance post Osimertinib. Amplification determined by FISH.. References changed: 27252416; 37938348.

Monday, 21 April 2025 (Version: 20250421AU)

New Pazopanib in Gastrointestinal stromal tumour with KIT D816V, Y823D: R2

AccessFDA data. GW786034B: weak activity against V654A mutant (IC50=1.45 uM); inactive against D816V (IC50 >10 uM) and Y823D (IC50 >5 uM) mutations. References: Other

Monday, 14 April 2025 (Version: 20250414AU)

New Olaparib in Uterine serous carcinoma with BRIP1 Oncogenic mutations, Q554Hfs*35: 4

Case report. Olaparib monotherapy resulted in a complete response lasting over nine months in a patient with BRIP1-mutated high-grade serous endometrial cancer. References: 32923896

New VX-970 in Adenoid cystic carcinoma with MYB Overexpression; MYB-NFIB fusion: 4

Preclinical study. ATR kinase inhibitor VX-970 induced apoptosis in MYB-positive adenoid cystic carcinoma cells and growth inhibition in ACC patient-derived xenografts, identifying ATR as a potential therapeutic target downstream of MYB activation. References: 32001675

Sunday, 13 April 2025 (Version: 20250413AU)

New Sacituzumab Govitecan in Breast cancer with TACSTD2 T256R: R2

Sacituzumab govitecan resistance mechanisms identified through RNA and whole-exome sequencing of pre-treatment and post-progression specimens, including TROP2T256R missense mutation and TOP1 E418K resistance mutation. References: 34404686

New Sacituzumab Govitecan in Breast cancer with TOP1 E418K: R2

Sacituzumab govitecan resistance mechanisms identified through RNA and whole-exome sequencing of pre-treatment and post-progression specimens, including TROP2T256R missense mutation and TOP1 E418K resistance mutation. References: 34404686

Thursday, 10 April 2025 (Version: 20250410AU)

Changed Therapy in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 1

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Breast cancer with ERBB2 Amplification, Overexpression: 1B

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Breast cancer with ERBB2 Amplification; Overexpression: 1B

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Tovorafenib in Low-grade gliomas with BRAF V600, V600E, KIAA1549-BRAF fusion,Fusion

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. Phase 2. FIREFLY-1. PNOC026. n=77. BRAF-altered, relapsed/refractory pediatric low-grade glioma. The primary endpoint was met: ORR was 46/69 (67%) by RANO-HGG criteria. DOR was 16.6 months..

Changed Neratinib + Capecitabine in Breast cancer with ERBB2 Amplification: 2

Comments changed: Not TGA approved. FDA approved. NALA: Phase 3 trial in patient previously treated with two or more lines of HER2-directed regimens, median PFS of neratinib was superior over lapatinib.Not TGA approved. FDA approved. NALA: Phase III trial in patient previously treated with two or more lines of HER2-directed regimens, median PFS of neratinib was superior over lapatinib..

Changed Trastuzumab deruxtecan in Biliary tract cancer with ERBB2 Overexpression

Tier changed: 23. Comments changed: Not TGA approved. FDA approved (accelerated). Phase 2. NCT04482309. DESTINY-PanTumor02. N=267. Trastuzumab deruxtecan showed an ORR of 37.1% with a median DOR of 11.3 months, PFS of 6.9 months, and OS of 13.4 months in HER2-expressing solid tumors; greatest benefit was seen in the IHC 3+ population. In in biliary tract cancers, the ORR was 56% in the IHC 3+ group. No responses were seen in the IHC 2+ population.Phase 2. NCT04482309. DESTINY-PanTumor02. ORR in biliary.

Changed Therapy in Colorectal cancer with ERBB2 Overexpression: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Trastuzumab deruxtecan in Cervical cancer, Endometrial cancer, Ovarian cancer, Bladder cancer, Solid tumours except Pancreatic adenocarcinoma, Biliary tract cancers with ERBB2 Overexpression, Protein expression

Tier changed: 23. Comments changed: Phase 2. NCT04482309. DESTINY-PanTumor02 trial. N=267. Trastuzumab deruxtecan showed an ORR of 37% with a median DOR of 11.3 months, PFS of 6.9 months, and OS of 13.4 months in HER2-expressing solid tumors; greatest benefit was seen in the IHC 3+ population..

Changed Therapy in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression, Protein expression AND Amplification: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Non-small cell lung cancer with ERBB2 S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, P780_Y781insGSP, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Pemigatinib in Myelodysplastic/myeloproliferative diseases, Myeloproliferative diseases, Acute lymphoblastic leukaemia, Acute myeloid leukaemia with FGFR1 Rearrangement, Fusion: 2

Comments changed: Not TGA approved. FDA approved. Phase 2. FIGHT-203. NCT03011372. CR was achieved in 14 of 18 patients with chronic phase (78%) and 2 in 4 patients with blast Phase 1n the marrow. 22 of 28 patients (79%) achieved complete cytogenetic response.Not TGA approved. FDA approved. Phase 2. FIGHT-203. NCT03011372. CR was achieved in 14 of 18 patients with chronic phase (78%) and 2 in 4 patients with blast phase in the marrow. 22 of 28 patients (79%) achieved complete cytogenetic response..

Changed Infigratinib in Cholangiocarcinoma with FGFR2 Fusions: 2

Comments changed: Not TGA approved. FDA accelerated approved for use in second-line and beyond. Phase 2 study (NCT02150967) with N=108. ORR: 23%. Median PFS 7.3 months.Not TGA approved. FDA accelerated approved for use in second-line and beyond. Phase II study (NCT02150967) with N=108. ORR: 23%. Median PFS 7.3 months..

Changed Cobimetinib, Trametinib in Histiocytosis with MAP2K1 P142L, P124Q, Q56P, P105_107del: 2

Comments changed: Phase 2 Umbrella studyPhase II Umbrella study.

Changed Taselisib + Fulvestrant in Breast cancer with PIK3CA Oncogenic mutations: 2

Comments changed: Not TGA approved. Not FDA approved. Positive Phase 3 SANDPIPER with regards to median PFS (7.4 months) over placebo (5.4 mo). However, taselisib has limited clinical utility given safety profile and low magnitude of clinical benefit.Not TGA approved. Not FDA approved. Positive Phase III SANDPIPER with regards to median PFS (7.4 months) over placebo (5.4 mo). However, taselisib has limited clinical utility given safety profile and low magnitude of clinical benefit..

Changed Vemurafenib + Cobimetinib in Papillary craniopharyngioma with BRAF V600E: 3

Comments changed: Phase 2 Alliance A071601. NCT03224767. Objective response in 15 of 16 patients.Phase II Alliance A071601. NCT03224767. Objective response in 15 of 16 patients..

Changed Ceralasertib + Olaparib in Ovarian cancer with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 3

Comments changed: Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 50% (6/12).Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 50% (6/12)..

Changed Ceralasertib + Olaparib in Ovarian cancer with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 3

Comments changed: Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13)..

Changed Odronextamab in Follicular lymphoma with CD20 Protein expression: 3

Comments changed: Phase 2 ELM-2 trial. NCT03888105. N=128. Odronextamab achieved an ORR of 80% and CR rate of 73.4%, with a median DoR of 25.1 months, PFS of 20.7 months, and OS not reached in patients with relapsed or refractory follicular lymphoma. Note of level of CD20 expression was not associated with responses irrespective at baseline, CRs seen in no or low proportions of CD20-positive cells.Phase II ELM-2 trial. NCT03888105. N=128. Odronextamab achieved an ORR of 80% and CR rate of 73.4%, with a median DoR of 25.1 months, PFS of 20.7 months, and OS not reached in patients with relapsed or refractory follicular lymphoma. Note of level of CD20 expression was not associated with responses irrespective at baseline, CRs seen in no or low proportions of CD20-positive cells..

Changed Durvalumab in Urothelial carcinoma with CD274 Protein expression: 3

Comments changed: TGA conditionally approved but not PBS reimbursed. ORR difference was found between PD-L1 high vs low groups. PD-L1 positivity is defined as >= 25% of either tumour or immune cells staining for PD-L1 using Ventana SP-263 assay. NB: TGA approval was based on response rate. NCT01693562. Note FDA Approval withdrawn in Feb 2021, based on Phase 3 DANUBE trial results.TGA conditionally approved but not PBS reimbursed. ORR difference was found between PD-L1 high vs low groups. PD-L1 positivity is defined as >= 25% of either tumour or immune cells staining for PD-L1 using Ventana SP-263 assay. NB: TGA approval was based on response rate. NCT01693562. Note FDA Approval withdrawn in Feb 2021, based on Phase III DANUBE trial results..

Changed Osimertinib in Non-small cell lung cancer with EGFR G719, L747S, S768I, L861Q: 3

Comments changed: Phase 2 KCSG-LU15-09: Osimertinib for Patients With NSCLC harboring uncommon EGFR Mutations. N=37, ORR 50%Phase II KCSG-LU15-09: Osimertinib for Patients With NSCLC harboring uncommon EGFR Mutations. N=37, ORR 50%.

Changed Poziotinib in Solid tumours, Non-small cell lung cancer with ERBB2 A775_G776insYVMA, G778_P780dup: 3

Comments changed: Phase 2. ORR 43% (5/12) and DCR 83%. NCT03066206.Phase II. ORR 43% (5/12) and DCR 83%. NCT03066206..

Changed Therapy in Biliary tract cancer with ERBB2 Amplification, Overexpression: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Dacomitinib in Non-small cell lung cancer with ERBB2 G778_P780dup: 3

Comments changed: Phase 2 trial: 2/2 patients harbouring the mutation responded to Dacomitinib with prolonged response.Phase II trial: 2/2 patients harbouring the mutation responded to Dacomitinib with prolonged response..

Changed Therapy in Non-small cell lung cancer with ERBB2 Kinase domain mutation: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed BAY 2927088 in Non-small cell lung cancer with ERBB2 Oncogenic mutations: 3

Comments changed: Phase 1/2 SOHO-01 study. NCT05099172. N=34. BAY 2927088 led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months.Phase I/II SOHO-01 study. NCT05099172. N=34. BAY 2927088 led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months..

Changed IMU-131 in Solid tumours with ERBB2 Overexpression, Protein expression, Amplification: 3

Comments changed: Phase 1b Trial IMU.ACS.001. NCT02795988. Objective response seen in 5 of 14 patients.Phase Ib Trial IMU.ACS.001. NCT02795988. Objective response seen in 5 of 14 patients..

Changed Therapy in Non-small cell lung cancer with ERBB2 Protein expression AND NOT Oncogenic mutations, Overexpression AND NOT Oncogenic mutations: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Solid tumours with ERBB2 S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, A775_G776insYVMA, L755S, P780_Y781insGSP, T862A, V842I: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Colorectal adenocarcinoma with ERBB2+KRAS ERBB2:Amplification and ERBB2:Protein expression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E, ERBB2:Overexpression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Camizestrant in Breast cancer with ESR1 E380Q, S463P, V422del, L536P, L536H, Y537C, Y537D, Y537N, Y537S, D538G: 3

Comments changed: Phase 1. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44).Phase I. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44)..

Changed Elacestrant in Breast cancer with ESR1 Protein expression: 3

Comments changed: Phase 1. N=50 with ORR 19%. 52% treated with prior SERD.Phase I. N=50 with ORR 19%. 52% treated with prior SERD..

Changed Camizestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Comments changed: Phase 1. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44).Phase I. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44)..

Changed Imlunestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Comments changed: Phase 1a/Ib EMBER study. NCT04188548. N=262. Imlunestrant showed manageable safety profile and preliminary antitumor activity in ER+/HER2- advanced breast cancer, with median PFS of 7.2 months (monotherapy) and up to 19.2 months (in combination with targeted therapy).Phase Ia/Ib EMBER study. NCT04188548. N=262. Imlunestrant showed manageable safety profile and preliminary antitumor activity in ER+/HER2- advanced breast cancer, with median PFS of 7.2 months (monotherapy) and up to 19.2 months (in combination with targeted therapy)..

Changed Ceralasertib + Olaparib in Ovarian cancer with Homologous Recombination Deficiency Score High: 3

Comments changed: Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13)..

Changed Tipifarnib in Head and neck squamous cell carcinoma , Salivary gland cancers, Urothelial carcinoma with HRAS Oncogenic mutations: 3

Comments changed: Single arm Phase 2 of Tipifarnib in R/M HNSCC patients. ORR 55%. mPFS tipifarnib: 5.6 months. KO-TIP-001Single arm Phase II of Tipifarnib in R/M HNSCC patients. ORR 55%. mPFS tipifarnib: 5.6 months. KO-TIP-001.

Changed Olaparib in Chondrosarcoma with IDH1 R132C, R132S, R132: 3

Comments changed: Phase 2 Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified.Phase II Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified..

Changed Olaparib in Epithelioid haemangioendothelioma with IDH2 V305M: 3

Comments changed: Phase 2 Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified.Phase II Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified..

Changed Nilotinib in Melanoma with KIT Exon 11 mutation, Exon 11 deletion, L576P, K642E, I817L, V559A: 3

Comments changed: Phase 2 UN10-06 trial. Exon 11 mutation ORR 29%. One responder I817L.Phase II UN10-06 trial. Exon 11 mutation ORR 29%. One responder I817L..

Changed Garsorasib in Colorectal adenocarcinoma with KRAS G12C: 3

Comments changed: Phase 1/2 (NCT04585035). N=24. D-1553 demonstrated a activity in heavily pretreated CRC with KRAS G12C mutations. Confirmed ORR was 21%. DCR was 96%.Phase I/II (NCT04585035). N=24. D-1553 demonstrated a activity in heavily pretreated CRC with KRAS G12C mutations. Confirmed ORR was 21%. DCR was 96%..

Changed Tepotinib in Non-small cell lung cancer with MET Amplification: 3

Comments changed: Phase 2 VISION Cohort B. N=24. MET gene copy number >=2.5 by liquid biopsy. No exon 14 skipping mutations. ORR 42%. In previously untreated patient, ORR 71%.Phase II VISION Cohort B. N=24. MET gene copy number >=2.5 by liquid biopsy. No exon 14 skipping mutations. ORR 42%. In previously untreated patient, ORR 71%..

Changed Temozolomide + Ipilimumab + Nivolumab in Colorectal adenocarcinoma with MGMT Loss of protein expression, Promoter methylation: 3

Comments changed: Phase 2 trial. MAYA. NCT03832621. In pre-treated, MGMT-silenced MSS colorectal cancer, sequencing temozolomide by priming followed by immune checkpoint blockade may induce durable clinical benefit. PFS at 8 months was 36%. Median PFS was 7.0 months. Medial OS was 18.4 months.Phase II trial. MAYA. NCT03832621. In pre-treated, MGMT-silenced MSS colorectal cancer, sequencing temozolomide by priming followed by immune checkpoint blockade may induce durable clinical benefit. PFS at 8 months was 36%. Median PFS was 7.0 months. Medial OS was 18.4 months..

Changed Ipilimumab + Nivolumab in Prostate cancer with Microsatellite Instability High: 3

Comments changed: Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months.Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months..

Changed Ipilimumab + Nivolumab in Prostate cancer with Mismatch repair Deficient: 3

Comments changed: Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months.Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months..

Changed Mirdametinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

Comments changed: NF106. Phase 2 trial. N=19. NCT02096471. ORR 42%; CBR 95% with significant durable decreases in pain ratings in patients with NF1-related plexiform neurofibromas.NF106. Phase II trial. N=19. NCT02096471. ORR 42%; CBR 95% with significant durable decreases in pain ratings in patients with NF1-related plexiform neurofibromas..

Changed Cobimetinib in Histiocytosis with NRAS Oncogenic mutations: 3

Comments changed: Phase 2 Umbrella studyPhase II Umbrella study.

Changed Binimetinib in Melanoma with NRAS Oncogenic mutations: 3

Comments changed: Not TGA approved. Positive Phase 3 NEMO result, but overall small absolute PFS gain. FDA application withdrawn and NCCN 2B. Revised Tier 3Not TGA approved. Positive Phase III NEMO result, but overall small absolute PFS gain. FDA application withdrawn and NCCN 2B. Revised Tier 3.

Changed Binimetinib in Melanoma with NRAS Oncogenic mutations: 3

Comments changed: Phase 2. Small sample sizePhase II. Small sample size.

Changed KL590586 in Solid tumour with RET Fusions, Oncogenic mutations: 3

Comments changed: Phase 1 KL400-I/II-01 trial. NCT05265091. In the dose expansion part (n=69), ORR was 64% in RET altered tumors including NSCLC, MTC, pancreatic cancer and ovarian cancer. ORR in systemic pretreated NSCLC was 63%, DCR 91%. ORR in treatment nave NSCLC was 76% with DCR of 92%. CNS DCR was 100%.Phase I KL400-I/II-01 trial. NCT05265091. In the dose expansion part (n=69), ORR was 64% in RET altered tumors including NSCLC, MTC, pancreatic cancer and ovarian cancer. ORR in systemic pretreated NSCLC was 63%, DCR 91%. ORR in treatment nave NSCLC was 76% with DCR of 92%. CNS DCR was 100%..

Changed Adavosertib in Uterine serous carcinoma with TP53 Oncogenic mutations: 3

Comments changed: Single arm Phase 2 trial with adavosertib in USC with TP53 alterations (predefined hypothesis). ORR 29% with PFS at 6 months 47%. Note: TP53 mutation was prespecified in the hypothesis of study, although TP53 alone is likely insufficient for predicting sensitivity to WEE1 inhibition.Single arm phase II trial with adavosertib in USC with TP53 alterations (predefined hypothesis). ORR 29% with PFS at 6 months 47%. Note: TP53 mutation was prespecified in the hypothesis of study, although TP53 alone is likely insufficient for predicting sensitivity to WEE1 inhibition..

Changed Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA1 Oncogenic mutations: 4

Comments changed: Phase 1b. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response.Phase Ib. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response..

Changed Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA2 Oncogenic mutations: 4

Comments changed: Phase 1b. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response.Phase Ib. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response..

Changed Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab in Ovarian cancer with CD274 Protein expression: 4

Comments changed: IMagyn050/GOG3015/ENGOT-OV39: Phase 3 trial of Chemotherapy and Bevacizumab with or without Atezolizumab. In intention-to-treat population, the median PFS was 19.5 vs 18.4 months (for IO+Chemo+Bevacizumab vs Chemo+Bevacizumab) respectively. Exploratory analysis as shown in PFS in subgroup analysis suggests that improvement in small population with IC >= 5% (HR 0.64) and TC >= 1% (HR 0.41).IMagyn050/GOG3015/ENGOT-OV39: Phase III trial of Chemotherapy and Bevacizumab with or without Atezolizumab. In intention-to-treat population, the median PFS was 19.5 vs 18.4 months (for IO+Chemo+Bevacizumab vs Chemo+Bevacizumab) respectively. Exploratory analysis as shown in PFS in subgroup analysis suggests that improvement in small population with IC >= 5% (HR 0.64) and TC >= 1% (HR 0.41)..

Changed Dacomitinib in Glioblastoma with EGFR Amplification AND G598V: 4

Comments changed: Phase 2: Dacomitinib was not effecitive in EGFR-amplified GBM (5/30 patients in arm B achieved PFS6 and did not meet the primary endpoint).Phase II: Dacomitinib was not effecitive in EGFR-amplified GBM (5/30 patients in arm B achieved PFS6 and did not meet the primary endpoint)..

Changed E-EDV-D682 in Pancreatic adenocarcinoma with EGFR Protein expression, Overexpression: 4

Comments changed: Interim data from Phase 1/2 ACTRN12619000385145. N=9. Confirmed response at 4 months in 4 of 5 patients. CBR 8 weeks 89%.Interim data from Phase I/II ACTRN12619000385145. N=9. Confirmed response at 4 months in 4 of 5 patients. CBR 8 weeks 89%..

Changed Therapy in Gastric cancer, Gastroesophageal junction adenocarcinoma, Colorectal adenocarcinoma with ERBB2 Amplification; Alteration: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Non-small cell lung cancer with ERBB2 Overexpression, Amplification: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Breast cancer with ERBB2 protein expression and NOT amplification: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Biliary tract cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed MRG004A in Solid tumours with F3 Protein expression: 4

Comments changed: Phase 1/2 study. N=63. MRG004A showed antitumor activity in heavily pretreated patients with solid tumors, including pancreatic cancer (ORR 33%, DCR 83%) at 2mg/kg.Phase I/II study. N=63. MRG004A showed antitumor activity in heavily pretreated patients with solid tumors, including pancreatic cancer (ORR 33%, DCR 83%) at 2mg/kg..

Changed Rucaparib in Prostate cancer with FANCA Loss-of-function mutations: 4

Comments changed: Phase 2 TITRON2Phase II TITRON2.

Changed Infigratinib in Lung squamous cell carcinoma with FGFR1 Amplification: 4

Comments changed: Responses in Phase 1 dose expansionResponses in Phase I dose expansion.

Changed Erdafitinib in Lung squamous cell carcinoma with FGFR1 Amplification, Oncogenic mutations: 4

Comments changed: Phase 2 trial (FIND)Phase II trial (FIND).

Changed Futibatinib in Solid tumours with FGFR1 N546D: 4

Comments changed: Phase 1 trial. NCT02052778. FOENIX-101. N = 86. Futibatinib, a selective FGFR1-4 inhibitor, was evaluated in patients with refractory solid tumors with partial responses observed in FGFR2 fusion-positive intrahepatic cholangiocarcinoma (n = 3) and FGFR1-mutant primary brain tumor (n = 2).Phase I trial. NCT02052778. FOENIX-101. N = 86. Futibatinib, a selective FGFR1-4 inhibitor, was evaluated in patients with refractory solid tumors with partial responses observed in FGFR2 fusion-positive intrahepatic cholangiocarcinoma (n = 3) and FGFR1-mutant primary brain tumor (n = 2)..

Changed Erdafitinib in Lung squamous cell carcinoma with FGFR2 Oncogenic mutations: 4

Comments changed: Phase 2 trial (FIND)Phase II trial (FIND).

Changed Erdafitinib in Lung squamous cell carcinoma with FGFR3 Amplification, Fusion, Oncogenic mutations: 4

Comments changed: Phase 2 trial (FIND)Phase II trial (FIND).

Changed Erdafitinib in Solid tumours with FGFR3 Amplification, Fusion, Oncogenic mutations and NOT V565 and NOT V550: 4

Comments changed: NCT01703481, Phase 1 dose escalation and expansion. ORR 46% in urothelial carcinoma and 27% in cholangiocarcinoma. <10% for the rest of tumour types.NCT01703481, Phase I dose escalation and expansion. ORR 46% in urothelial carcinoma and 27% in cholangiocarcinoma. <10% for the rest of tumour types..

Changed Trametinib in Non-small cell lung cancer with KRAS Oncogenic mutations: 4

Comments changed: Phase 2, ORR 12% but worse PFS than docetaxelPhase II, ORR 12% but worse PFS than docetaxel.

Changed Binimetinib in Solid tumours with KRAS Oncogenic mutations: 4

Comments changed: Phase 1, ORR 3%Phase I, ORR 3%.

Changed Olaparib in Pancreatic adenocarcinoma with PALB2 Oncogenic mutations (germline): 4

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. One responder seen in PALB2 germline mutation.Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. One responder seen in PALB2 germline mutation..

Changed Fulvestrant + Copanlisib in Breast cancer with PIK3CA Oncogenic mutations: 4

Comments changed: OncoKB LOE 3; Ongoing Phase 1/2 trialOncoKB LOE 3; Ongoing Phase I/II trial.

Changed PRT3789 in Solid tumours with SMARCA4 Oncogenic mutation: 4

Comments changed: Phase 1. NCT05639751. PRT3789 selectively targets SMARCA4-deficient cells with anti-tumor activity and synergistic effects with therapies.Phase I. NCT05639751. PRT3789 selectively targets SMARCA4-deficient cells with anti-tumor activity and synergistic effects with therapies..

Changed PLX2853, PLX2853 + carboplatin in Ovarian Cancer with ARID1A Oncogenic mutation: R2

Comments changed: Phase 1b/IIa trial. NCT02794586. N=37. PLX2853 monotherapy and combination therapy with carboplatin demonstrated a best ORR of 1 PR (7%). The trial did not meet the prespecified response criteria.Phase Ib/IIa trial. NCT02794586. N=37. PLX2853 monotherapy and combination therapy with carboplatin demonstrated a best ORR of 1 PR (7%). The trial did not meet the prespecified response criteria..

Changed Olaparib in Pancreatic adenocarcinoma with ARID1A Oncogenic mutations: R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. ARID1A (N=3)Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. ARID1A (N=3).

Changed Olaparib in Pancreatic adenocarcinoma with ATM Oncogenic mutations, Oncogenic mutations (germline): R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. In ATM subgroup, response was seen in 1/14 patients with ATM mutation (somatic)Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. In ATM subgroup, response was seen in 1/14 patients with ATM mutation (somatic).

Changed Ipilimumab + Nivolumab in Prostate cancer with BRCA2 Oncogenic mutation: R2

Comments changed: Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies.Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies..

Changed Fulvestrant + Palbociclib in Breast cancer with CCNE1 mRNA expression: R2

Comments changed: Exploratory analysis from Phase 3 PEARL study: high tumour CCNE mRNA expression is correlated to relevanceExploratory analysis from Phase III PEARL study: high tumour CCNE mRNA expression is correlated to relevance.

Changed Ipilimumab + Nivolumab in Prostate cancer with CDK12 Oncogenic mutation: R2

Comments changed: Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies.Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies..

Changed Dacomitinib in Glioblastoma with EGFR Amplification: R2

Comments changed: Phase 2: Dacomitinib was not effecitive in EGFR-amplified GBM. A subset experienced a durable, clinically meaningful benefit (2/4 G598V with TTP>=6 months)Phase II: Dacomitinib was not effecitive in EGFR-amplified GBM. A subset experienced a durable, clinically meaningful benefit (2/4 G598V with TTP>=6 months).

Changed Therapy in Colorectal adenocarcinoma with ERBB2 No protein expression, Low protein expression: R2

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Colorectal cancer with ERBB2 Protein expression AND Amplification AND NOT Overexpression: R2

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Therapy in Colorectal cancer with ERBB2+KRAS ERBB2:Overexpression AND KRAS:Oncogenic mutation, ERBB2:Protein expression AND KRAS:Oncogenic mutation: R2

Therapy changed: Fam-trastuzumab deruxtecan-nxki.

Changed Olaparib in Pancreatic adenocarcinoma with FANCD2 Oncogenic mutations, Oncogenic mutations (germline): R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold..

Changed Olaparib in Cholangiocarcinoma with IDH1 R132C, R132: R2

Comments changed: Phase 2 Basket trial. Olaparib for IDH mutations. No responders in four cholangiocarcinoma cases (3 cases with R132C).Phase II Basket trial. Olaparib for IDH mutations. No responders in four cholangiocarcinoma cases (3 cases with R132C)..

Changed Nilotinib in Melanoma with KIT Amplification: R2

Comments changed: Phase 2 UN10-06 trial. In KIT amplification only subgroup, only 1/15 response with with DOR of 5 weeks only (ORR 6%). Gene co-mutation status was not available in the case.Phase II UN10-06 trial. In KIT amplification only subgroup, only 1/15 response with with DOR of 5 weeks only (ORR 6%). Gene co-mutation status was not available in the case..

Changed Nilotinib in Melanoma with KIT Exon 13 mutation: R2

Comments changed: Phase 2 UN10-06 trial. In KIT exon 13 mutation subgroup, 0/15 response. Gene co-mutation status was not available in the case.Phase II UN10-06 trial. In KIT exon 13 mutation subgroup, 0/15 response. Gene co-mutation status was not available in the case..

Changed Imatinib in Adenoid cystic carcinoma with KIT Overexpression: R2

Comments changed: Phase 2 consortium-based study. N=15. ORR 0%.Phase II consortium-based study. N=15. ORR 0%..

Changed Afatinib in Colorectal adenocarcinoma with KRAS Oncogenic mutations: R2

Comments changed: Randomised Phase 2 trial. No activities is seen in Afatinib arm (ORR 0%, of 36) in KRAS mutant group.Randomised phase II trial. No activities is seen in Afatinib arm (ORR 0%, of 36) in KRAS mutant group..

Changed Olaratumab + Doxorubicin in Soft tissue sarcomas with PDGFRA Overexpression: R2

Comments changed: ANNOUNCE trial. Negative Phase 3. No benefit over doxorubicin in PDGFRA overexpression subgroup.ANNOUNCE trial. Negative Phase III. No benefit over doxorubicin in PDGFRA overexpression subgroup..

Changed Everolimus in Solid tumours with PIK3CA Amplification, Oncogenic mutations: R2

Comments changed: Phase 2 Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.Phase II Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months..

Changed Everolimus in Solid tumours with PTEN Loss of protein expression, Loss-of-function mutations: R2

Comments changed: Phase 2 Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.Phase II Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months..

Changed Olaparib in Pancreatic adenocarcinoma with PTEN Oncogenic mutations: R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. PTEN (N=2)Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. PTEN (N=2).

Changed Olaparib in Pancreatic adenocarcinoma with RAD51C Oncogenic mutations, Oncogenic mutations (germline): R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold..

Changed Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Microsatellite Instability Tumour Mutational Burden:High and NOT Microsatellite instability:high: R2

Comments changed: Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB.Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB..

Changed Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Mismatch repair Tumour Mutational Burden:High and NOT Mismatch repair:deficient: R2

Comments changed: Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB.Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB..

Monday, 31 March 2025 (Version: 20250331AU)

New Darovasertib in Uveal melanoma with GNAQ Oncogenic mutations: 4

Phase 2 study of neoadjuvant/adjuvant darovasertib for localized ocular melanoma, N=15, median tumor shrinkage was 11.2%/7.6%/22.7% after 1 month and 31.7%/11.9%/45.3% after 6 months. References: 10.1200/JCO.2024.42.16_suppl.9510

New DYP688 in Uveal melanoma with GNAQ Oncogenic mutations: 4

Phase 1 trial. NCT05415072. DYP688 is a first-in-class PMEL17-targeted antibody drug conjugate delivering a Gnaq/Gna11-specific inhibitor for metastatic uveal melanoma. It demonstrates potent antiproliferative activity and induces apoptosis in PMEL17-positive, GNAQ/11-mutant UVM cells. References: 10.1158/1538-8514.CANCERCHEM24-IA022

Changed Therapy in Uveal melanoma with GNA11 Oncogenic mutations: 4

Therapy changed: DarovasertibDYP688. Comments changed: Phase 2 study of neoadjuvant/adjuvant darovasertib for localized ocular melanoma, N=15, median tumor shrinkage was 11.2%/7.6%/22.7% after 1 month and 31.7%/11.9%/45.3% after 6 months.. References changed: 10.1200/JCO.2024.42.16_suppl.9510NCT05415072.

Changed Therapy in Solid tumours, Uveal melanoma with GNA11 Oncogenic mutations: 4

Therapy changed: Crizotinib + Darovasertib, Binimetinib + DarovasertibIDE196, Crizotinib + IDE196, Binimetinib + IDE196. Comments changed: Preclinical study. Combination of PKC inhibitor IDE196 with MET inhibitor crizotinib synergistically inhibited tumor cell proliferation in uveal melanoma cells, overcoming HGF-induced resistance to IDE196.. References changed: 10.1158/1538-7445.AM2021-1343NCT03947385.

Changed DYP688 in Uveal melanomaOncogenic mutations: 4

Biomarker changed: GNA11GNAQ. Comments changed: Phase 1 trial. NCT05415072. DYP688 is a first-in-class PMEL17-targeted antibody drug conjugate delivering a Gnaq/Gna11-specific inhibitor for metastatic uveal melanoma. It demonstrates potent antiproliferative activity and induces apoptosis in PMEL17-positive, GNAQ/11-mutant UVM cells.. References changed: 10.1158/1538-8514.CANCERCHEM24-IA022NCT05415072.

Changed Therapy in Solid tumours, Uveal melanoma with GNAQ Oncogenic mutations: 4

Therapy changed: Crizotinib + Darovasertib, Binimetinib + DarovasertibIDE196, Crizotinib + IDE196, Binimetinib + IDE196. Comments changed: Preclinical study. Combination of PKC inhibitor IDE196 with MET inhibitor crizotinib synergistically inhibited tumor cell proliferation in uveal melanoma cells, overcoming HGF-induced resistance to IDE196.. References changed: 10.1158/1538-7445.AM2021-1343NCT03947385.

Changed Therapy in Solid tumours with PRKCA Fusion: 4

Therapy changed: DarovasertibIDE196.

Changed Therapy in Solid tumours with PRKCB Fusion: 4

Therapy changed: DarovasertibIDE196.

Saturday, 22 March 2025 (Version: 20250322AU)

New Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF V600E: 2

Phase 3 BREAKWATER trial. NCT04607421. Encorafenib + cetuximab + mFOLFOX6 significantly improved ORR over SOC (60.9% vs 40.0%) in previously untreated BRAF V600E-mutant metastatic colorectal cancer, with a median duration of response of 13.9 months versus 11.1 months. References: 39863775

Sunday, 16 March 2025 (Version: 20250316AU)

New AZD9592 in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 4

Preclinical study. EGFR-cMET bispecific ADC showed antitumour activities in NSCLC and head and neck squamous cell carcinoma PDX models, with responses observed across a range of dose levels. Note activities are seen in with or without EGFR mutations in NSCLC as well as in head and neck squamous cell carcinoma. References: 10.1158/1538-7445.AM2023-5736

New Everolimus + Exemestane in Breast cancer with EIF4EBP1 Protein expression: 4

Exploratory biomarker study. NCT02444390. SAFIRTOR. p4EBP1 staining was associated with treatment outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane, with high-p4EBP1 associated with higher CBR (62% vs 40%) and longer PFS (9.2 vs 5.8 months). Positive staining was defined as p4EBP1 staining with Allred score >=6. References: 38182687

New Sotorasib + Tipifarnib in Solid tumours, Non-small cell lung cancer with KRAS G12C: 4

Preclinical study. Tipifarnib and sotorasib combination showed synergistic anticancer effects in lung adenocarcinoma cells by inhibiting proliferation and interfering with HRAS activation and RHEB/lamin farnesylation. References: 38278976

New Capivasertib + Docetaxel in Prostate cancer with PTEN Loss-of-function mutations: 4

Preclinical study. Capivasertib combined with docetaxel demonstrated enhanced anti-tumor activity in prostate cancer models by inhibiting AKT-mediated survival mechanisms, particularly in PTEN-null cells. References: 38396173

Saturday, 15 March 2025 (Version: 20250315AU)

New PF-9363 in Breast cancer with KAT6A Amplification, Overexpression: 4

Preclinical study. The selective KAT6A/KAT6B inhibitor demonstrated anti-tumor activity and growth suppression in KAT6-high ER+/luminal breast cancer models with or without ESR1 mutations associated with endocrine resistance. References: 37557181

New PF-9363 in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression, ESR1:D538, ESR1:Y537: 4

Preclinical study. The selective KAT6A/KAT6B inhibitor demonstrated anti-tumor activity and growth suppression in KAT6-high ER+/luminal breast cancer models with or without ESR1 mutations associated with endocrine resistance. References: 37557181

Friday, 7 March 2025 (Version: 20250307AU)

New Cabozantinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

Phase 2 trial. NCT02101736. N=19. Cabozantinib showed partial response in 42% of patients with neurofibromatosis type 1-related plexiform neurofibromas, with median change in tumor volume of 15.2%. References: 33442015

New Avutometinib + BI-3406 in Melanoma with NF1 Oncogenic mutations: 4

Preclinical study. Concurrent SOS1 and MEK inhibition suppressed signaling and growth of NF1-null melanoma, abrogated ERK activation, induced cell death, and suppressed tumor growth. References: 39488215

New Abemaciclib + LY3214996 in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 4

Preclinical study. Combined CDK4/6 and ERK1/2 inhibition enhanced antitumor activity in NF1-associated plexiform neurofibroma, with abemaciclib and LY3214996 synergizing to suppress MAPK activation and exhibiting enhanced antitumor activity in mouse models. References: 37406085

Changed Abemaciclib in Meningioma with NF2 : 3

Alterations changed: Oncogenic mutations.

Thursday, 6 March 2025 (Version: 20250306AU)

New ALTA-2618 in Breast cancer, Endometrial cancer with AKT1 E17K: 4

Preclinical study. The mutant-selective inhibitor of AKT1 E17K induced tumor regressions in multiple PDX models of breast and endometrial cancer models. References: 10.1158/1538-7445.AM2024-LB173

Sunday, 2 March 2025 (Version: 20250302AU)

New AZD1390 + GSK126 in Mesothelioma with BAP1 Loss of protein expression, Oncogenic mutations: 4

Preclinical study. Combination of EZH2 and ATM inhibition showed synergistic potential against BAP1-deficient mesothelioma in drug screen and xenograft experiments, indicating a potential novel treatment modality using BAP1 as a biomarker. References: 38519707

New Talazoparib in Myelodysplastic syndrome with SRSF2 P95H, Oncogenic mutations: 4

Preclinical study. Pathogenic SRSF2 activating mutations elevate protein poly-ADP-ribosylation levels, making mutant cells more vulnerable to PARP inhibitors in Srsf2 P95H knock-in murine hematopoietic cell and MLL-AF9 leukemia models. References: 38806724

New Cetuximab in Colorectal adenocarcinoma with ARID1A Oncogenic mutations: R2

Retrospective and correlative studies. ARID1A mutations confer intrinsic and acquired resistance to cetuximab treatment in colorectal cancer. Worse treatment outcome observed in patients with ARID1A mutations treated with cetuximab-containing therapies. References: 36117191

New Methotrexate in Acute lymphoblastic leukaemia with DHFR Amplification: R2

N=67, ALL patients, DHFR gene amplification (31%) correlated with p53 mutations (P < .001) is a mechanism of acquired resistance to methotrexate. References: 7605998

New Nivolumab + FLOX in Colorectal adenocarcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: R2

Randomized Phase 2. METIMMOX trial. NCT03388190. N=80. In microsatellite stable disease, no PFS advantage was observed with alternating FLOX + nivolumab over FLOX alone (both 9.2 months). References: 38664577

Monday, 24 February 2025 (Version: 20250224AU)

New Tuvusertib in Solid tumours with ARID1A Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with ATRX Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with BRCA1 Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with BRCA2 Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with DAXX Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New IMC-F106C in Melanoma with HLA-A2+PRAME HLA-A2:A*02:01 AND PRAME:Protein expression: 4

Phase 1 trial. NCT04262466. In 31 evaluable patients, IMC-F106C, a bispecific PRAME x CD3 ImmTAC showed activity in post-checkpoint cutaneous melanoma patients with 61% CBR and 13% ORR, enriched in PRAME-positive patients (immunohistochemistry H score>1). References: 10.1200/JCO.2024.42.16_suppl.9507

New Tuvusertib in Solid tumours with TP53 Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

Saturday, 22 February 2025 (Version: 20250222AU)

New Avutometinib + Defactinib in Non-small cell lung cancer with KRAS KRAS:Oncogenic mutations + CDH1:Protein expression + VIM:NOT Protein expresssion: 4

Preclinical study. Epithelial phenotype cells with KRAS-mutated non-small cell lung cancer show an enhanced apoptotic response to avutometinib and defactinib combination therapy through Bim upregulation, but not mesenchymal phenotypes. This study also suggests that EMT status could be a potential predictive biomarker. References: 38822146

New Larotrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, F589L, V573M, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib, Zurletrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, V573M, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib in Solid tumours with NTRK2 ETV6-NTRK2 fusion, V689M: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, F617L, G623E, G696A: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, G623E: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Zurletrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, G623E, G696A: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib, Zurletrectinib in Solid tumours with NTRK1 F589L, G595R, G667A, G667C, G667S: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK1 F589L, G595R, G667A, G667C, G667S, V573M: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK1 G595R, G667A, G667C, G667S: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib in Solid tumours with NTRK2 F633L, G639R, G709C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK3 F617L, G623R, G623E, G696A, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib in Solid tumours with NTRK3 F617L, G623R, G696A, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Zurletrectinib in Solid tumours with NTRK3 F617L, G623R, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK3 G623R, G623E, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

Changed Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600: 2

References changed: 37733309, 10.1200/JCO.2022.40.17_suppl.LBA200210.1056/NEJMoa2303815, 10.1200/JCO.2022.40.17_suppl.LBA2002.

Changed Vorasidenib in Low-grade gliomas with IDH1 Oncogenic mutation: 2

References changed: 3727251610.1056/NEJMoa2304194.

Changed Vorasidenib in Low-grade glioma with IDH2 Oncogenic mutation: 2

References changed: 3727251610.1056/NEJMoa2304194.

Friday, 21 February 2025 (Version: 20250221AU)

New SP2509 in Non-small cell lung cancer with DNMT3A Oncogenic mutations, Deletions, Truncating mutations, Loss-of-function mutations: 4

Preclinical study. KDM1A is a synthetic lethal partner of DNMT3A deletion in non-small cell lung cancer, reducing viability of DNMT3A-deficient cells through apoptosis. References: 38951697

New Isotretinoin + Navitoclax in Neuroblastoma with MYC Amplification: 4

Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models. References: 38942989

New Isotretinoin + Navitoclax in Neuroblastoma with MYCN Amplification: 4

Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models. References: 38942989

New Carboplatin + Etoposide, Cisplatin + Etoposide in Gastrointestinal neuroendocrine carcinoma with BRAF V600: R2

Retrospective analysis. N=229. BRAF alterations were not associated with response to platinum etoposide in gastrointestinal high-grade neuroendocrine neoplasms. References: 38909137

Monday, 17 February 2025 (Version: 20250217AU)

New Rucaparib + VE-821, Rucaparib + PF-477736, Rucaparib + MK-1775 in Ovarian cancer with BRCA1+BRCA2 NOT BRCA1:Oncogenic mutations and NOT BRCA2:Oncogenic mutations: 4

Preclinical study. ATR, CHK1, and WEE1 inhibitors induce homologous recombination repair deficiency in HR-proficient ovarian ascites models, sensitizing these cells to PARP inhibitors such as rucaparib. References: 38965423

Sunday, 16 February 2025 (Version: 20250216AU)

New Odronextamab in Follicular lymphoma with CD20 Protein expression: 3

Phase II ELM-2 trial. NCT03888105. N=128. Odronextamab achieved an ORR of 80% and CR rate of 73.4%, with a median DoR of 25.1 months, PFS of 20.7 months, and OS not reached in patients with relapsed or refractory follicular lymphoma. Note of level of CD20 expression was not associated with responses irrespective at baseline, CRs seen in no or low proportions of CD20-positive cells. References: 39147364

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 4

Retrospective analysis of the Phase 2 GOZILA trial. N=702. Putative germline BRCA1/2 mutation associated with better ORR (63.2% vs 16.2%) and PFS (HR 0.55) on platinum-containing chemotherapy. References: 39198618

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 4

Retrospective analysis of the Phase 2 GOZILA trial. N=702. Putative germline BRCA1/2 mutation associated with better ORR (63.2% vs 16.2%) and PFS (HR 0.55) on platinum-containing chemotherapy. References: 39198618

New Nivolumab in Hepatocellular carcinoma with CD274 Protein expression: 4

Phase 1/2. CheckMate 040 trial. N=234 (80 sorafenib-naive, 154 sorafenib-experienced). ORR was 20% and 14% in sorafenib-naive and sorafenib-experienced groups, respectively. Median OS were 26.6 months and 15.1 months, respectively. Higher ORR and extended OS were observed with baseline PD-L1 ≥1% vs <1%, more pronounced in the sorafenib-experienced group. References: 38151184

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA2 Reversion mutations: R2

Retrospective analysis of the Phase 2 GOZILA trial. N=702. Reversion mutation of BRCA2 gene was identified in two patients. References: 39198618

New Palbociclib, Ribociclib, Abemaciclib in Breast cancer with CDK4 Amplification: R2

Retrospective analysis. N=926. Focal CDK4 amplification, identified in ER+/HER2- metastatic breast cancers, represents a candidate acquired resistance mechanism to CDK4/6 inhibitors, with higher prevalence seen in populations pretreated with CDK4/6 inhibitors. References: 39090361

New Capivasertib in Gastric cancer with ARID1A Oncogenic mutation: 4

Preclinical study. AKT inhibition showed synthetic lethality in ARID1A-deficient gastric cancer cells via pyroptosis induction through Caspase-3/GSDME pathway activation. References: 39003371

New Trastuzumab in Extramammary Paget’s disease with ERBB2+PTEN ERBB2:Oncogenic mutations and PTEN:Loss of protein expression, ERBB2:Oncogenic mutations and PTEN:Loss-of-function mutations, ERBB2:Oncogenic mutations and PTEN:Oncogenic mutations, ERBB2:Oncogenic mutations and PTEN:Deletion: R2

Preclinical study. In PDX models, trastuzumab-resistant EMPD model showed PTEN loss as a resistance mechanism. References: 38987365

New Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA1 Oncogenic mutations: 4

Phase Ib. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response. References: 38971950

New Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA2 Oncogenic mutations: 4

Phase Ib. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response. References: 38971950

Friday, 14 February 2025 (Version: 20250214AU)

New BGB-B2033 in Hepatocellular carcinoma with GPC3 Protein expression: 4

References: NCT06427941

New BOS-342 in Hepatocellular carcinoma with GPC3 Protein expression: 4

References: ACTRN12623000798662

New MT-303 in Hepatocellular carcinoma with GPC3 Protein expression: 4

Preclinical study. MT-303, an LNP-formulated GPC3-specific CAR mRNA, demonstrated improved expression and anti-tumor activity in a hepatocellular carcinoma xenograft model (HepG2). 10.1136/jitc-2024-SITC2024.1125. References: NCT06478693

Changed Repotrectinib in Non-small cell lung cancer with ROS1 Fusion: 2

Comments changed: Not TGA approved. FDA approved. Phase 2 NCT03093116. TRIDENT-1 trial. N=296. Repotrectinib showed durable clinical activity in ROS1 TKI-naïve (ORR=88%) and -pretreated pts with or without BL CNS mets, including intracranial responses..

Monday, 10 February 2025 (Version: 20250210AU)

New MDNA11 in Solid tumours with Microsatellite Instability High: 4

Phase 1/2 ABILITY-1 trial. NCT05086692. N=30. MDNA11 showed single-agent activity in advanced solid tumors, with ORR of 7.7% and CBR of 19.2% in 26 evaluable patients, including one confirmed PR in a PDAC (MSI-H) patient. References: 10.1158/1538-7445.AM2024-CT259

Sunday, 9 February 2025 (Version: 20250209AU)

New VRN101099 in Breast cancer with ERBB2 Overexpression, Amplification: 4

Preclinical study. VRN101099, a brain-permeable HER2 kinase inhibitor, showed anti-tumor activity in HER2-positive cancer models with nanomolar potency. References: 10.1158/1538-7445.SABCS22-P1-11-03

Friday, 7 February 2025 (Version: 20250207AU)

Changed Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2 Overexpression

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. Trastuzumab deruxtecan demonstrated an overall response rate (ORR) of 34% (42/122) across two dose groups. The ORR was higher in the HER2 IHC 3+ population (47%, 30/64) but lower in the HER2 IHC 2+ with amplified group (5.6%, 1/18)..

Changed Zenocutuzumab in Solid tumours with NRG1 CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion: 2

Comments changed: Not TGA approved. FDA approved (accelerated). Phase 2 trial. NCT02912949. Updated results from phase 1/2 eNRGy trial. N=204. Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, with an ORR of 30% and median duration of response of 11.1 months; median PFS was 6.8 months. Response in PDAC was 42% in PDAC and 29% in NSCLC.Not TGA approved. FDA approved (accelerated). Updated results from phase 1/2 eNRGy trial. N=110. ORR 34% (27/84), including 42% in PDAC and 35% in NSCLC. Median DOR 9.1 months.. References changed: 39908431, 10.1200/JCO.2022.40.16_suppl.105.

Thursday, 6 February 2025 (Version: 20250206AU)

New Pemigatinib in Urothelial carcinoma with FGFR3 Fusion, R248C, S249C, S764fs*6, G370C, S371C, Y373C: 3

Phase 2. FIGHT-201. NCT02872714. N=260. Pemigatinib showed ORR of 17.8% and 23.3% in cohorts A-CD and A-ID respectively, with median DOR of 6.2 months, PFS of 4.0/4.3 months, and OS of 6.8/8.9 months in FGFR3-altered metastatic or surgically unresectable urothelial carcinoma. References: 37956738

New Erdafitinib in Urothelial carcinoma with FGFR3 S249C, Y373C, R248C, G370C, R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusion: 3

Phase 3. THOR trial. NCT03390504. N=351. Erdafitinib did not improve OS over pembrolizumab (10.9 vs 11.1 months) in anti-PD-L1-naive patients with metastatic urothelial cancer and selected FGFR alterations, but had a higher ORR (40% vs 21.6%) and longer PFS (4.4 vs 2.7 months). References: 37871702

New BBO-10203 in Breast cancer with ERBB2 Amplification, Overexpression: 4

Preclinical study. BBO-10203 demonstrates reduction of RAS-driven PI3Ka activity while maintaining normal glucose metabolism, exhibiting potent signaling pathway inhibition at low nanomolar concentrations and showing activity in PIK3CA-mutant and HER2-amplified human xenograft models. References: 10.1158/1538-7445.SABCS23-RF02-02

New Capmatinib in Non-small cell lung cancer with MET CD74-MET fusion: 4

Case report: Complete response in patient with metastatic NSCLC harboring CD47-MET fusion treated with capmatinib, achieving 18-month ongoing complete metabolic response after 3 prior lines of therapy. References: 38832711

New Olaparib in Breast cancer with BRCA1 Reversion mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Olaparib in Breast cancer with BRCA2 Reversion mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Pemigatinib in Urothelial carcinoma with FGFR3 V553M, V555L, V555M, M528I, N540S, N540K: R2

Phase 2. FIGHT-201. NCT02872714. N=260. Secondary acquired on-target resistance mutations detected at end of treatment in 6 patients. References: 37956738

New Olaparib in Breast cancer with PAXIP1 Oncogenic mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Olaparib in Breast cancer with RIF1 Oncogenic mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Olaparib in Breast cancer with TP53BP1 Oncogenic mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%.TGA approved. Not PBS reimbursed. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%..

Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed. Phase 3 trial. IMCgp100-202. NCT03070392. HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Median OS was significantly longer in tebentafusp group compared to control (21.6 versus 16.9 months). ORR was 14% (Control 5%).TGA approved. Not PBS reimbursed. Phase 3 trial. IMCgp100-202. NCT03070392. HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Median OS was significantly longer in tebentafusp group compared to control (21.6 versus 16.9 months). ORR was 14% (Control 5%)..

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification; Overexpression: 1B

Comments changed: TGA approved. FDA approved. Phase 2 trial NCT03248492 (N=184). DESTINY-Breast01: In patients with prior anti-HER2 therapies, the objective response rate (ORR) was 62%, with a median duration of response (DOR) of 14.8 months. The median overall survival (OS) was 29.1 months, with a median progression-free survival (PFS) of 19.4 months in patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab emtansine. HER2 positivity was defined as IHC 3+ or FISH positive.TGA approved. FDA approved. DESTINY-Breast01: In patients with prior anti-HER2 therapies, median DOR 14.8mo, PFS 16.4mo. HER2 positivity: defined as IHC 3+ or FISH positive.. References changed: 31825192, 38092229.

Tuesday, 4 February 2025 (Version: 20250204AU)

New BG-60366 in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation, T790M, activating mutations: 4

Based on Phase 1 inclusion criteria. Requires updates when publications become available. References: NCT06685718

New GSK_WRN4 in Solid tumours with Microsatellite Instability High: 4

Preclinical study. Novel WRN helicase inhibitors selectively targeted microsatellite unstable cancer cells by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage, with activities confirmed in immunotherapy-resistant organoids and patient-derived xenograft models. References: 38587317

Monday, 3 February 2025 (Version: 20250203AU)

New Patritumab deruxtecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861Q, G719: 3

Phase 1. U31402-A-U102 trial. N=102. In EGFR-mutated NSCLC patients who progressed after EGFR TKI and platinum-based chemotherapy, Patritumab deruxtecan showed confirmed ORR of 41% and median OS 16.2 months. References: 38369013

New Patritumab deruxtecan in Non-small cell lung cancer with ERBB3 Truncating mutations, Y789fs: R2

Phase 1. U31402-A-U102 trial. N=102. In EGFR-mutated NSCLC patients who progressed after EGFR TKI and platinum-based chemotherapy, Patritumab deruxtecan showed confirmed ORR of 41% and median OS 16.2 months. References: 38369013

New Patritumab deruxtecan in Non-small cell lung cancer with TOP1 L721R: R2

References: 38369013

Monday, 20 January 2025 (Version: 20250120AU)

New Avelumab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 4

Phase 2. MITO END-3 trial. NCT03503786. N=125. Compared with chemotherapy alone, avelumab efficacy varied by molecular profiling with favorable PFS in MSI-H and worst in MSS/TP53 mut in first-line endometrial cancer therapy. Significant interactions in PFS were observed in patients with ARID1A and PTEN mutations. References: 38704093

New Avelumab + Carboplatin + Paclitaxel in Endometrial cancer with ARID1A Oncogenic mutations: 4

Phase 2. MITO END-3 trial. NCT03503786. N=125. Compared with chemotherapy alone, avelumab efficacy varied by molecular profiling with favorable PFS in MSI-H and worst in MSS/TP53 mut in first-line endometrial cancer therapy. Significant interactions in PFS were observed in patients with ARID1A and PTEN mutations. References: 38704093

Sunday, 19 January 2025 (Version: 20250119AU)

New Camizestrant in Breast cancer with ESR1 E380Q, S463P, V422del, L536P, L536H, Y537C, Y537D, Y537N, Y537S, D538G: 3

Phase I. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44). References: 38729567

New Camizestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Phase I. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44). References: 38729567

New Durvalumab, Ipilimumab + Nivolumab, Nivolumab, Pembrolizumab in Colorectal cancer with POLD1 D402N, L606M: 3

Retrospective study. N=27. POLE/POLD1 proofreading-deficient metastatic CRC patients treated with immune checkpoint inhibitors showed ORR of 89%. Entry has been curated and tierd based on evidence of activity as demonstrated by the ORR, prolonged PFS, despite the absence of a prospective trial. References: 38777726

New Durvalumab, Ipilimumab + Nivolumab, Nivolumab, Pembrolizumab in Colorectal cancer with POLE P286R, S297Y, S297F, F367S, V411L, L424I, P436R, S459F, A456P: 3

Retrospective study. N=27. POLE/POLD1 proofreading-deficient metastatic CRC patients treated with immune checkpoint inhibitors showed ORR of 89%. Entry has been curated and tierd based on evidence of activity as demonstrated by the ORR, prolonged PFS, despite the absence of a prospective trial. References: 38777726

Changed Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 1

Comments changed: Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. The dual primary endpoint of OS at 24 months was 83% with dostarlimab and 59% with placebo, and was significantly improved over placebo with a hazard ratio of 0.69 at the updated analysis.Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. OS at 24 months was 83% with dostarlimab and 59% with placebo.. References changed: 36972026, 38866180.

Monday, 13 January 2025 (Version: 20250113AU)

New Neratinib + Trastuzumab emtansine in Breast cancer with ERBB2 Overexpression, Amplification: 3

Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + ado-trastuzumab emtansine achieved 33.3%-35.3% CNS ORR in HER2+ breast cancer brain metastases, with median OS of 20.9-30.2 months across three cohorts. References: 38977064

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations: 1

Comments changed: TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012.. References changed: 31562799, 39284381.

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations: 1

Comments changed: TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012.. References changed: 31562799, 39284381.

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with Homologous Recombination Deficiency Score High

Tier changed: 12. Comments changed: TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012: HRD was determined using myChoice HRD test with cut-off score of 42-100. Note: the HR proficient group also derives benefits from Niraparib.In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.Biomarker not approved by TGA. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012: HRD was determined using myChoice HRD test with cut-off score of 42-100. Note: the HR proficient group also derives benefits from Niraparib.. References changed: 31562799, 39284381.

Sunday, 12 January 2025 (Version: 20250112AU)

New Mirvetuximab soravtansine in Ovarian cancer with FOLR1 Protein expression, Overexpression: 3

Phase 2. PICCOLO trial. NCT05041257. N=79. Mirvetuximab soravtansine showed ORR of 51.9% and median DOR of 8.25 months in FRalpha-positive, third-line or later, recurrent platinum-sensitive ovarian cancer. Positive FRα expression was defined as 75% of cells with 2+ staining intensity, assessed using the VENTANA FOLR1 RxDx Assay on either a fresh/recent biopsy or archival tumour tissue. References: 39617145

New Ipilimumab + Nivolumab in Prostate cancer with Microsatellite Instability High: 3

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Mismatch repair Deficient: 3

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months. References: 39293514

New BMS-986365 in Prostate cancer with AR L702H, L702H and H875Y, L702H and T878A, L702H and W742C and T878A, T878A, W742C and T878A: 4

Phase 1. CC-94676-PCA-001. NCT04428788. In patients with progressive mCRPC, BMS-986365 showed activity in heavily pretreated patients and overcome resistance to current ARPIs, regardless of AR LBD mutation status. References: 39293515

New Ipilimumab + Nivolumab in Prostate cancer with BRCA2 Oncogenic mutation: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with CDK12 Oncogenic mutation: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Microsatellite Instability Tumour Mutational Burden:High and NOT Microsatellite instability:high: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Mismatch repair Tumour Mutational Burden:High and NOT Mismatch repair:deficient: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB. References: 39293514

Changed Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Cisplatin + Paclitaxel, Pembrolizumab + Carboplatin + Paclitaxel in Cervical cancer with CD274 Protein expression

Tier changed: 12. Comments changed: TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (2021-10-13). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup. Final analysis showed that the HR of OS results was significantly different in subgroups with or without bevacizumab: 77.1 months (pembrolizumab) versus 61.4 months (control) with bevacizumab, and 53.1 months (pembrolizumab) versus 33.7 months (control) without bevacizumab.Not TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (2021-10-13). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup.. References changed: 34534429, 39393777.

Changed Pembrolizumab in Colorectal adenocarcinoma with Mismatch repair Deficient: 1

Comments changed: PBS listed. TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. With an effective crossover rate of 62%, median OS was 77.5 v 36.7 months with chemotherapy (HR=0.73). MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.PBS listed. TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.. References changed: 33264544, 39631622, 10.1200/JCO.2020.38.18_suppl.LBA433264544, 10.1200/JCO.2020.38.18_suppl.LBA4.

Thursday, 9 January 2025 (Version: 20250109AU)

New Futibatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, E7090 in Cholangiocarcinoma with FGFR2 K642I: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Pemigatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 K660N: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550H, N550K, E566A, E566G, L618M, L618V: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550K, N550D, K660M: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Pemigatinib, Erdafitinib, E7090 in Cholangiocarcinoma with FGFR2 V563L, E566A, E566G, K642R: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 V565I: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Futibatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565F: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Infigratinib, Erdafitinib, Zoligratinib in Cholangiocarcinoma with FGFR2 K642I: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Infigratinib in Cholangiocarcinoma with FGFR2 K660N: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Infigratinib, Erdafitinib in Cholangiocarcinoma with FGFR2 N550H, N550K, E566A, E566G, L618M, L618V: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib,Infigratinib, Erdafitinib, E7090, Zoligratinib in Cholangiocarcinoma with FGFR2 N550K, N550D, K660M: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Infigratinib, Zoligratinib in Cholangiocarcinoma with FGFR2 V563L, E566A, E566G, K642R: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Derazantinib, Zoligratinib, AZD4547, Futibatinib in Cholangiocarcinoma with FGFR2 V565I: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Derazantinib, Zoligratinib, AZD4547, Futibatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 V565L: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550, L552F, V565, E566A, L618V, N653S: R2

Phase 1/2 FOENIX study. N=300. Futibatinib biomarker analysis detected treatment-emergent kinase mutation variants within 6 weeks of radiologic progression. CDKN2B alteration associated with reduced PFS in cholangiocarcinoma. References: 39672383

New Disitamab vedotin + Toripalimab in Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 3

Phase 1b/2 RC48-C014 trial. N=41. In locally advanced or metastatic urothelial carcinoma patients, disitamab vedotin + toripalimab showed confirmed ORR of 73%, median PFS of 9.3 months, and median OS of 33.1 months. The study was HER2-unselected, and responders were seen in HER2 1+/2+/3+ populations. References: 39662628

Changed Therapy in Solid tumours with FGFR1 Fusion: 4

Therapy changed: ZoligratinibDebio1347.

Changed Therapy in Solid tumours with FGFR1 Oncogenic mutations: 4

Therapy changed: ZoligratinibDebio1347.

Changed Therapy in Cholangiocarcinoma with FGFR2 Extracellular domain deletion, H167_N173del, L618F: 4

Therapy changed: ZoligratinibDebio1347. Comments changed: Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Zoligratinib experienced treatment response.Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Debio1347 experienced treatment response..

Changed Therapy in Solid tumours with FGFR2 Oncogenic mutations: 4

Therapy changed: ZoligratinibDebio1347.

Changed Therapy in Solid tumours with FGFR2 Truncating mutations, Rearrangements, FGFR2-E18, FGFR2-delE18, Exon 18 truncating mutations, FGFR2-BICC1 fusion, FGFR2-ATE1 fusion, FGFR2-E18-C2, FGFR2-E18-C3, FGFR2-E18-C4, Y674*, Y678*, L681fs*, P686*, S687fs*, S694*, C287R, Splice mutations, FGFR2-I17, FGFR2-E1-17AND Amplification: 4

Therapy changed: AZD4547, Pemigatinib, ZoligratinibAZD4547, Pemigatinib, Debio1347.

Changed Therapy in Solid tumours with FGFR3 Oncogenic mutations: 4

Therapy changed: ZoligratinibDebio1347.

Changed Therapy in Solid tumours with FGFR1 V561M: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347.

Changed Therapy in Cholangiocarcinoma with FGFR2 L618F: R2

Therapy changed: ZoligratinibDebio1347.

Changed Therapy in Solid tumours with FGFR2 V565I, N550K, V564M, V564F: R2

Therapy changed: Infigratinib, AZD4547, Zoligratinib, Dovitinib, PonatinibInfigratinib, AZD4547, Debio1347, Dovitinib, Ponatinib.

Changed Therapy in Cholangiocarcinoma with FGFR3 N540K, V555M, L608V: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347.

Changed Therapy in Solid tumours with FGFR3 V443, V555M: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347.

Tuesday, 24 December 2024 (Version: 20241224AU)

Friday, 6 December 2024 (Version: 20241206AU)

New Revumenib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Mixed phenotype acute leukaemia with KMT2A Rearrangement: 2

FDA approved. Not TGA approved. Phase 1/2. AUGMENT-101 trial. NCT04065399. N=94. Revumenib led to high remission rates with 23% of complete remission rate and 63% ORR in relapsed/refractory KMT2Ar acute leukaemia. References: 39121437

New Revumenib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia with KMT2A Rearrangement: 3

Phase 1. NCT04065399. Revumenib showed low frequency of grade 3 or higher treatment-related adverse events and 30% rate of complete remission or complete remission with partial haematologic recovery in patients with relapsed or refractory acute leukaemia. References: 36922593

New Zenocutuzumab in Solid tumours with NRG1 Fusion, CD74-NRG1 fusion, CLU-NRG1 fusion, ATP1B1-NRG1 fusion, SLC3A2-NRG1 fusion, APP-NRG1 fusion: 4

N=3. 2/3 patients with NRG1 fusion-positive metastatic cancer achieved rapid responses, including 2 with ATP1B1-NRG1 pancreatic cancer and 1 with CD74-NRG1 non-small cell lung cancer. References: 35135829

Changed Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression: 2

Comments changed: Not TGA approved. FDA approved (accelerated). Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months.Not TGA approved. FDA approved. Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months..

Changed Zenocutuzumab in Solid tumours with NRG1 CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion

Tier changed: 23. Comments changed: Not TGA approved. FDA approved (accelerated). Updated results from phase 1/2 eNRGy trial. N=110. ORR 34% (27/84), including 42% in PDAC and 35% in NSCLC. Median DOR 9.1 months..

Wednesday, 4 December 2024 (Version: 20241204AU)

Changed Belzutifan in Hemangioblastoma with VHL Oncogenic mutations (germline)

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved. Phase 2. NCT03401788. LITESPARK-004. Updated results. Belzutifan showed antitumor activity in VHL-associated renal cell carcinoma and other neoplasms. Updated results from CNS hemangioblastomas ORR 44%, DCR 90%, time 5.4 months, median PFS was not reached.TGA approved. Not PBS reimbursed. FDA approved. Phase 2. NCT03401788. LITESPARK-004. Updated results. Belzutifan showed antitumor activity in VHL-associated renal cell carcinoma and other neoplasms. Updated results from CNS hemangioblastomas ORR 44%, DCR 90%, time 5.4 months, median PFS was not reached..

Changed Belzutifan in Pancreatic neuroendocrine tumour, Hemangioblastoma with VHL Oncogenic mutations (germline)

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas.TGA approved. Not PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas..

Changed Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline)

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%.TGA approved. Not PBS listed. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%..

Tuesday, 3 December 2024 (Version: 20241203AU)

Monday, 2 December 2024 (Version: 20241202AU)

New Trastuzumab in Breast cancer with ERBB2 p95 expression: R2

Preclinical study. HER2-overexpressing breast cancer cells expressing p95HER2 were resistant to trastuzumab, but sensitive to lapatinib, with significant growth inhibition and tumor regression in xenograft models. References: 17440164

New Lapatinib in Breast cancer with ERBB2 p95 expression: 4

Preclinical study. HER2-overexpressing breast cancer cells expressing p95HER2 were resistant to trastuzumab, but sensitive to lapatinib, with significant growth inhibition and tumor regression in xenograft models. References: 17440164

Friday, 22 November 2024 (Version: 20241122AU)

New BWA-522 in Prostate cancer with AR AR-FL; AR-V7: 4

Preclinical study. Orally bioavailable PROTAC degrader targeting N-terminal domain of androgen receptor inducing degradation of both AR-FL and AR-V7 in prostate cancer cell line and rowth inhibition in LNCaP xenograft model. References: 37556600

New CC-94676 in Prostate cancer with AR Wildtype, Amplifications, Oncogenic mutations: 4

Phase 1. NCT04428788. in metastatic castration-resistant prostate cancer patients, CC-94676 34% of patients achieved PSA30 across all dose levels. References: 10.1200/JCO.2024.42.4_suppl.134

New AZD4547, Pemigatinib, Debio1347 in Solid tumours with FGFR2 Truncating mutations, Rearrangements, FGFR2-E18, FGFR2-delE18, Exon 18 truncating mutations, FGFR2-BICC1 fusion, FGFR2-ATE1 fusion, FGFR2-E18-C2, FGFR2-E18-C3, FGFR2-E18-C4, Y674*, Y678*, L681fs*, P686*, S687fs*, S694*, C287R, Splice mutations, FGFR2-I17, FGFR2-E1-17AND Amplification: 4

Preclinical study. Truncated FGFR2 identified as actionable oncogene in multiple cancers, including rearrangements, partial amplifications, and nonsense/frameshift mutations, with FGFR2-E18 truncation being a single-driver alteration. References: 35948633

Changed Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months..

Changed Bemarituzumab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with FGFR2 : 4

Alterations changed: Overexpression, FGFR2b:Overexpression, FGFR2-IIIb:Overexpression.

Changed Bemarituzumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with FGFR2 : 4

Alterations changed: Overexpression, FGFR2b:Overexpression, FGFR2-IIIb:Overexpression, amplification.

Thursday, 21 November 2024 (Version: 20241121AU)

Wednesday, 20 November 2024 (Version: 20241120AU)

Monday, 18 November 2024 (Version: 20241118AU)

Thursday, 14 November 2024 (Version: 20241114AU)

Wednesday, 13 November 2024 (Version: 20241113AU)

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with BRCA1 Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with BRCA2 Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with PALB2 Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with RAD51C Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with RAD51D Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

Tuesday, 5 November 2024 (Version: 20241105AU)

New Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3

Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma. References: 37490286

New Zolbetuximab, Zolbetuximab + Pembrolizumab in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: R2

Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma. References: 37490286

Monday, 4 November 2024 (Version: 20241104AU)

New Gefitinib in Non-small cell lung cancer with CRKL Amplification: R2

Preclinical study. CRKL amplification induces transformation and EGFR inhibitor resistance, activates SOS1-RAS-RAF-ERK and SRC-C3G-RAP1 pathways in NSCLC lines. References: 22586683

New Atezolizumab in Hepatocellular carcinoma with CRKL Amplification, Overexpression: R2

Preclinical study. CRKL overexpression attenuates anti-PD-1 efficacy by mobilizing tumor-associated neutrophils in HCC. Blocking CRKL/β-catenin/VEGF alpha and CXCL1 axis using bevacizumab or lenvatinib overcomes anti-PD-1 resistance. References: 38403027

Saturday, 2 November 2024 (Version: 20241102AU)

Friday, 1 November 2024 (Version: 20241101AU)

New Trastuzumab duocarmazine in Breast cancer with ERBB2 Overexpression, Amplification: 2

Phase 3. TULIP. NCT03262935. N=437. Trastuzumab duocarmazine improved PFS over physician's choice (7.0 vs 4.9 months) with HR of 0.64 in patients with HER2-positive advanced or metastatic breast cancer who progressed during/after 2 or more HER2-targeted therapies or after T-DM1. References: 39442070

Thursday, 31 October 2024 (Version: 20241031AU)

Sunday, 27 October 2024 (Version: 20241027AU)

Saturday, 26 October 2024 (Version: 20241026AU)

Thursday, 24 October 2024 (Version: 20241024AU)

New Palbociclib in Peritoneal mucinous carcinomatosis with GNAS Oncogenic mutations: 3

Phase 2. N=16. Palbociclib showed clinical activity in GNAS-mutant peritoneal mucinous carcinomatosis. SD was observed in 50% of evaluable patients after 12 months. Median OS was not reached at a median follow-up of 17.6 months. References: 39413348

Saturday, 19 October 2024 (Version: 20241019AU)

New Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18+ERBB2 CLDN18:Protein expression AND NOT ERBB2:Overexpression; CLDN18:Protein expression AND NOT ERBB2:Amplification: 2

Phase 3. SPOTLIGHT. NCT03504397. N=565. Addition of Zolbetuximab significantly prolonged both PFS and OS in previously untreated patients with Claudin 18.2 positive and HER2 negative gastric and gastroesophageal cancers (median PFS 10.6 vs 8.7 months, median OS 18.2 vs 15.5 months). CLDN18 positive was defined as moderate-to-strong IHC staining in >= 75% of tumour cells. References: 37068504, 10.1200/JCO.2023.41.3_suppl.LBA292

New Zolbetuximab + CAPOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18+ERBB2 CLDN18:Protein expression AND NOT ERBB2:Overexpression; CLDN18:Protein expression AND NOT ERBB2:Amplification: 2

Not TGA approved. FDA approved. Phase 3 GLOW trial. NCT03653507. N=507. Zolbetuximab + CAPOX improved PFS over placebo (8.2 vs 6.8 months) and OS 14.4 vs 12.2 months in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. Claudin18.2 expression was defined as >= 75% of tumor cells with moderate-to-strong membranous staining on immunohistochemistry. References: 37524953

Removed Zolbetuximab + FOLFOX in Gastric cancer; Gastroesophageal junction adenocarcinoma with CLDN18 alterations Protein expression: Tier 2

Sunday, 13 October 2024 (Version: 20241013AU)

New Inavolisib in Breast cancer with ESR1+ERBB2+PIK3CA ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and PIK3CA:Oncogenic mutations: 2

Not TGA approved. FDA approved. Phase 3. INAVO120 trial. NCT04191499. N=325. Inavolisib + palbociclib + fulvestrant significantly improved PFS2 (24.0 vs 15.1 months) and Time to first chemotherapy (not estimable vs 15.0 months) over placebo in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer. References: 10.1200/JCO.2024.42.16_suppl.1003

Thursday, 10 October 2024 (Version: 20241010AU)

Changed IK-930 in Epithelioid haemangioendothelioma with WWTR1 : 4

Alterations changed: WWTR1-CAMTA1 fusion (TAZ-CAMTA1 fusion), fusionWWTR1-CAMTA1 fusion, fusion.

Tuesday, 8 October 2024 (Version: 20241008AU)

New Ribociclib + Letrozole, Ribociclib + Anastrozole, Ribociclib + Tamoxifen, Letrozole, Ribociclib + Letrozole + Goserelin, Ribociclib + Anastrozole + Goserelin, Ribociclib + Tamoxifen + Goserelin, Letrozole, Fulvestrant in Breast cancer with ESR1 D351Y, E380Q, S463P, M528I, L536H, L536P, Y537C, Y537S, Y537D, D538G: R2

Combined biomarker analysis of MONALEESA-2, -3, and -7 trials. Higher prevalences of ESR1 gene alterations was seen in D538, Y537, E380, L536 (with potential candidates at D351, M528). References: 39313156

New Ribociclib in Breast cancer with RB1 Oncogenic mutation: R2

Pooled analysis of the MONALEESA study. Significantly more alterations in the RB1 and SPEN genes at the point of progression compared to baseline in patients from the ribociclib arm. References: 39313156

New Ribociclib in Breast cancer with SPEN Oncogenic mutation: R2

Pooled analysis of the MONALEESA study. Significantly more alterations in the RB1 and SPEN genes at the point of progression compared to baseline in patients from the ribociclib arm. References: 39313156

Saturday, 5 October 2024 (Version: 20241005AU)

New Gilteritinib in Acute myeloid leukaemia with ABL1 BCR-ABL1 Fusion: R2

Secondary FLT3-F691L gatekeeper mutations or BCR-ABL1 fusions were identified at progression to Gilteritinib. References: 31088841

New Gilteritinib in Acute myeloid leukaemia with FLT3 F691L: R2

Secondary FLT3-F691L gatekeeper mutations or BCR-ABL1 fusions were identified at progression to Gilteritinib. References: 31088841

Friday, 4 October 2024 (Version: 20241004AU)

New AMG 193 in Solid tumours with MTAP Deletion, Loss of protein expression: 3

Phase 1. NCT05094336. In patients with MTAP-deleted solid tumors, the MTA-cooperative PRMT5 inhibitor AMG 193 showed ORR of 21% across dose ranges of 800 mg o.d., 1200 mg o.d., or 600 mg b.i.d.. Responses were seen in cholangiocarcinoma, oesophageal carcinoma, gallbladder adenocarcinoma, melanoma, non-small cell lung carcinoma, pancreatic adenocarcinoma, renal cell carcinoma, Sertoli-Leydig cell tumor. References: 39293516

New ZN-1041 in Breast cancer with ERBB2 Overexpression, amplification: 4

Phase 1, ZN-A-1041-101-US (NCT05593094). N=10. 1 pt achieved confirmed PR at 400 mg BID dose for >15 months. References: 10.1200/JCO.2023.41.16_suppl.1041

New Trametinib + Hydroxychloroquine, Trametinib + Palbociclib in Pancreatic adenocarcinoma with KRAS Oncogenic mutation: 4

Retrospective multicentric cohort study, AIO AIO-TF/PAK-0123, N=34, trametinib + hydroxychloroquine (THCQ) or trametinib + palbociclib (TP) did not show clinical benefit in advanced metastatic pancreatic cancer with KRAS mutations or MAPK/CDKN2A/B alterations. References: 39352477

New MYTX-011 in Non-small cell lung cancer with MET Protein expression: 4

Phase 1. MYTX-011 showed improved payload delivery to c-MET-expressing tumor cells, with increased cytotoxicity and efficacy in NSCLC xenograft models. References: 38684230

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+KRAS BRAF:V600E AND KRAS:Oncogenic mutations, BRAF:V600E AND KRAS:G12, BRAF:V600E AND KRAS:G13, BRAF:V600E AND KRAS:Q61, BRAF:V600E AND KRAS:K117, BRAF:V600E AND KRAS:A146: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+MAP2K1 BRAF:V600E AND MAP2K1:Oncogenic mutations, BRAF:V600E AND MAP2K1:F53, BRAF:V600E AND MAP2K1:K57: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+MET BRAF:V600E AND MET:amplification: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+NRAS BRAF:V600E AND NRAS:Oncogenic mutations, BRAF:V600E AND NRAS:G12, BRAF:V600E AND NRAS:G13, BRAF:V600E AND NRAS:Q61: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

Monday, 30 September 2024 (Version: 20240930AU)

New Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 4

References: 33632773

New Afatinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, G719A, G719S, S768I, L861R, L861Q, A763_Y764insFQEA: 4

References: 33632773

New Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861R, L861Q, A763_Y764insFQEA, P772_H773insGNP, A767_V769dup: 4

References: 33632773

New Mobocertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861R, L861Q, A763_Y764insFQEA, P772_H773insGNP, A767_V769dup, T790M, G719A, G719S, S768I, Exon 20 insertion, N771_H773dup, S768_D770dup: 4

Preclinical study. Mobocertinib (TAK-788) demonstrated potent inhibition of EGFR exon 20 insertion mutants in non-small cell lung cancer with selectivity over wild-type EGFR. References: 33632773

New Erlotinib, Gefitinib, Osimertinib, Mobocertinib in Non-small cell lung cancer with EGFR L858R and T790M and C797S: R2

References: 33632773

New Afatinib in Non-small cell lung cancer with EGFR T790M, Exon 20 insertion, P772_H773insGNP, A767_V769dup, N771_H773dup, S768_D770dup: R2

Intermediate sensitivities for Afatinib: S768I. References: 33632773

New Osimertinib in Non-small cell lung cancer with EGFR T790M, G719A, G719S, S768I, Exon 20 insertion, N771_H773dup, S768_D770dup: R2

References: 33632773

New Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR T790M, G719A, G719S, S768I, L861R, L861Q, A763_Y764insFQEA, Exon 20 insertion, P772_H773insGNP, A767_V769dup, N771_H773dup, S768_D770dup: R2

Intermediate sensitivities for Erlotinib: G719A, L861R, L861Q, A763_Y764insFQEA. References: 33632773

Wednesday, 25 September 2024 (Version: 20240925AU)

New GSK2256098 in Meningioma with NF2 Oncogenic mutations: 3

Phase 2 Alliance A071401 trial. NCT02523014. N=36. GSK2256098 showed activity in NF2-mutated meningiomas, meeting PFS6 endpoint with rates of 83% (grade 1) and 33% (grade 2/3), and one partial response was observed. References: 36288512

New Lirafugratinib in Cholangiocarcinoma with FGFR2 FGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M: 4

References: 37270847

New Infigratinib in Cholangiocarcinoma with FGFR2 K310R, M537I, K641N, K659M: 4

References: 37270847

New Futibatinib in Cholangiocarcinoma with FGFR2 K310R, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M: 4

References: 37270847

New Erdafitinib in Cholangiocarcinoma with FGFR2 K310R, M537I, N549H, V564I, E565A, L617V, K641N, K659M: 4

References: 37270847

New Pemigatinib in Cholangiocarcinoma with FGFR2 K310R, M537I, N549H, V564I, K641N, K659M: 4

References: 37270847

New RMC-9805 in Pancreatic adenocarcinoma, Non-small cell lung cancer with KRAS G12D: 4

Preclinical study. RMC-9805, a mutant-selective covalent oral KRASG12D inhibitor, induced apoptosis and tumor regression in KRASG12D models, with objective responses seen in pancreatic and non-small cell lung cancer PDX and CDX models. References: 10.1158/1538-7445.AM2023-526

New IAG933 in Solid tumours with NF2 Oncogenic mutations: 4

Preclinical study. The direct disruptor of YAP-TEAD interface showed anti-tumor activity in Hippo-driven mesothelioma xenografts and extended to larger tumor indications, including lung, pancreatic, and colorectal cancer, with durable responses. References: 38565920

New Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer with FGFR1 Amplification: R2

Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers. References: 35304457

New Futibatinib in Cholangiocarcinoma with FGFR2 V564F, V564L: R2

References: 37270847

New Infigratinib in Cholangiocarcinoma with FGFR2 V564F, V564L, N549D, N549H, N549K, E565A, V564I, L617V: R2

References: 37270847

New Pemigatinib in Cholangiocarcinoma with FGFR2 V564F, V564L, N549D, N549K, E565A, L617V: R2

References: 37270847

New Erdafitinib in Cholangiocarcinoma with FGFR2 V564F, V564L, N549K, N549D: R2

References: 37270847

New Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer with MET Amplification: R2

Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers. References: 35304457

New Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer with RET Y806C, G810C, G801S: R2

Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers. References: 35304457

Changed Lapatinib + Trastuzumab in Colorectal adenocarcinoma with ERBB2 Amplification: 3

Comments changed: Phase 2 HERACLES trial. N=27. Trastuzumab + lapatinib achieved ORR of 30% (8/27) with 1 complete response and 7 partial responses in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer..

Changed Therapy in Cholangiocarcinoma with FGFR2 Fusion: 3

Therapy changed: LirafugratinibRLY-4008.

Changed Therapy in Cholangiocarcinoma with FGFR2 Fusion, C382R, R678H, H167_N173del, C383R, W290C: 3

Therapy changed: LirafugratinibRLY-4008.

Changed Lenvatinib in Non-small cell lung cancer with RET Fusions: 3

Comments changed: Phase 2 trial. NCT01877083. N=25. Lenvatinib demonstrated an ORR of 16% and a median PFS of 7.3 months in patients with RET fusion-positive lung adenocarcinoma.Single-arm phase 2. ORR 16%. PFS 7.3mo.

Changed Therapy in Solid tumours with FGFR2 Fusion: 4

Therapy changed: LirafugratinibRLY-4008.

Changed MRTX1133 with KRAS G12D: 4

Cancer type(s) changed: Pancreatic adenocarcinoma, Colorectal adenocarcinoma

Changed Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer: R2

Biomarker changed: BRAFRET. Alterations changed: D594N, Oncogenic mutationsY806C, G810C, G801S. Comments changed: Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers..

Changed Pictilisib + Paclitaxel in Breast cancer with PIK3CA Oncogenic mutations: R2

Comments changed: Phase 2 PEGGY trial. NCT01740336. N=183. Pictilisib did not improve PFS over placebo (8.2 vs 7.8 months) or response rate in combination with paclitaxel for hormone receptor-positive, HER2-negative breast cancer.PEGGY. No PFS improvement over placebo. Similar ORR.

Changed MK2206 in Colorectal adenocarcinoma with PIK3CA Oncogenic mutations: R2

Comments changed: Phase 2 trial. NCT01802320. Biomarker-enriched, previously treated metastatic colorectal cancer patients received MK2206, an oral AKT inhibitor, with no radiographic responses, median PFS of 1.8 months, and median OS of 6.8 months. ORR was 0% in patients with PIK3CA mutations (0/2).ORR 0%.

Changed Everolimus in Glioblastoma with PTEN Deletion, Loss of protein expression: R2

Comments changed: Preclinical study. Glioblastoma orthotopic xenograft test panel. PTEN loss did not predict response to everolimus with only 1 of 7 PTEN-disrupted lines showing sensitivity..

Changed MK2206 in Colorectal adenocarcinoma with PTEN Loss of protein expression: R2

Comments changed: Phase 2 trial. NCT01802320. Biomarker-enriched, previously treated metastatic colorectal cancer patients received MK2206, an oral AKT inhibitor, with no radiographic responses, median PFS of 1.8 months, and median OS of 6.8 months. ORR was 0% in PTEN loss patients (0/9).ORR 0%.

Changed Vismodegib in Medulloblastoma with SMO D473, E518: R2

Comments changed: Preclinical study. GDC-0449-resistant SMO mutants identified with D473H and E518 mutations.

Changed Selinexor in Chronic myelogenous leukaemia, Acute lymphoblastic leukaemia, Acute promyelocytic leukaemia with XPO1 C528S: R2

Comments changed: Preclinical study. Heterozygous C528S mutation in XPO1 confers similar resistance to selinexor as homozygous substitution, demonstrating a single dominant mutation is sufficient for SINE resistance..

Sunday, 22 September 2024 (Version: 20240922AU)

New SGN-PDL1V in Solid tumours, Head and neck squamous cell carcinoma, Non-small cell lung carcinoma with CD274 Protein expression: 4

Phase 1. SGNPDL1V-001. NCT05208762. N=55. Single agent SGN-PDL1V showed ORR of 27% (13% confirmed) and median duration of confirmed responses of 7.9 months. Responses were seen across PD-L1 levels. References: 10.1016/j.annonc.2024.08.674

New YL201 in Solid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer with CD276 Protein expression: 3

Phase 1. NCT06057922 and NCT05434234. In patients with advanced solid tumors, single agent YL201 aided ORR was 74% in SCLC, 46% in NPC, and 32% in NSCLC (wild type especially in adenocarinoma and LELC); at ≥2.0 mg/kg dose level. References: 10.1016/j.annonc.2024.08.672

New SHR-A1904 in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3

Phase 1. NCT04877717. SHR-A1904 showed anti-tumor activity in 73 patients with GC/GEJC, with ORR of 56% at 6.0 mg/kg (DCR 89%). Claudin 18.2 positivity in ≥ 1% of cells. References: 10.1016/j.annonc.2024.08.676

New DS-9606a in Solid tumours, Testicular cancer, Gastric cancer, Non-small cell lung cancer with CLDN6 Protein expression: 4

Phase 1. NCT05394675. N=40. In Phase 1 DS-9606a trial, confirmed responses were seen in in germ-cell tumours, gastric cancer, and non-small cell lung cancer. CLDN6 expression is not required as part of the eligibiity for entry. References: 10.1016/j.annonc.2024.08.677

New BNT211 in Solid tumours, Testicular cancer, Ovarian cancer with CLDN6 Protein expression: 4

Phase 1. BNT211-01 trial. NCT04503278. N=59. Updated results showed ORR of 38% and DCR of 69%. TRAE in 88% of patients, 64% Grade 3 or more with 39% SAE. References: 10.1016/j.annonc.2024.08.678

New Furmonertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 2

Phase 3. FURLONG trial. NCT03787992. N=358. Median PFS was significantly longer in patients treated with furmonertinib versus gefitinib (20.8 vs 11.1 months) as first-line therapy in EGFR mutation-positive NSCLC. References: 35662408

New Zalontamab Brengitecan in Solid tumours with EGFR+ERBB3 EGFR:Protein expression AND ERBB3:Protein expression: 3

Phase 1. NCT05194982. N=195. BL-B01D1, showed objective response rate of 34% in patients with locally advanced or metastatic solid tumours. No relationship was found between H-scores and EGFR or HER3 and response. References: 38823410

New Zalontamab Brengitecan in Urothelial carcinoma with EGFR+ERBB3 EGFR:Protein expression AND ERBB3:Protein expression: 3

Phase 1b/2 trial. NCT05785039. N=32. Locally advanced or metastatic urothelial carcinoma. ORR was 44% (10/23), 35% confirmed. DCR was 91%, mPFS was 5.5 months at dose of 2.2 mg/kg. References: 10.1016/j.annonc.2024.08.2044

New ASP3082 in Solid tumours with KRAS G12D: 3

Phase 1. NCT05382559. N=98. ASP3082 monotherapy showed response in patients with advanced pancreatic cancer with ORR 5 of 27 (19%), colorectal cancer, and non-small cell lung cancer 3 of 13 responders. ORR was 33% at 300mg. References: 10.1016/j.annonc.2024.08.675

New RLY-2608 in Breast cancer with PIK3CA H1047R, E453K, E542K: 4

Phase 1. NCT05216432. RLY-2608. Objective responses was seen in 2 patients with advanced hormone receptor-positive breast cancer and PIK3CA mutations. References: 37916956

New STX-478 in Solid tumours with PIK3CA H1047R, H1047L, M1043, E545K, G1049R, Kinase domain mutation, Helical domain mutation: 3

Phase 1/2 trial. NCT05768139. N=61. In advanced solid tumor patients STX-478, monotherapy showed an ORR of 21% in 43 evaluable patients. DCR was 70%. References: 10.1016/j.annonc.2024.08.2266

New Puxitatug samrotecan in Solid tumours with VCTN1 Protein expression: 3

Phase 1/2a. BLUESTAR. NCT05123482. N=46. AZD8205 showed preliminary efficacy with 21% in heavily pre-treated patients with advanced and metastatic solid tumours. CtDNA reductions were seen across tumour types. References: 10.1016/j.annonc.2024.08.673

New CFT1946 in Solid tumours, Melanoma, Pancreatic adenocarcinoma with BRAF V600E, V600K, V600R: 4

Phase 1/2. NCT05668585, N=25, BRAF V600 mutant solid tumors. 1 unconfirmed partial response and 7/14 pts with stable disease or better in patients with pretreated BRAF V600 inhibitors. 8 of 11 with melanoma demonstrated tumour reduction. References: 10.1016/j.annonc.2024.08.679

New PRT3789 in Solid tumours with SMARCA4 Oncogenic mutation: 4

Phase 1. NCT05639751. Across dose levels, responses were see in PRT3789 including 3 partial responses and prolonged stable disease in patients with advanced solid tumors with SMARCA4 mutations. References: 10.1016/j.annonc.2024.08.670

Wednesday, 11 September 2024 (Version: 20240911AU)

New VS-4718 in Mesothelioma with NF2 Loss-of-function mutations, deletion: 4

Preclinical study. Nf2 deficiency predicts sensitivity toFAK inhibitor in cell lines and MPM xenograft models, particularly in ALDH-positive cancer stem cells. References: 24848258

Changed Imlunestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Comments changed: Phase Ia/Ib EMBER study. NCT04188548. N=262. Imlunestrant showed manageable safety profile and preliminary antitumor activity in ER+/HER2- advanced breast cancer, with median PFS of 7.2 months (monotherapy) and up to 19.2 months (in combination with targeted therapy)..

Monday, 9 September 2024 (Version: 20240909AU)

New Imlunestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

References: 39241211

Sunday, 8 September 2024 (Version: 20240908AU)

New Selumetinib in Low-grade gliomas, Paediatric low grade gliomas with BRAF KIAA1549-BRAF fusion, V600E: 3

Phase 2. NCT01089101. N=50. Selumetinib achieved sustained partial response in 36% (9/25) of patients with BRAF-aberrant pilocytic astrocytoma and 40% (10/25) of patients with NF1-associated paediatric low-grade glioma. References: 31151904

New Mirdametinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

NF106. Phase II trial. N=19. NCT02096471. ORR 42%; CBR 95% with significant durable decreases in pain ratings in patients with NF1-related plexiform neurofibromas. References: 33507822

Changed Selumetinib with NF1 Oncogenic mutations (germline)

Cancer type(s) changed: Low-grade gliomas, Paediatric low grade gliomas, Type 1 neurofibromatosis Tier changed: 12. Comments changed: TGA approved. PBS reimbursed for paediatric patients with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Phase 2. NCT01089101. N=50. Selumetinib achieved sustained partial response in 36% (9/25) of patients with BRAF-aberrant pilocytic astrocytoma and 40% (10/25) of patients with NF1-associated paediatric low-grade glioma.Not TGA approved.

Changed Therapy in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

Therapy changed: FCN-159Mirdametinib. Comments changed: Phase 1/2. NCT04954001. N=65. In pediatric patients with neurofibromatosis type 1-related plexiform neurofibromas. ORR was 42% in 19 patients with evaluable response. Median DOR could not be evaluated.NF106. Phase II trial. ORR 42%; CBR 95%.. References changed: 10.1200/JCO.2023.41.16_suppl.1002333507822.

Saturday, 7 September 2024 (Version: 20240907AU)

New Luveltamab tazevibulin in Ovarian cancer with FOLR1 Protein expression: 3

Phase 1. Dose expansion cohort of STRO-002-GM1. NCT03748186. N=44. Luveltamab tazevibulin showed activity (ORR 12 of 32, 38%) in recurrent epithelial ovarian cancer with FolRα expression as low as TPS>25%. References: 10.1200/JCO.2023.41.16_suppl.5508

Changed Dostarlimab in Endometrial cancer with Microsatellite Instability High

Tier changed: 12.

Changed Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High

Tier changed: 12.

Changed Pembrolizumab in Endometrial cancer with Microsatellite Instability High

Tier changed: 12.

Friday, 6 September 2024 (Version: 20240906AU)

New PRT7732 in Solid tumours with SMARCA4 Oncogenic mutation: 4

Preclinical study. PRT7732 induces synthetic lethality in SMARCA4-deficient cancers with low nanomolar DC50 values and significant tumor growth inhibition in xenograft models. References: 10.1158/1538-7445.AM2024-4503

Wednesday, 4 September 2024 (Version: 20240904AU)

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification

Tier changed: 1B.

Tuesday, 3 September 2024 (Version: 20240903AU)

Changed Dabrafenib + Trametinib in Non-small cell lung cancer with BRAF V600E: 1B

Comments changed: TGA approved. Not PBS reimbursed. Phase 2 trial. NCT01336634. N=36. Dabrafenib + trametinib showed an ORR of 64% (23/36) with a median follow-up of 15.9 months in previously untreated BRAFV600E-mutant metastatic NSCLC.. References changed: 2891901129072975.

Monday, 2 September 2024 (Version: 20240902AU)

New ERX-315 in Breast cancer with ESR1 D538G, Y537S, D538G, Y537S: 4

Preclinical study. ERX-315 induced endoplasmic reticulum stress leading to cancer cell death in mutant estrogen receptor alpha -driven breast cancer cell lines. References: 10.1158/1538-7445.SABCS23-PO3-26-11

Thursday, 29 August 2024 (Version: 20240829AU)

New Tazemetostat in Mesothelioma with BAP1 Loss of protein expression, Oncogenic mutations: 3

Phase 2. NCT02860286. N=74. Tazemetostat showed DCR of 54% at week 12 in patients with BAP1-inactivated pleural mesothelioma, meeting the primary endpoint of the study. Two PR were seen. References: 35588752

New Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2 Overexpression: 3

Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. Trastuzumab deruxtecan demonstrated an overall response rate (ORR) of 34% (42/122) across two dose groups. The ORR was higher in the HER2 IHC 3+ population (47%, 30/64) but lower in the HER2 IHC 2+ with amplified group (5.6%, 1/18). References: 39116902

New A947 in Solid tumours with SMARCA4 Oncogenic mutation: 4

Preclinical study. Synthetic lethality and cell growth inhibition were observed in SMARCA4 mutant cancer through selective SMARCA2 degradation in in vitro models. References: 36357397

New PRT3789 in Solid tumours with SMARCA4 Oncogenic mutation: 4

Phase I. NCT05639751. PRT3789 selectively targets SMARCA4-deficient cells with anti-tumor activity and synergistic effects with therapies. References: 10.1158/1535-7163.TARG-23-B113

New Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2 Protein expression AND Amplification AND NOT Overexpression: R2

Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. Trastuzumab deruxtecan demonstrated an overall response rate (ORR) of 34% (42/122) across two dose groups. The ORR was higher in the HER2 IHC 3+ population (47%, 30/64) but lower in the HER2 IHC 2+ with amplified group (5.6%, 1/18). References: 39116902

New Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2+KRAS ERBB2:Overexpression AND KRAS:Oncogenic mutation, ERBB2:Protein expression AND KRAS:Oncogenic mutation: R2

Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. In the post-hoc analysis, RAS mutations identified by ctDNA (either clonal or subclonal) were associated with a lower response rate (13%) compared to RAS wild-type. References: 39116902

Tuesday, 27 August 2024 (Version: 20240827AU)

New Osimertinib + Tepotinib in Non-small cell lung cancer with EGFR+MET EGFR:Oncogenic mutations and MET:amplification: 3

Phase 2. INSIGHT-2. NCT03940703. N=128. ORR was 50% in EGFR-mutated NSCLC patients with MET amplification treated with Tepotinib and Osimertinib. Median DOR was 8.5 months. MET amplification was determined by FISH on tissue biopsy (gene copy number >=5 or MET-to-CEP7 ratio >=2) or liquid NGS (plasma gene copy number of >=2.3). References: 39089305

New Osimertinib + Tepotinib in Non-small cell lung cancer with EGFR+MET EGFR:Oncogenic mutation AND MET:amplification AND MET:D1228, EGFR:Oncogenic mutation AND MET:amplification AND MET:D1230: R2

Phase 2. INSIGHT-2. NCT03940703. N=128. Treatment emergent resistance following Tepotinib + Osimertinib treatment. References: 39089305

New Osimertinib + Tepotinib in Non-small cell lung cancer with EGFR+MET+ALK EGFR:Oncogenic mutation AND MET:amplification AND EML4-ALK fusion: R2

Phase 2. INSIGHT-2. NCT03940703. N=128. No response was seen in patients with co-mutations in BRAF, KRAS, and ALK fusions. References: 39089305

New Osimertinib + Tepotinib in Non-small cell lung cancer with EGFR+MET+BRAF EGFR:Oncogenic mutation AND MET:amplification AND BRAF:Oncogenic mutation: R2

Phase 2. INSIGHT-2. NCT03940703. N=128. No response was seen in patients with co-mutations in BRAF, KRAS, and ALK fusions. References: 39089305

New Osimertinib + Tepotinib in Non-small cell lung cancer with EGFR+MET+KRAS EGFR:Oncogenic mutation AND MET:amplification AND KRAS:Oncogenic mutation: R2

Phase 2. INSIGHT-2. NCT03940703. N=128. No response was seen in patients with co-mutations in BRAF, KRAS, and ALK fusions. References: 39089305

Friday, 23 August 2024 (Version: 20240823AU)

New Everolimus in Non-small cell lung cancer with STK11 Oncogenic mutations: 4

References: 34422335

New BI 764532 in Small-cell lung cancer, Neuroendocrine carcinoma with DLL3 Protein expression: 3

Phase 1. NCT04429087. First-in-human dose-escalation trial of BI 764532 in DLL3-positive SCLC and NEC. N=90. At the target dose, ORR was 33% in SCLC and 22% in NEC. References: 10.1200/JCO.2023.41.16_suppl.8502

Monday, 19 August 2024 (Version: 20240819AU)

New Talazoparib in Neuroblastoma with BARD1 Oncogenic mutations (germline): 4

Case report. Complete response to talazoparib + irinotecan in a child with refractory neuroblastoma and germline BARD1 mutation and achieving sustained disease control for 32 months. References: 39141861

Thursday, 8 August 2024 (Version: 20240808AU)

Changed Fulvestrant + Alpelisib in Breast cancer with PIK3CA+FGFR2 : 3

Alterations changed: PIK3CA:Oncogenic mutation AND FGFR2:AlterationPIK3CA:Oncogenic mutation AND FGFR1:Alteration.

Tuesday, 6 August 2024 (Version: 20240806AU)

Wednesday, 31 July 2024 (Version: 20240731AU)

New Naporfenib in Solid tumours with BRAF Exon 12 deletion: 4

Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors. References: 37656784

New Sorafenib in Solid tumours with BRAF L485_P490delinsF, L485_P490delinsY: 4

Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors. References: 37656784

New Encorafenib, Dabrafenib in Solid tumours with BRAF N486_P490del, V487_P492delinsA: 4

Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors. References: 37656784

New OBI-999 in Solid Tumours with Globo H Expression: 4

Phase 1. NCT04084366. References: 36701651

New Encorafenib, Dabrafenib in Solid tumours with BRAF L485_P490delinsF, L485_P490delinsY, L485delinsFS: R2

Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors. References: 37656784

Friday, 19 July 2024 (Version: 20240719AU)

New Pemigatinib in Glioblastoma with FGFR1 K656E: 3

Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months. References: 38710951

New Pemigatinib in Cholangiocarcinoma with FGFR2 Fusion, FGFR2-BICC1 fusion, FGFR2-RBM20 fusion, FGFR2-MRVI1 fusion, FGFR2-CROCC fusion, FGFR2-KIAA1598 fusion, FGFR2 1291_Y308del, FGFR2 W290C, FGFR2 Y375C, FGFR2 C382R: 3

Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months. References: 38710951

New Pemigatinib in Cervical cancer, Endometrial cancer with FGFR2 C382R: 3

Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months. References: 38710951

New Pemigatinib in Urothelial carcinoma, Glioblastoma, Cervical cancer, Endometrial cancer with FGFR3 FGFR3-TACC3 fusion, FGFR3 Y373C: 3

Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months. References: 38710951

New Pemigatinib in Cervical cancer, Endometrial cancer with FGFR3 Fusion, FGFR3-TACC3 fusion: 3

Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months. References: 38710951

New Pemigatinib in Cholangiocarcinoma with BRAF V600E, L525R: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Breast cancer, Endometrial cancer, Solitary fibrous tumour with FGFR1 N546K, N546D: R2

Phase 2. FIGHT-207 basket. NCT03822117. De novo primary resistance mutations prior to Pemigatinib without response. References: 38710951

New Pemigatinib in Pancreatic adenocarcinoma with FGFR1 V559L, V559M, N546K: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Cancer of unknown primary with FGFR2 E565A, N549K: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Cholangiocarcinoma with FGFR2 N549K, N549D, N549H, N549F, M537I, V564I, V564F, V564L, L617V, K641R, K569M: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Breast cancer, Endometrial cancer, Solitary fibrous tumour with FGFR2 N549K, V395D, R664W, K505E: R2

Phase 2. FIGHT-207 basket. NCT03822117. De novo primary resistance mutations prior to Pemigatinib without response. References: 38710951

New Pemigatinib in Gastric cancer with FGFR2 V564F: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Non-small cell lung cancer with FGFR3 V555M, V555L: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Cancer of unknown primary with KRAS A59T, G13D: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Cancer of unknown primary with NRAS Q61H, G13D, G12D: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

New Pemigatinib in Cholangiocarcinoma with NRAS Q61R, Q61K, G13V, G13D, G12S: R2

Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib. References: 38710951

Changed Trastuzumab deruxtecan in Biliary tract cancer with ERBB2 Overexpression: 3

References changed: 37870536, 37870536, 10.1200/JCO.2023.41.17_suppl.LBA3000.

Changed Trastuzumab deruxtecan in Cervical cancer, Endometrial cancer, Ovarian cancer, Bladder cancer, Solid tumours except Pancreatic adenocarcinoma, Biliary tract cancers with ERBB2 Overexpression, Protein expression: 3

References changed: 37870536, 10.1200/JCO.2023.41.17_suppl.LBA3000.

Changed Trastuzumab deruxtecan in Pancreatic adenocarcinoma with ERBB2 Overexpression, Protein expression: R2

References changed: 37870536, 10.1200/JCO.2023.41.17_suppl.LBA3000.

Wednesday, 17 July 2024 (Version: 20240717AU)

New ARV-766 in Prostate cancer with AR Ligand-binding domain mutation: 3

Phase 1/2 study. NCT05067140. N=103. In castration-resistant prostate cancer patients with AR LBD mutations resulted in PSA50 of 50%. References: 10.1200/JCO.2024.42.16_suppl.5011

New Tarlatamab in Prostate small cell carcinoma with DLL3 Protein expression: 3

Phase 1b study. NCT04702737. N=38 (evaluable patients with de novo or treatment-emergent neuroendocrine prostate cancer). ORR was 22% (4/38) and median PFS was 3.8 months in the DLL3+ subgroup. No response was seen in 20 evaluable patients. DLL3 positivity was defined by IHC in >= 1% of patients. References: 10.1200/JCO.2024.42.16_suppl.5012

Changed FG-M108 + Nab-paclitaxel + Gemcitabine in Pancreatic adenocarcinoma with CLDN18 Overexpression, Protein expression, Low protein expression: 4

References changed: 10.1200/JCO.2024.42.16_suppl.4049.

Monday, 15 July 2024 (Version: 20240715AU)

New FG-M108 + Nab-paclitaxel + Gemcitabine in Pancreatic adenocarcinoma with CLDN18 Overexpression, Protein expression, Low protein expression: 4

Phase 1b study. NCT04894825. Activities were observed in PDAC patients with positive Claudin 18.2 expression receiving FG-M108 + nab-paclitaxel and gemcitabine in CLDN18.2 expression. Immunohistochemistry (IHC) showed at least 1+ in at least 10% of cells. References:

Thursday, 4 July 2024 (Version: 20240704AU)

New APG-2449 in Non-small cell lung cancer with ALK Fusion: 3

Phase 1/2. APG-2449. NCT03917043. N=144. ORR was 68% in ROS1 TKI-naive and 796% in ALK TKI-naive patients. In 2G ALK inhibitor-resistant patients, ORR was 41%, mPFS was 11.9 months. Encouraging intracranial ORR was seen. References: 10.1200/JCO.2024.42.16_suppl.3124

New BAY 2927088 in Non-small cell lung cancer with ERBB2 Oncogenic mutations: 3

Phase I/II SOHO-01 study. NCT05099172. N=34. BAY 2927088 led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months. References: 10.1200/JCO.2024.42.17_suppl.LBA8598

New APG-2449 in Solid tumours, Non-small cell lung cancer, Anaplastic large cell lymphoma with ALK EML4-ALK fusion, NPM-ALK fusion, C1156Y, L1196M, I1171T, F1197M, G1269A, S1206Y, R1275Q, F1174L: 4

Preclinical study. APG-2449 is a ALK/ROS1/FAK inhibitor. References: 35820889

New APG-2449 in Non-small cell lung cancer with ROS1 CD74-ROS1 fusion, L2026M: 4

Preclinical study. APG-2449 is a ALK/ROS1/FAK inhibitor. References: 35820889

New APG-2449 in Non-small cell lung cancer with ALK G1202R: R2

Preclinical study. APG-2449 is a ALK/ROS1/FAK inhibitor. References: 35820889

Changed 9MW2821 in Solid Tumours, Urothelial carcinoma, Cervical Cancer, Oesophageal cancer, Triple-negative breast cancerProtein expression: 3

Biomarker changed: NECTIN4NETCIN4.

Changed Therapy in Solid tumours with CD274 Amplification: 4

Therapy changed: Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, immune checkpoint blockade,PD-L1-targetingAnti-PD-1 monoclonal antibody, immune checkpoint blockade,PD-L1-targeting.

Changed Durvalumab in Endometrial cancer with Microsatellite Instability : R2

Alterations changed: Stable, NOT High.

Sunday, 30 June 2024 (Version: 20240630AU)

Sunday, 23 June 2024 (Version: 20240623AU)

New Brigatinib in Vestibular schwannoma, Non-vestibular schwannoma, Meningioma, Ependymoma, Type 2 neurofibromatosis with NF2 Oncogenic mutations (germline): 2

Phase 2. INTUITT-NF2. NCT04374305. N=40. Radiographic response in 10% of target tumors and 23% of all tumors from Brigatinib monotherapy. Benefit meningiomas and nonvestibular schwannomas, and hearing improvement in 35% of eligible ears. References: 38904277

Saturday, 22 June 2024 (Version: 20240622AU)

New SHR-A1811 in Breast cancer, Solid Tumours with ERBB2 Amplification, Overexpression, Protein expression, Low protein expression, Oncogenic mutations: 3

Phase 1. NCT04446260. N=307. SHR-A1811 showed activity with an objective response rate of 60%in heavily pretreated HER2-expressing or mutated advanced solid tumors. Response rates were 76% in 118 HER2-positive breast cancer, 60% for HER2 low-expressing, and 46% in 98 other solid cancers. References: 38900984

Changed Fam-trastuzumab deruxtecan-nxki in Non-small cell lung cancer with ERBB2 Protein expression AND NOT Oncogenic mutations, Overexpression AND NOT Oncogenic mutations: 3

References changed: 38547891.

Thursday, 20 June 2024 (Version: 20240620AU)

Tuesday, 18 June 2024 (Version: 20240618AU)

New Atezolizumab in Endometrial cancer, Neuroendocrine carcinoma, Non-small-cell lung cancer, Pancreatic cancer, Sarcoma, Gastrooesophageal carcinoma, Cervical cancer, Cancer of unknown primary, Prostate cancer, Non-melanoma skin cancer with Tumour Mutational Burden High: 3

Phase 2. TAPISTRY trial. NCT04589845. N=150. Atezolizumab showed ORR of 23% (TMB ≥16 mut/Mb) and 20% (TMB ≥13 mut/Mb), with median PFS of 2.8 months and 2.7 months, respectively, in patients with TMB-high solid tumors. TMB was assessed by Foundation One CDx. Tumour types with n>=4 and ORR >=20 are listed. The correlation with MSI-H, dMMR, and PD-L1 status were not reported. References: 10.1200/JCO.2024.42.17_suppl.LBA2509

New Atezolizumab in Breast cancer, Hepatobiliary cancers, Solid Tumours with Tumour Mutational Burden High: 4

Phase 2. TAPISTRY trial. NCT04589845. N=150. Atezolizumab showed ORR of 23% (TMB ≥16 mut/Mb) and 20% (TMB ≥13 mut/Mb), with median PFS of 2.8 months and 2.7 months, respectively, in patients with TMB-high solid tumors. TMB was assessed by Foundation One CDx. Tumour types with n>=4 are identifed; no objective responses were seen in breast and hepatobiliary cancers. References: 10.1200/JCO.2024.42.17_suppl.LBA2509

Monday, 17 June 2024 (Version: 20240617AU)

New NST-628 in Solid tumours with NRAS Oncogenic mutations: 4

Based on Phase 1 inclusion criteria. References: NCT06326411

Changed NST-628 with BRAF Class II mutations, Class III mutations: 4

Cancer type(s) changed: Solid tumours

Sunday, 9 June 2024 (Version: 20240609AU)

New Nivolumab + Ipilimumab in Colorectal adenocarcinoma with Microsatellite Instability High: 2

Phase 3. CheckMate 8HW. NCT04008030. N=303. Nivolumab + ipilimumab showed superior PFS over chemotherapy (HR 0.21; median not reached vs 5.9 months) in MSI-H/dMMR metastatic colorectal cancer patients, including improvement in PFS after the subsequent therapy. References: 10.1200/JCO.2024.42.16_suppl.3503

New Nivolumab + Ipilimumab in Colorectal adenocarcinoma with Mismatch repair Deficient: 2

Phase 3. CheckMate 8HW. NCT04008030. N=303. Nivolumab + ipilimumab showed superior PFS over chemotherapy (HR 0.21; median not reached vs 5.9 months) in MSI-H/dMMR metastatic colorectal cancer patients, including improvement in PFS after the subsequent therapy. References: 10.1200/JCO.2024.42.16_suppl.3503

New Taletrectinib in Non-small cell lung cancer with ROS1 Fusions, CD74-ROS1 fusion, SDC4-ROS1 fusion, EZR-ROS1 fusion, SLC34A2-ROS1 fusion, TPM3-ROS1 fusion, CD83-ROS1 fusion, LRIG1-ROS1 fusion, MYH9-ROS1 fusion, SDC4-ROS1 fusion, KLHDC2-ROS1 fusion. SLC34A2-ROS1 fusion, TPR-ROS1 fusion, G2101A, G2032R, L2026M, S1986F: 2

Phase 2. TRUST-I study. NCT04395677. N=173. Taletrectinib showed high ORR (91% in TKI-naive, 52% in crizotinib-pretreated). PFS was NR (TKI-naive) and 7.6 months (crizotinib-pretreated.). References: 10.1200/JCO.2024.42.16_suppl.8520

New Olaparib in Breast cancer with BRCA1 Oncogenic mutations AND NOT Oncogenic mutations (germline): 3

Phase 2 TBCRC-048. N=54. Olaparib showed ORR of 75% in gPALB2-mutated MBC (Cohort 1a) and 36.7% in sBRCA-mutated MBC (Cohort 2a), with median PFS of 9.6 months and 5.6 months, respectively. References: 10.1200/JCO.2024.42.16_suppl.1021

New Olaparib in Breast cancer with BRCA2 Oncogenic mutations AND NOT Oncogenic mutations (germline): 3

Phase 2 TBCRC-048. N=54. Olaparib showed ORR of 75% in gPALB2-mutated MBC (Cohort 1a) and 36.7% in sBRCA-mutated MBC (Cohort 2a), with median PFS of 9.6 months and 5.6 months, respectively. References: 10.1200/JCO.2024.42.16_suppl.1021

New Abemaciclib in Meningioma with CDKN2A Oncogenic mutation: 3

Phase 2 Alliance A071401 trial. N=36. Abemaciclib improved PFS at 6 months of 54% in patients with recurrent or progressive grade 2/3 meningiomas and NF2 mutations or CDK pathway alterations, meeting primary endpoint. No objective responses observed. References: 10.1200/JCO.2024.42.16_suppl.2001

New Letetresgene autoleucel in Synovial sarcoma, Myxoid liposarcoma, Round cell liposarcoma with CTAG1B Protein expression, Overexpression: 3

Phase 2. IGNYTE-ESO substudy 2. NCT03967223. N=45. ORR was 40% (18/45) in patients with NY-ESO-1-expressing synovial sarcoma or myxoid/round cell liposarcoma. Median duration of response of 10.6 months. References: 10.1200/JCO.2024.42.16_suppl.2500

New Glecirasib + JAB-3312 in Non-small cell lung cancer with KRAS G12C: 3

Phase 1/2a study, NCT05288205, In front-line NSCLC patients with KRAS G12C mutations (n=102), treated with Glecirasib + JAB-3312, ORR was 65% in all front-line NSCLC patients (77% in the 800mg + 2mg group). Median PFS 12.2 months. References: 10.1200/JCO.2024.42.16_suppl.3008

New Olomorasib in Non-small cell lung cancer with KRAS G12C: 3

Phase 1/2 LOXO-RAS-20001. N=157. Olomorasib showed activity across KRAS G12C-mutant NSCLC. ORR was 39% with median PFS of 6 months. References: 10.1200/JCO.2024.42.16_suppl.3007

New Vebreltinib in Glioblastoma with MET PTPRZ1-MET fusion: 3

Phase 2/3. FUGEN, NCT06105619. Vebreltinib improved OS (6.3 vs 3.4 months) and PFS (1.9 vs 1.1 months) over chemotherapy in previously treated, PTPRZ1-MET fusion positive secondary glioblastoma, IDH-mutant glioblastoma patients. References: 10.1200/JCO.2024.42.16_suppl.2003

New 9MW2821 in Solid Tumours, Urothelial carcinoma, Cervical Cancer, Oesophageal cancer, Triple-negative breast cancer with NETCIN4 Protein expression: 3

Phase 1/2a, NCT05216965, n=260, 9MW2821, a nectin-4 antibody-drug conjugate, showed ORR of 35% and DCR of 78% at 1.25 mg/kg or above. Median PFS ranging from 3.7 to 8.8 months across different tumor types. Objective response rates were 62, 38, 30, and 44% for urothelial, cervical, oesophageal, and triple negative breast cancers respectively. References: 10.1200/JCO.2024.42.16_suppl.3013

New Abemaciclib in Meningioma with NF2 Oncogenic mutation: 3

Phase 2 Alliance A071401 trial. N=36. Abemaciclib improved PFS at 6 months of 54% in patients with recurrent or progressive grade 2/3 meningiomas and NF2 mutations or CDK pathway alterations, meeting primary endpoint. No objective responses observed. References: 10.1200/JCO.2024.42.16_suppl.2001

New Olaparib in Breast cancer with PALB2 Oncogenic mutations (germline): 3

Phase 2 TBCRC-048. N=54. Olaparib showed ORR of 75% in gPALB2-mutated MBC (Cohort 1a) and 36.7% in sBRCA-mutated MBC (Cohort 2a), with median PFS of 9.6 months and 5.6 months, respectively. References: 10.1200/JCO.2024.42.16_suppl.1021

New KSQ-4279 + Olaparib in Ovarian cancer with BRCA1 Oncogenic mutation: 4

Phase 1 trial. NCT05240898. N=64. KSQ-4279, a first-in-class USP1 inhibitor, showed acceptable in combination with olaparib or carboplatin in patients with advanced solid tumours and deleterious HRR mutations; disease control rate at 16 weeks was 28%, 40%, and 29% respectively. References: 10.1200/JCO.2024.42.16_suppl.3005

New KSQ-4279 + Olaparib in Ovarian cancer with BRCA2 Oncogenic mutation: 4

Phase 1 trial. NCT05240898. N=64. KSQ-4279, a first-in-class USP1 inhibitor, showed acceptable in combination with olaparib or carboplatin in patients with advanced solid tumours and deleterious HRR mutations; disease control rate at 16 weeks was 28%, 40%, and 29% respectively. References: 10.1200/JCO.2024.42.16_suppl.3005

New M94140 in Colorectal cancer with CEACAM5 Protein expression: 4

Phase 1 trial. NCT05464030. N=40. M9140 demonstrated activity with manageable safety profile with ORR of 10% (4 PR) and median PFS of 6.7 months in heavily pretreated CRC patients. Note CEACAM5 expression is not required for enrollment into the trial. References: 10.1200/JCO.2024.42.16_suppl.3000

New Telisotuzumab Vedotin in Non-small cell lung cancer with EGFR+MET MET:overexpression AND NOT EGFR:oncogenic mutation: 4

Phase 2. LUMINOSITY. NCT03539536.. N=161. Telisotuzumab vedotin showed ORR of 34.6% in c-Met high and 22.9% in EGFR wildtype, c-Met intermediate NSCLC patients, with a median DOR of 9.0 months and 7.2 months respectively. cMET status was determined by IHC intense staining with a cut-off at 50% (high) or 25% (intermediate) of cells. References: 10.1200/JCO.2024.42.16_suppl.103

New PF-07248144 in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 4

Phase 1. NCT04606446. N=78. Durable response of PF-07248144 was seen in heavily pretreated ER+ HER2- metastatic breast cancer. ORR was 11% as monotherapy and 30% in combination with fulvestrant. Median PFS was 10.7 months. References: 38822758, 10.1200/JCO.2024.42.16_suppl.3006

New Sacituzumab tirumotecan in Triple-negative breast cancer with ESR1+ERBB2 NOT ESR1:protein expression and NOT ERBB2:amplified, NOT ESR1:protein expression and NOT ERBB2:overexpression: 4

Phase 3. OptiTROP-Breast01. NCT05347134. N=263. Sacituzumab tirumotecan significantly improved PFS over chemotherapy (5.7 vs 2.3 months) and OS (HR 0.53, median OS not reached vs 9.4 months). ORR 43.8% in advanced TNBC. References: 10.1200/JCO.2024.42.16_suppl.104

New MRG004A in Solid tumours with F3 Protein expression: 4

Phase I/II study. N=63. MRG004A showed antitumor activity in heavily pretreated patients with solid tumors, including pancreatic cancer (ORR 33%, DCR 83%) at 2mg/kg. References: 10.1200/JCO.2024.42.16_suppl.3002

New Olomorasib in Solid tumours with KRAS G12C: 4

Phase 1/2 LOXO-RAS-20001. N=157. Olomorasib showed activity across KRAS G12C-mutant solid tumours. ORR was 9% in CRC and 40% in non-CRC tumors. with median PFS of 4-9 months. References: 10.1200/JCO.2024.42.16_suppl.3007

New Navtemadlin in Glioblastoma with MDM2+TP53+IDH1 MDM2:Amplification AND NOT TP53:Oncogenic mutations AND NOT IDH1:Oncogenic mutations: 4

Preclinical study: Navtemadlin showed activities in TP53 wildtype GBM flank PDX models, but CNS penetration was limited by P-gp. Intratumoral levels required for efficacy varied is dependent on MDM2 amplification status. References: 10.1200/JCO.2024.42.16_suppl.2012

New Niraparib + Radiotherapy in Glioblastoma with MGMT Unmethylated: 4

References: 10.1200/JCO.2024.42.16_suppl.2002

New KSQ-4279 + Olaparib in Ovarian cancer with RAD51D Oncogenic mutation: 4

Phase 1 trial. NCT05240898. N=64. KSQ-4279, a first-in-class USP1 inhibitor, showed acceptable in combination with olaparib or carboplatin in patients with advanced solid tumours and deleterious HRR mutations; disease control rate at 16 weeks was 28%, 40%, and 29% respectively. References: 10.1200/JCO.2024.42.16_suppl.3005

New ABBV-706 in Small-cell lung cancer, Neuroendocrine carcinoma, Solid tumour with SEZ6 Protein expression: 4

Phase 1, first-in-human study of ABBV-706. N=49. ORR was 21% (7 PRs), with 40% in SCLC and 6% in neoruendocrine neoplasms. CBR was 91%. SEZ6 expression is not required for enrollment. References: 10.1200/JCO.2024.42.16_suppl.3001

New Panitumumab + FOLFOX in Colorectal adenocarcinoma with ALK Oncogenic mutation: R2

Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months). References: 10.1200/JCO.2024.42.16_suppl.3507

New Panitumumab + FOLFOX in Colorectal adenocarcinoma with BRAF Oncogenic mutation: R2

Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months). References: 10.1200/JCO.2024.42.16_suppl.3507

New Panitumumab + FOLFOX in Colorectal adenocarcinoma with EGFR Oncogenic mutation: R2

Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months). References: 10.1200/JCO.2024.42.16_suppl.3507

New Panitumumab + FOLFOX in Colorectal adenocarcinoma with ERBB3 Oncogenic mutation: R2

Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months). References: 10.1200/JCO.2024.42.16_suppl.3507

New Panitumumab + FOLFOX in Colorectal adenocarcinoma with KRAS Oncogenic mutation: R2

Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months). References: 10.1200/JCO.2024.42.16_suppl.3507

New Panitumumab + FOLFOX in Colorectal adenocarcinoma with NRAS Oncogenic mutation: R2

Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months). References: 10.1200/JCO.2024.42.16_suppl.3507

New Crizotinib in Non-small cell lung cancer with ROS1 G2101A, G2032R, L2026M, S1986F: R2

Phase 2. TRUST-I study. NCT04395677. N=173. Taletrectinib showed high ORR (91% in TKI-naive, 52% in crizotinib-pretreated). PFS was NR (TKI-naive) and 7.6 months (crizotinib-pretreated.). References: 38822758, 10.1200/JCO.2024.42.16_suppl.8520

Changed FOLFOX + Panitumumab in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

References changed: 37071094, 10.1200/JCO.2022.40.17_suppl.LBA1.

Changed Trastuzumab Deruxtecan in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 : 3

Alterations changed: Protein expression and NOT Amplification, Low protein expression and NOT Amplification.

Changed Therapy in Solid tumours with NTRK1 Fusion: 4

Therapy changed: TaletrectinibDS-6051b.

Changed Therapy in Solid tumours with NTRK2 Fusion: 4

Therapy changed: TaletrectinibDS-6051b.

Changed Therapy in Solid tumours with NTRK3 Fusion: 4

Therapy changed: TaletrectinibDS-6051b.

Changed Therapy in Non-small cell lung cancer with ROS1 Fusions; G2032R: 4

Therapy changed: TaletrectinibDS-6051b.

Monday, 27 May 2024 (Version: 20240527AU)

New NST-628 in Solid tumour with BRAF Class II mutations, Class III mutations: 4

Preclinical study. NST-628, a pan-RAF-MEK molecular glue, demonstrated broad activity in cell line and PDX models with MAPK pathway alterations. References: 38588399

New NST-628 in Solid tumour with KRAS Oncogenic mutations: 4

Preclinical study. NST-628, a pan-RAF-MEK molecular glue, demonstrated broad activity in cell line and PDX models with MAPK pathway alterations. References: 38588399

New NST-628 in Solid tumour with NRAS Q61R, Q61: 4

Preclinical study. NST-628, a pan-RAF-MEK molecular glue, demonstrated broad activity in cell line and PDX models with MAPK pathway alterations. References: 38588399

Sunday, 26 May 2024 (Version: 20240526AU)

Sunday, 19 May 2024 (Version: 20240519AU)

New Amivantamab + Carboplatin + Pemetrexed, Amivantamab + Carboplatin + Pemetrexed + Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 1B

Phase 3. NCT04988295. MARIPOSA-2: Amivantamab and chemotherapy with or without lazertinib prolonged PFS for EGFR-mutant advanced NSCLC patients after progression on osimeterinib, versus chemotherapy alone (median PFS by investigator, 8.3, 8.3, and 4.2 months). ORR was higher (64% and 63% vs 36%). References: 37879444

Changed Enzalutamide + Talazoparib in Prostate cancer with BRCA1 : 2

Alterations changed: Oncogenic mutations.

Changed Enzalutamide + Talazoparib in Prostate cancer with BRCA2 : 2

Alterations changed: Oncogenic mutations.

Wednesday, 15 May 2024 (Version: 20240515AU)

New Fam-trastuzumab deruxtecan-nxki in Non-small cell lung cancer with ERBB2 Protein expression AND NOT Oncogenic mutations, Overexpression AND NOT Oncogenic mutations: 3

Phase 2. NCT03505710. DESTINY-Lung01. Confirmed ORR 27% (N=49, Cohort 1) and 34 (N=41, Cohort 1A) respectively. References:

New TAS-102 + Olaparib, TAS-102 + Talazoparib in Colorectal adenocarcinoma, Pancreatic adenocarcinoma with TP53 Oncogenic mutations: 4

Cell line study. In vitro study showed that trifluorothymidine and PARP inhibitor demonstrated synergistic activity against p53-mutant colorectal and pancreatic cancers with higher anti-neoplastic activity in p53-mutant models. References: 38387463

Wednesday, 8 May 2024 (Version: 20240508AU)

New Fam-trastuzumab deruxtecan-nxki in Solid tumours with ERBB2 S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, A775_G776insYVMA, L755S, P780_Y781insGSP, T862A, V842I: 3

Phase 2. DESTINY-PanTumor01. NCT04639219. N=102. Trastuzumab deruxtecan showed anti-tumour activity and durable responses in heavily pretreated patients across multiple tumour types with activating HER2 mutations. The ORR was 29%. References: 38710187

Changed Fam-trastuzumab deruxtecan-nxki in Non-small cell lung cancer with ERBB2 : 2

Alterations changed: S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, P780_Y781insGSP, G778_S779insLPS, Exon 20 insertion, Exon 20 mutationS310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, G778_P780dup, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation.

Wednesday, 1 May 2024 (Version: 20240501AU)

New Everolimus in Glioblastoma with PTEN Deletion, Loss of protein expression: R2

References: 18559622

Monday, 29 April 2024 (Version: 20240429AU)

Sunday, 28 April 2024 (Version: 20240428AU)

New Enfortumab Vedotin in Urothelial carcinoma with NECTIN4 Amplification: 4

Retrospective cohort. N=108. NECTIN4-specific amplifications by FISH assay (NECTIN4/CEN1 ratio) > 2.0. NECTIN4 amplification was associated with enhanced membranous protein expression, as well as objective response to enfortumab vedotin with longer OS and response rate (82% vs 32% non-amplified). References: 38657187

Friday, 26 April 2024 (Version: 20240426AU)

New Tovorafenib in Low-grade gliomas with BRAF V600, V600E, KIAA1549-BRAF fusion,Fusion: 3

Phase 2. FIREFLY-1. PNOC026. n=77. BRAF-altered, relapsed/refractory pediatric low-grade glioma. The primary endpoint was met: ORR was 46/69 (67%) by RANO-HGG criteria. DOR was 16.6 months. References: 37978284

Saturday, 20 April 2024 (Version: 20240420AU)

New EO1001 in Glioblastoma with EGFR Amplification, vIII: 4

Preclinical study. NT113, a pan-ERBB inhibitor with high brain penetrance, showing activity in glioblastoma xenografts model with EGFR amplification and models transfected with vIII. References: 25313012

Sunday, 14 April 2024 (Version: 20240414AU)

New Sunitinib in Breast cancer with FGFR1 Amplification; Oncogenic mutations: R2

NCT02693535. TAPUR. Phase 2. Single agent Sunitinib had ORR of 7% in FGFR1 altered group. DCR was 27% did not meet the prespecified threshold. References: 38354330

New Sunitinib in Breast cancer with FGFR2 Amplification; Oncogenic mutations: R2

NCT02693535. TAPUR. Phase 2. Single agent Sunitinib had DCR of 0% in FGFR2 altered group. References: 38354330

Removed in with alterations : Tier

Saturday, 13 April 2024 (Version: 20240413AU)

New Erdafitinib in Solid tumour with FGFR1 Fusion; FGFR1-TACC1 fusion: 3

Phase 2. NCI-MATCH. EAY131-K2 trial. NCT03198147. N=35. Erdafitinib showed antitumor efficacy in patients with FGFR1-4 mutations or fusions with ORR of 16% (4/25) and Median PFS of 3.6 months. References: 38603650

New Erdafitinib in Solid tumour with FGFR2 S252W; Fusion; FGFR2-ACOT11 fusion; FGFR2-AHCYL1 fusion; FGFR2-FOXP1 fusion; FGFR2-BICC1 fusion;: 3

Phase 2. NCI-MATCH. EAY131-K2 trial. NCT03198147. N=35. Erdafitinib showed antitumor efficacy in patients with FGFR1-4 mutations or fusions with ORR of 16% (4/25) and Median PFS of 3.6 months. References: 38603650

New Erdafitinib in Solid tumour with FGFR3 S249C; Fusion; FGFR3-TACC3 fusion: 3

Phase 2. NCI-MATCH. EAY131-K2 trial. NCT03198147. N=35. Erdafitinib showed antitumor efficacy in patients with FGFR1-4 mutations or fusions with ORR of 16% (4/25) and Median PFS of 3.6 months. References: 38603650

New Erdafitinib in Solid tumour except urothelial carcinoma with FGFR1 Amplification: R2

Phase 2 NCI-MATCH. EAY131-K1 trial. NCT03167159. N=35. Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications. References: 38603651

New Erdafitinib in Solid tumour except urothelial carcinoma with FGFR2 Amplification: R2

Phase 2 NCI-MATCH. EAY131-K1 trial. NCT03167159. N=35. Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications. References: 38603651

New Erdafitinib in Solid tumour except urothelial carcinoma with FGFR3 Amplification: R2

Phase 2 NCI-MATCH. EAY131-K1 trial. NCT03167159. N=35. Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications. References: 38603651

New in with :

References:

Thursday, 4 April 2024 (Version: 20240404AU)

New Talazoparib, Talazoparib + AZD0156 in Pancreatic adenocarcinoma with SF3B1 H662Q, K700E, R625H, R625C, R625L: 4

Preclinical study. Synthetic lethal drug screens revealed that SF3B1 mutant cell lines are selectively sensitive to PARP inhibition in cell line models as well as antitumor effects in in vivo models. References: 37524790

New Regorafenib in Solid tumours with BRAF Oncogenic mutation, Amplification, Fusion, Class I mutation, Class II mutation, Class III mutation, BCAP29-BRAF fusion, SND1-BRAF fusion, D594G, D594N, G466A, G469A, G469R, G469V, G596C, I617V, K601E, N486_P490del, N581I, V487_P492>A, V600E, V600E , V600K: R2

Phase 2. TAPUR. NCT02604757. N=28. Regorafenib did not meet prespecified criteria for activity in patients with solid tumors and BRAF alterations. DCR was 21%. ORR was 7%. References: 10.1200/PO.23.00527

Tuesday, 2 April 2024 (Version: 20240402AU)

Changed Olaparib in Pancreatic adenocarcinoma with ATM Loss-of-function mutations, Truncating mutations, Loss-of-protein expression: R2

Comments changed: Phase 2 single arm study. NCT02677038 and NCT02511223. No responders in 5 patients in the loss-of-protein expression group.Phase 2 single arm study. NCT02677038 and NCT02511223. No objective response in 14 patients in both somatic and germline ATM alteration. No responders in 5 patients in the loss-of-protein expression group..

Monday, 25 March 2024 (Version: 20240325AU)

Changed Pembrolizumab in Head and neck squamous cell carcinoma with CD274 Protein expression

Tier changed: 1B. Comments changed: TGA approved. Not PBS reimbursed. Approved for CPS >= 1; PBS-subsidised if the PD-L1 CPS >= 20 in the tumour sample..

Changed Pembrolizumab + Nab-paclitaxel, Pembrolizumab + Paclitaxel, Pembrolizumab + Carboplatin + Gemcitabine in Triple-negative breast cancer with CD274 Protein expression

Tier changed: 12. Comments changed: TGA approved. KEYNOTE-355: First-line pembrolizumab combination with chemotherapy in TNBC with PD-L1 expression (defined as combined positive score of >= 10%). PFS 9.7 v 5.6mo. Median OS was significantly longer in pembrolizumab plus chemotherapy group (23.0 months) versus chemotherapy alone (16.1 months).Not TGA approved. FDA accelerated approval. KEYNOTE-355: First-line pembrolizumab combination with chemotherapy in TNBC with PD-L1 expression (defined as combined positive score of >= 10%). PFS 9.7 v 5.6mo. Median OS was significantly longer in pembrolizumab plus chemotherapy group (23.0 months) versus chemotherapy alone (16.1 months)..

Changed Pembrolizumab in Cervical cancer with CD274 Protein expression

Tier changed: 1B2. Comments changed: Not TGA approved. KEYNOTE-028: Phase 1b. ORR 17%. KEYNOTE-158: ORR 15%. PD-L1 positivity defined as CPS >= 1% (22C3 pharmDx assay)..

Changed Pembrolizumab + Cisplatin + Fluorouracil in Oesophageal cancer, Oesophageal Adenocarcinoma, Oesophageal squamous cell carcinoma with CD274 Protein expression

Tier changed: 1B2. Comments changed: TGA approved. Phase 3 KEYNOTE-590. FDA approved 2021-03-22. In the first-line setting, adding pembrolizumab to chemotherapy resulted in superior OS in PD-L1 positive subgroups (defined as CPS ≥ 10%, median 13.5 versus 9.4 mo), but also in ESCC and overall populations. Overall ORR in pembrolizumab arm was 45% (vs control 23%)..

Changed Pembrolizumab in Cervical cancer, Endometrial cancer, Neuroendocrine tumour, Salivary gland cancers, Small-cell lung cancer, Thyroid cancer, Vulvar cancer with Tumour Mutational Burden High

Tier changed: 1B2. Comments changed: TGA provisionally approved. KEYNOTE-158. The following cancer types have higher ORR in TMB-H cohort (vs non-TMB-H). TMB cut-off at 10mut/MB.Not TGA approved. KEYNOTE-158. The following cancer types have higher ORR in TMB-H cohort (vs non-TMB-H). TMB cut-off at 10mut/MB..

Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with Tumour Mutational Burden High

Tier changed: 1B2. Comments changed: TGA provisionally approved. Phase 3 CHECKMATE 227. Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort. Median PFS: 7.2 vs 5.5 months. Not correlated with TMB.Not TGA approved. Phase 3 CHECKMATE 227. Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort. Median PFS: 7.2 vs 5.5 months. Not correlated with TMB..

Thursday, 21 March 2024 (Version: 20240321AU)

New Atezolizumab, Pembrolizumab in Solid tumour with CD8 High: 4

To revise. Not for formal curation. References: NCT06003621

Changed Therapy in Solid tumours with CD274 Amplification: 4

Therapy changed: Anti-PD-1 monoclonal antibody, immune checkpoint blockade,PD-L1-targetingAnti-PD-1 monoclonal antibody, immune checkpoint blockade,PD-L1 targeting.

Tuesday, 19 March 2024 (Version: 20240319AU)

New Pembrolizumab + Fluorouracil + Cisplatin, Pembrolizumab + Capecitabine + Oxaliplatin in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2+CD274 CD274:Protein expression and NOT ERBB2:Amplification and NOT ERBB2:Overexpression: 1B

Not PBS listed. TGA approved without biomarker. Phase 3. KEYNOTE-859. NCT03675737. N=1579. Pembrolizumab + chemotherapy significantly improved OS over chemotherapy alone in HER2-negative gastric or gastro-esophageal junction adenocarcinoma. In subgroup analysis, OS (versus placebo) was longer in PD-L1 CPS >= 1 and >= 10 subgroups but not in the <1 subgroup. References: 37875143

Monday, 18 March 2024 (Version: 20240318AU)

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 1B

Comments changed: Not TGA approved. Phase 3. DESTINY-Breast04. NCT03734029. Compared with physician’s choice, T-DXD prolonged both PFS (10.1 v 5.4 months) and OS (23.9 v 17.5 months) in Hormone receptor-positive, HER2-low metastatic breast cancer. Similarly T-DXD also prolonged PFS (9.9 v 5.1 months) and OS (23.4 vs 16.8 months) compared to physician’s choice in the overall population. HER2-Low was defined as IHC a score of 1+ or 2+ with negative results on in situ hybridization. FDA approved 5/8/2022..

Tuesday, 27 February 2024 (Version: 20240227AU)

Monday, 26 February 2024 (Version: 20240226AU)

New Sotorasib, JQD443, RM-018 in Solid tumour with HRAS G12C: 4

Preclinical study. Sotorasib is a potent NRASG12C inhibitor, more potent than KRASG12C (5-fold) in vitro. In addition, sotorasib is also a HRASG12C inhibitor. This was demonstrated by the clinical response of a patient with NRASG12C colorectal cancer treated with sotorasib and panitumumab. References: 38236605

New Sotorasib, JQD443, RM-018 in Solid tumour with NRAS G12C: 4

Preclinical study. Sotorasib is a potent NRASG12C inhibitor, more potent than KRASG12C (5-fold) in vitro. In addition, sotorasib is also a HRASG12C inhibitor. This was demonstrated by the clinical response of a patient with NRASG12C colorectal cancer treated with sotorasib and panitumumab. References: 38236605

New Adagrasib, GDC6036 in Solid tumour with HRAS G12C: R2

Preclinical study. Both adagrasib and GDC6036 are KRAS G12C specific inhibitors. References: 38236605

New Cisplatin + Etoposide, Carboplatin + Etoposide, Olaparib + Temozolomide, Topotecan in Small-cell lung cancer with MYC Amplification: R2

Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients. References: 38386926

New Cisplatin + Etoposide, Carboplatin + Etoposide, Olaparib + Temozolomide, Topotecan in Small-cell lung cancer with MYCL Amplification: R2

Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients. References: 38386926

New Cisplatin + Etoposide, Carboplatin + Etoposide, Olaparib + Temozolomide, Topotecan in Small-cell lung cancer with MYCN Amplification: R2

Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients. References: 38386926

New Adagrasib, GDC6036 in Solid tumour with NRAS G12C: R2

Preclinical study. Both adagrasib and GDC6036 are KRAS G12C specific inhibitors. References: 38236605

Friday, 9 February 2024 (Version: 20240209AU)

Changed Enasidenib in Acute myeloid leukaemia with IDH2 : 1B

Alterations changed: R140Q, R140, R172K, R172SR140Q, R172K, R172S.

Wednesday, 31 January 2024 (Version: 20240131AU)

New PF-07104091 in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Phase 1, NCT04553133. In 16 RECIST evaluable HR+/HER2- metastatic breast cancer, ORR was 19% (n=3). DCR was 62%. References: 10.1200/JCO.2023.41.16_suppl.3010

New PF-07220060 in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Phase 1/2a study. PF-07220060 alone or with endocrine therapy in HR+/HER2- metastatic breast cancer with prior endocrine therapy and CDK4/6 inhibitors exposure. ORR was 29%. Median PFS of 25 weeks. References: 10.1200/JCO.2023.41.16_suppl.3009

Monday, 22 January 2024 (Version: 20240122AU)

New Olaparib, Talazoparib in Acute myeloid leukaemia with IDH1 Oncogenic mutation: 4

In vitro study. Increased DNA damage and sensitization to daunorubicin, ionizing radiation, and PARP inhibitors were observed in IDH1/2MUT AML cells. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells. References: 29339439

New Olaparib, Talazoparib in Acute myeloid leukaemia with IDH2 Oncogenic mutation: 4

In vitro study. Increased DNA damage and sensitization to daunorubicin, ionizing radiation, and PARP inhibitors were observed in IDH1/2MUT AML cells. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells. References: 29339439

Friday, 12 January 2024 (Version: 20240112AU)

Changed Repotrectinib in Non-small cell lung cancer with ROS1 Fusion: 2

References changed: 38197815, 10.1200/JCO.2023.41.16_suppl.9017.

Wednesday, 10 January 2024 (Version: 20240110AU)

New INCB161734 in Solid tumour with KRAS G12D: 4

References: NCT06179160

Sunday, 7 January 2024 (Version: 20240107AU)

New Ripretinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 13 mutation, Exon 11 mutation and Exon 14 mutation: R2

Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. Ripretinib showed significantly inferior PFS to Sunitinib (Median PFS 4.0 v 15.0 months) in patients with KIT exon 13/14 co-mutation. References: 38182785, 10.1200/JCO.2023.41.36_suppl.397784

Changed Sunitinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 13 mutation, Exon 11 mutation and Exon 14 mutation: 3

References changed: 38182785, 10.1200/JCO.2023.41.36_suppl.397784.

Changed Therapy in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation: 3

Therapy changed: RipretinibSunitinib. References changed: 38182785, 10.1200/JCO.2023.41.36_suppl.397784.

Changed Sunitinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation: R2

References changed: 38182785, 10.1200/JCO.2023.41.36_suppl.397784.

Friday, 29 December 2023 (Version: 20231229AU)

New Tamoxifen in Breast cancer with FGFR1 Amplification: R2

Amplification was determined by CISH, if >50% of cells harbored either >5 copies. References: 20179196

Changed Ripretinib in Gastrointestinal stromal tumour with KIT Protein expression; Oncogenic mutations

Tier changed: 1B. Comments changed: TGA approved. PBS Reimbursed for patients with GIST who received prior treatment with 3 or more kinase inhibitors;TGA approved for patients with GIST who received prior treatment with 3 or more kinase inhibitors; Not PBS Reimbursed..

Wednesday, 27 December 2023 (Version: 20231227AU)

New Trastuzumab + Pertuzumab + Paclitaxel in Extramammary Paget’s disease with ERBB2 Overexpression: 4

Case report. Single complete responder to pertuzumab, trastuzumab, and weekly paclitaxel. References: 37595182

New EPI-7386 in Prostate cancer with AR AR-V7: 4

References: 10.1093/annonc/mdz244.065

Tuesday, 26 December 2023 (Version: 20231226AU)

Friday, 22 December 2023 (Version: 20231222AU)

New Vemurafenib in Hairy cell leukaemia, Erdheim-Chester disease with BRAF V600: 3

Phase 2. AcSé vemurafenib basket study. NCT01895643. N=98. Vemurafenib showed clinical activity in BRAF mutated cancers including HCL (ORR 89.7%), ECD (80%), ovarian cancer (50%) and cholangiocarcinoma (18%). Median PFS was 8.8 months. Response were also seen in glioblastoma, ovarian, xanthoastrocytoma, ganglioglioma, sarcoma, GI adenocarcinoma, and prostate cancer. References: 37922690

New Vemurafenib in Solid tumour with BRAF V600: 3

Phase 2. AcSé vemurafenib basket study. NCT01895643. N=98. Vemurafenib showed clinical activity in BRAF mutated cancers including HCL (ORR 89.7%), ECD (80%), ovarian cancer (50%) and cholangiocarcinoma (18%). Median PFS was 8.8 months. Response were also seen in glioblastoma, ovarian, xanthoastrocytoma, ganglioglioma, sarcoma, GI adenocarcinoma, and prostate cancer. References: 37922690

New Dabrafenib + Trametinib in Melanoma with BRAF T599_V600insT: 4

Case series. References: 35319964

New Vemurafenib in Melanoma with BRAF T599_V600insT: 4

Phase 2. AcSé vemurafenib basket study. NCT01895643. One responder seen in melanoma harbouring T599dup. References: 37922690

New Vemurafenib in Melanoma with BRAF T599_V600insT: R2

Case series. No response was seen in two patients with BRAF T599dup. References: 35319964

Wednesday, 20 December 2023 (Version: 20231220AU)

New Atezolizumab + Cobimetinib in Colorectal cancer with KRAS Oncogenic mutations: R2

Phase 3 IMblaze 370 trial. NCT02788279. N=363. Atezolizumab plus cobimetinib did not improve OS compared to regorafenib in patients with MSS colorectal cancer and disease progression on or intolerance to at least two previous chemotherapy regimens. ORR in RAS mutant group was 1/99 (1%). References: 31003911

New Cetuximab, Panitumumab in Colorectal cancer with EGFR G63R, E114K, R165Q, R222C, S492R, P596L, K708R, E709K, G719S, G724S, L858R: 4

Preclinical study. Somatic EGFR mutations in colon cancer were identified by systematic functional screening and demonstrated to be oncogenic, ligand-independent and transform cells in vitro and responsive to cetuximab or panitumumab both in vitro and in vivo. References: 31290142

Sunday, 17 December 2023 (Version: 20231217AU)

New Garsorasib in Colorectal adenocarcinoma with KRAS G12C: 3

Phase I/II (NCT04585035). N=24. D-1553 demonstrated a activity in heavily pretreated CRC with KRAS G12C mutations. Confirmed ORR was 21%. DCR was 96%. References: 10.1200/JCO.2023.41.16_suppl.3563

Saturday, 16 December 2023 (Version: 20231216AU)

New Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 2

Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. OS at 24 months was 83% with dostarlimab and 59% with placebo. References: 36972026

New Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Mismatch repair Deficient: 2

Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. OS at 24 months was 83% with dostarlimab and 59% with placebo. References: 36972026

Changed Enfortumab Vedotin in Urothelial carcinoma with NECTIN4 Protein expression

Tier changed: 12. Comments changed: TGA approved. PBS reimbursed. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells.Not TGA approved. FDA approved. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells..

Thursday, 14 December 2023 (Version: 20231214AU)

New Trametinib in Non-small cell lung cancer with GNAS R201C, R201H: 4

Case report. References: 35946511

New Trametinib in Appendiceal cancer with GNAS R201H: 4

Case report. References: 28868010

New MRTX1719 in Solid tumour, Mesothelioma, Non-small cell lung cancer, Gallbladder cancer, Malignant peripheral nerve sheath tumor with MTAP Deletion: 4

Phase 1 trial and preclinical study. NCT05245500. In vitro cell line models and xenografts studies. MRTX1719 selectively inhibited PRMT5 in MTAP-deleted tumor cells with minimal effects on normal hematopoietic cells. Early clinical activity were observed in patients seleced cancer types. References: 37552839

New Osimertinib in Non-small cell lung cancer with GNAS R201C, R201H: R2

Case report. References: 35946511

Monday, 11 December 2023 (Version: 20231211AU)

Saturday, 9 December 2023 (Version: 20231209AU)

New Mirvetuximab soravtansine in Ovarian cancer with FOLR1 Protein expression: 2

Phase 3 trial. MIRASOL. NCT04209855. N=453. In platinum-resistant ovarian cancer, Mirvetuximab soravtansine showed significant improvement in PFS (median, 5.6 months v chemotherapy, 3.9 months), ORR (42% vs 16%) and OS (16.5 vs 12.8 months) over chemotherapy. References: 38055253

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with ALK EML4-ALK fusion: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with BRAF Amplification, V600E: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with EGFR Amplification: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with ERBB2 Amplification: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with HRAS G13V: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with KRAS Amplification, A11_G12delinsGD, G12R, G12S, G13D, H95N, Q61H, Q61L, R68S, Y96D: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with MAP2K1 E203K, K57N, Q56P: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with MET Amplification: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with MYC Amplification: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with NF1 Deletion: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with NRAS Amplification, G13R, Q61R: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with PIK3CA E545K: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with PIK3R2 G373R: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with PTEN Oncogenic mutation, Deletion: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with RET CCDC6-RET fusion: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with ROS1 GOPC-ROS1 fusion: R2

Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910

Changed Divarasib + Cetuximab in Colorectal cancer with KRAS G12C: 2

Comments changed: Phase 1b trial. NCT04449874. GO42144. N=29. Divarasib plus cetuximab had a manageable safety profile and encouraging antitumor activity in KRAS G12C-positive CRC. The confirmed ORR was 63% (18/29, KRAS G12C inhibitor-naive patients). The median duration of response was 6.9 months, and the median PFS was 8.1 months.Phase 1b. NCT04449874. Confirmed ORR of 62% (18/29). Ongoing study.. References changed: 3805291010.1158/1538-7445.AM2023-CT029.

Changed Buparlisib in Urothelial carcinoma with TSC1 Oncogenic mutations: R2

Comments changed: Phase 2. N=19. Buparlisib had modest activity in patients with metastatic UC whose tumors harbored TSC1 loss of function alterations (6 SD and one PR at 8 weeks on therapy)..

Friday, 8 December 2023 (Version: 20231208AU)

New MTYX-5000 in Solid tumour, Non-small cell lung cancer with MET Overexpression: 4

Preclinical study. MYTX-011 showed activities in higher internalization in cMet+ tumor cells, cytotoxicity across a cMet+ cancer cell lines in vitro, and in NSCLC xenograft models. References: 10.1158/1538-7445.AM2023-5000

Wednesday, 6 December 2023 (Version: 20231206AU)

New GQ1001 in Solid tumour with ERBB2 Overexpression, amplification: 4

References: 10.1158/1538-7445.AM2023-2702

New INX-315 in Breast cancer with ESR1 Protein expression: 4

Preclinical study. INX-315 induces senescence in CCNE1-amplified luminal breast cancer cell lines, leading to growth control and overcoming and delaying breast cancer resistance to CDK4/6i. References: 38047585

New INX-315 in Breast cancer with ESR1+CCNE1 ESR1:Protein expression and CCNE1:Amplification: 4

Preclinical study. INX-315 induces senescence in CCNE1-amplified luminal breast cancer cell lines, leading to growth control and overcoming and delaying breast cancer resistance to CDK4/6i. References: 38047585

Changed BI-1810631 in Solid tumours with ERBB2 : 4

Alterations changed: Oncogenic mutations, Amplification.

Changed Divarasib + Cetuximab in Colorectal cancer with KRAS G12C

Tier changed: 24.

Changed Therapy in Prostate cancer with AR AR-V7: R2

Therapy changed: Abiraterone acetate, Enzalutamide, Androgen receptor antagonist, CYP17A1 inhibitor. Comments changed: Phase 2. Detection of AR-V7 circulating tumour cells in metastatic castration resistant prostate cancer patients treated with enzalutamide or abiraterone showed a significant lower PFS, OS, and response rate compared to those without AR-V7..

Tuesday, 5 December 2023 (Version: 20231205AU)

New Garsorasib in Non-small cell lung cancer with KRAS G12C: 3

Phase 1. NCT04879671. N=79 (combined dose escalation and expansion). In patients with KRAS G12C mutated NSCLC, Treatment with D-1553 (Garsorasib) resulted in ORR of 40% and DCR of 92%. Median PFS was 8 months. References: 36948246

New Ipilimumab + Nivolumab in Solid tumour with ATM Oncogenic mutation: R2

Phase 2. TAPUR study. NCT02693560. N=29. ORR and PFS for nivolumab + ipilimumab in patients with ATM mutation (ORR 14%, DC rate 24%) did not meet the prespecified endpoints. References: 38039429

Wednesday, 29 November 2023 (Version: 20231129AU)

New Capivasertib + Fulvestrant in Breast cancer with AKT1 Oncogenic mutation: 2

Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy. References: 37256976

New Capivasertib + Fulvestrant in Breast cancer with PIK3CA Oncogenic mutation: 2

Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy. References: 37256976

New Capivasertib + Fulvestrant in Breast cancer with PTEN Loss-of-function mutations, deletion: 2

Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy. References: 37256976

Changed Olaparib in Prostate cancer with BRCA1 Oncogenic mutations: 1

Comments changed: TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). Olaparib was associated with longer rPFS over control (HR, 0.22) and OS (HR, 0.63). rPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16).TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control).

Changed Olaparib in Prostate cancer with BRCA2 Oncogenic mutations: 1

Comments changed: TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). Olaparib was associated with longer rPFS over control (HR, 0.22) and OS (HR, 0.63). rPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16).TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control)..

Changed Nirogacestat in Aggressive fibromatosis with APC Oncogenic mutations: 2

Comments changed: Not TGA approved. FDA approved 27/11/2023. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.Not TGA approved. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria..

Changed Nirogacestat in Aggressive fibromatosis with CTNNB1 Oncogenic mutations: 2

Comments changed: Not TGA approved. FDA approved 27/11/2023. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.Not TGA approved. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria..

Changed Talazoparib in Solid tumour except Breast cancer with ATM Oncogenic mutations (germline), Oncogenic mutations: R2

Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene..

Changed Talazoparib in Solid tumour except Breast cancer with ATR Oncogenic mutation: R2

Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene..

Changed Talazoparib in Solid tumour except Breast cancer with BRIP1 Oncogenic mutation: R2

Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene..

Changed Talazoparib in Solid tumour except Breast cancer with CHEK2 Oncogenic mutation: R2

Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene..

Changed Talazoparib in Solid tumour with PTEN Loss-of-function mutations, deletion: R2

Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene..

Changed Talazoparib in Solid tumour except Breast cancer with RAD50 Oncogenic mutation: R2

Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene..

Tuesday, 28 November 2023 (Version: 20231128AU)

New Talazoparib in Solid tumour except Breast cancer with ATM Oncogenic mutations (germline), Oncogenic mutations: R2

References: 36253484

New Talazoparib in Solid tumour with PTEN Loss-of-function mutations, deletion: R2

References: 36253484

New Talazoparib in Solid tumour except Breast cancer with RAD50 Oncogenic mutation: R2

References: 36253484

New Talazoparib in Solid tumour except Breast cancer with BRIP1 Oncogenic mutation: R2

References: 36253484

New Talazoparib in Solid tumour except Breast cancer with CHEK2 Oncogenic mutation: R2

References: 36253484

New Talazoparib in Solid tumour except Breast cancer with ATR Oncogenic mutation: R2

References: 36253484

New Talazoparib in Breast cancer with PALB2 Oncogenic mutations (germline): 3

Phase 2. NCT02401347. PFS was 6.5 months (95% CI, 2.8-10.2) in patients with pretreated advanced HER2-negative breast cancer and other solid tumors with mutations in homologous recombination pathway genes other than BRCA1/2. In patients with breast cancer, overall response rate was 31% (4 partial responses), and clinical benefit rate was 54%. All patients with germline mutations in PALB2 had treatment-associated tumor regression. References: 36253484

New Apalutamide + Goserelin in Salivary gland cancers with AR Protein expression: 3

Phase 2. NCT04325828. AR-expressing SGC, pts treated with APA and GOS. ORR (6/24) was 25%. Clinical benefit rate and DCR were 50% and 70.8%, respectively. PFS and OS in the treated pts were 7.4 months and not reached, respectively. References: 10.1200/JCO.2022.40.16_suppl.6079

Monday, 27 November 2023 (Version: 20231127AU)

New Trastuzumab in Breast cancer with PTEN Loss-of-function mutations, deletion: R2

Preclinical study. Trastuzumab treatment increased the phosphatase activity of PTEN via Src inhibition. Patients with PTEN deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal PTEN. References: 15324695

Saturday, 25 November 2023 (Version: 20231125AU)

Changed Talazoparib in Acute myeloid leukaemia with PTEN : 4

Alterations changed: Loss-of-function mutations, deletion.

Wednesday, 22 November 2023 (Version: 20231122AU)

New ELVN-002 in Solid tumour with ERBB2 Exon 20 insertion, A775_G776insYVMA, G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVCS310Y, R678Q, L755S, L755P, D769N, V773M, V777L, L869R, L869R and T798I, V842I: 4

Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019

New Tucatinib in Solid tumour with ERBB2 S310F, S310Y, R678Q, D769N, V773M, V777L, V842I, P780_Y781insGSP, V777_G778insGC: 4

Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019

New Tucatinib in Solid tumour with ERBB2 Exon 20 insertion, T798M, A775_G776insYVMA, G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVC: R2

Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019

New ELVN-002 in Solid tumour with ERBB2 T798M: R2

Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019

New Talazoparib in Acute myeloid leukaemia with PTEN Loss-of-function mutations: 4

References: 10.1182/blood-2021-146694

Tuesday, 21 November 2023 (Version: 20231121AU)

New Buparlisib in Glioblastoma with PIK3CA Oncogenic mutation: R2

Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months. References: 30715997

New Buparlisib in Glioblastoma with PIK3R1 Oncogenic mutation: R2

Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months. References: 30715997

New Buparlisib in Glioblastoma with PTEN Oncogenic mutations; Deletions; Loss of protein expression: R2

Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months. References: 30715997

Monday, 20 November 2023 (Version: 20231120AU)

New FORE8394 in Solid tumour with BRAF V600, fusions: 3

Phase 1/2a FORE8394-201 study. NCT02428712. N=110. ORR in the treatment naive cohort was 39% (9/23); 18% (3/17) in previously treated with MAPKi. References: 10.1200/JCO.2023.41.16_suppl.3006

New KL590586 in Solid tumour with RET Fusions, Oncogenic mutations: 3

Phase I KL400-I/II-01 trial. NCT05265091. In the dose expansion part (n=69), ORR was 64% in RET altered tumors including NSCLC, MTC, pancreatic cancer and ovarian cancer. ORR in systemic pretreated NSCLC was 63%, DCR 91%. ORR in treatment nave NSCLC was 76% with DCR of 92%. CNS DCR was 100%. References: 10.1200/JCO.2023.41.16_suppl.3007

New PRT811 in High-grade gliomas with IDH1 R132: 4

Phase 1 dose-expansion trial. NCT04089449. In IDH1/2-mutated glioma (n=16), PRT811 treatment was associated with 2 CR (1 durable) and 1 unconfirmed PR. References: 10.1200/JCO.2023.41.16_suppl.3008

Friday, 17 November 2023 (Version: 20231117AU)

New Repotrectinib in Non-small cell lung cancer with ROS1 Fusion: 2

Phase 2 NCT03093116. TRIDENT-1 trial. N=296. Repotrectinib showed durable clinical activity in ROS1 TKI-naïve (ORR=88%) and -pretreated pts with or without BL CNS mets, including intracranial responses. References: 10.1200/JCO.2023.41.16_suppl.9017

Changed Vemurafenib in Erdheim-Chester disease, Langerhans Cell Histiocytosis with BRAF V600E: 2

Comments changed: Not TGA approved. Not PBS reimbursed. FDA approved. Secondary analysis of VE-BASKET study showed 62% confirmed ORR by RECIST and 100% PET response arte. PFS rate at 2 year was 86%.Not TGA approved. Not PBS reimbursed. Secondary analysis of VE-BASKET study showed 62% confirmed ORR by RECIST and 100% PET response arte. PFS rate at 2 year was 86%..

Changed Cobimetinib in Histiocytosis with BRAF V600E, N486_T491del

Tier changed: 23. Comments changed: Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations.Signal of activity in phase 2 trial.

Changed Cobimetinib in Histiocytosis with KRAS G12R, G13C, R149C

Tier changed: 23. Comments changed: Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutationsPhase II Umbrella study.

Changed Cobimetinib, Trametinib in Histiocytosis with MAP2K1 P142L, P124Q, Q56P, P105_107del

Tier changed: 23.

Changed Cobimetinib in Histiocytosis with MAP2K2 Oncogenic mutations, Y134H

Tier changed: 23.

Changed Cobimetinib in Histiocytosis with ARAF Oncogenic mutations, P216A: 4

Comments changed: Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations. No cases with isolated ARAF responded to cobimetinibOncoKB LOE 3; No cases with isolated ARAF responded to cobimetinib.

Tuesday, 14 November 2023 (Version: 20231114AU)

New Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 1B

Phase 3 FLAURA2 trial. NCT04035486. N=557. Combination of osimertinib with pemetrexed and a platinum agent led to significantly longer PFS over osimertinib monotherapy (19.3 v 11.2 months). ORR was similar between arms at 80% (osimertinib) and 84% (combination). References: 37937763

New Trastuzumab deruxtecan in Non-small cell lung cancer with ERBB2 Oncogenic mutation: 2

Phase 2 trial. DESTINY-Lung02. NCT04961073. N=152. Dose optimization study. Confirmed ORR was 49% (Median DOR 16.8 months) and 56% (NE) in T-DXd 5.4mg/kg and 6.4 mg/kg respectively. Grade ≥3 treatment related adverse events occurred in 38.6% and 58% of patients receiving 5.4 and 6.4 mg/kg, respectively. References: 37694347

New Tipifarnib in Head and neck squamous cell carcinoma with HRAS Oncogenic mutations, G12C, G12D, G12S, G13R, G13V: 3

Kura data set (NCT02383927) showed median DFS of 4.0 months (range 1-63 months, n=27), and OS of 25.5 months (range 4-94 month, n=27). Median OSmet was 15.0 months (range 1-47 months, n=27). MDACC data set showed median DFS of 4.0 months (n=12), and OS of 15 months (n=12). Median OSmet was 12 months (n=12). References: 36603172

New Ipatasertib in Solid tumour with AKT1 LAMTOR1-AKT1 fusion: 4

Case report. A paediatric patient with histopathologically indeterminate epithelioid neoplasm harbouring a novel fusion LAMTOR1-AKT1 treated with ipatasertib resulted in dramatic tumour regression. Confirmation in the in vitro models confirmed the fusion led to activation of AKT1. References: 30877085

New RMC-6236 in Pancreatic adenocarcinoma, Non-small cell lung cancer with KRAS G12, G12D, G12V, G12R, G12D, G12V, G12A: 4

Phase 1 trial. NCT04896732. N=33. in patients with KRASG12X, preliminary anti-tumor activity was seen with RMC-6236 pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). Objective response rate was 36% (2 / 10 confirmed, 3 / 4 unconfirmed), median time to onset of initial response was 6 weeks, disease control rate was 86. References: 10.1016/j.annonc.2023.09.1838

New HRS-4642 in Solid tumour with KRAS G12D: 4

Phase 1 trial. NCT05597436. N=18. One NSCLC patient at 200 mg had PR, and 11/18 pts (61.1%) had SD with 33.3% experienced target lesion shrinkage. References: 10.1016/j.annonc.2023.10.025

New Palbociclib, Ribociclib in Solid tumour with CDK4 Amplification: R2

Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations. References: 37424386

New Palbociclib, Ribociclib in Solid tumour with CDK6 Amplification: R2

Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations. References: 37424386

New Palbociclib, Ribociclib in Solid tumour with CDKN2A Oncogenic mutations, deletions, Truncating mutations, Loss-of-function mutations: R2

Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations. References: 37424386

New Tipifarnib in Salivary gland cancers, Salivary duct carcinoma, Epithelial-myoepithelial carcinoma with HRAS Oncogenic mutation; Q61R: R2

Phase 2. NCT02459813. N=13. Tipifarnib demonstrated a modest clinical activity in HRAS-mutant, R/M SGC with a DCR of 58%. One objective response was observed. 7 patients had SD as their best response. The median PFSwas 7 months. the median OS was 18 months. References: 32557577

Sunday, 29 October 2023 (Version: 20231029AU)

New Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 1B

TGA approved. Not PBS reimbursed. Phase 3 trial. IMCgp100-202. NCT03070392. HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Median OS was significantly longer in tebentafusp group compared to control (21.6 versus 16.9 months). ORR was 14% (Control 5%). References: 37870955

New Selpercatinib in Non-small cell lung cancer with RET Fusion, KIF5B-RET fusion, CCDC6-RET fusion, NCOA4-RET fusion, KIF13A-RET fusion, KIAA1549L-RET fusion, KIAA1468-RET fusion, PRKAR1A-RET fusion: 1B

TGA approved. Not PBS reimbursed. Phase 3 trial. LIBRETTO-431. NCT04194944. N=261. Selpercatinib (1st line) improved PFS over chemoimmunotherapy (24.8 vs 11.2 months). ORR was similar between the two arms at 84% and 65%. The cause-specific hazard ratio for the time to CNS progression was 0.28. References: 37870973

New Amivantamab + Carboplatin + Pemetrexed in Non-small cell lung cancer with EGFR Exon 20 insertion: 2

Not TGA approved. Not FDA approved. Phase 3 trial. PAPILLON. NCT04538664. N=308. Amivantamab-chemotherapy (carboplatin-pemetrexed) was associated with superior progression-free survival (11.4 months versus 6.7 months) and a higher overall response rate (73% vs 47%) compared to chemotherapy alone in patients with advanced NSCLC with EGFR exon 20 insertions as first line treatment. References: 37870976

New Erdafitinib in Urothelial carcinoma with FGFR3 S249C, Y373C, R248C, G370C, Fusion, FGFR1-TACC3:fusion, FGFR1-TACC3:fusion_V1, FGFR1-TACC3:fusion_V3, FGFR3-BAIAP2L1 fusion: 2

Not TGA approved. FDA approved. Phase 3 trial. THOR. NCT03390504. In the subsequent line setting, Erdafitinib resulted in significantly longer overall survival than chemotherapy (12.1 months vs 7.8 months) among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti-PD-1 or anti-PD-L1 treatment. ORR were 39% (Erdafitinib), versus 10% (Chemotherapy). References: 37870920

New Selpercatinib in Medullary thyroid cancer with RET Oncogenic mutation, M918T: 2

Not TGA approved. FDA approved. Phase 3 trial. LIBRETTO-531. NCT04211337. N=291. Selpercatinib had significantly longer PFS (HR, 0.28) and Treatment failure-free survival (HR, 0.25) compared to control group (cabozantinib or vandetanib) as first-line therapy in RET-mutant medullary thyroid cancer. ORR was 70% (cabozantinib/vandetanib: 39%). Adverse events led to dose reduction in 38.9% of the patients in selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively. References: 37870969

New Tarlatamab in Small-cell lung cancer with DLL3 Protein expression: 3

Phase 2. DeLLphi-301. NCT05060016. N=220. In patients with previously treated extensive stage SCLC. Tarlatamab showed antitumor activity, with ORR of 32-40% across seen in different dose groups and durable objective responses (>6 months) in 40 of 68 (59%) patients. Note DLL3 expression was not required as per trial eligibility but ubiquitously expressed in SCLC. Objective responses were seen in patients with both positive, negative DLL3 expression. References: 37861218

Removed Palbociclib + Avelumab in Solid tumours with CCND1 alterations Amplification: Tier 4

Removed Palbociclib + Avelumab in Solid tumours with CCND2 alterations Amplification: Tier 4

Removed Palbociclib + Avelumab in Solid tumours with CCND3 alterations Amplification: Tier 4

Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01

Tier changed: 1B2. Comments changed: TGA approved. Not PBS reimbursed. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%.Not TGA approved. FDA approved. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%..

Changed Selpercatinib in Non-small cell lung cancer with RET Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion

Tier changed: 1B2. Comments changed: TGA approved. Not PBS reimbursed. FDA Approved 21/09/2022. LIBRETTO-001: First-line treatment. ORR 85%.Not TGA approved. FDA Approved 21/09/2022. LIBRETTO-001: First-line treatment. ORR 85%..

Wednesday, 25 October 2023 (Version: 20231025AU)

New Sotorasib + Panitumumab in Colorectal cancer with KRAS G12C: 2

Phase 3 trial. CodeBreaK 300. NCT05198934. N=160. Sotorasib + panitumumab showed longer progression-free survival (PFS) than standard treatment in chemorefractory metastatic colorectal cancer with mutated KRAS G12C. Median PFS: 5.6 months and 3.9 months for sotorasib at doses of 960 mg and 240 mg, respectively; 2.2 months for standard treatment (HR, 0.49 and 0.58, respectively). Overall survival data are maturing. Objective response rate: 26.4%, 5.7%, and 0% in the sotorasib-panitumumab groups and standard-care group, respectively. Treatment-related adverse events of grade 3 or higher occurred in 35.8%, 30.2%, and 43.1% of patients, respectively. References: 37870968

New AZD9574 in Solid tumour with BRCA1 Oncogenic mutations: 4

Preclinical study. PARP inhibitor (AZD9574) demonstrated potent anti-tumor activity and selectivity towards HRD+ models, showing dose-dependent efficacy in a BRCA1/2 mutant cell line, subcutaneous xenograft, and intracranial breast cancer brain metastases models. References: 10.1158/1538-7445.AM2022-2609

New AZD9574 in Solid tumour with BRCA2 Oncogenic mutations: 4

Preclinical study. PARP inhibitor (AZD9574) demonstrated potent anti-tumor activity and selectivity towards HRD+ models, showing dose-dependent efficacy in a BRCA1/2 mutant cell line, subcutaneous xenograft, and intracranial breast cancer brain metastases models. References: 10.1158/1538-7445.AM2022-2609

New Imatinib in Melanoma with CTNNB1+KIT CTNNB1:S33C and KIT:L576P: R2

Preclinical study. In a single patient case report, CTNNB1 mutation was identified in paired biopsy samples from a patient who had an initial response and later developed resistance to imatinib. Ba/F3 cell line model showed that the combination of KIT L576P mutation with CTNNB1 S33C mutation conferred acquired resistance to imatinib. References: 28421416

Monday, 23 October 2023 (Version: 20231023AU)

New Enzalutamide + Talazoparib in Prostate cancer with BRCA1 Oncogenic mutation: 2

NOT TGA approved. Phase 3 TALAPRO-2 trial. NCT03395197. N=805. Talazoparib plus enzalutamide significantly improved rPFS over placebo (not reached versus 21.9 months) in the first-line castrate-resistant setting. The benefit was observed in both HRR deficient and non-deficent groups, although significant higher HR reduction was seen in the BRCA1/2 deficient subgroup treated with Enzalutamide + Talazoparib. References: 37285865

New Enzalutamide + Talazoparib in Prostate cancer with BRCA2 Oncogenic mutation: 2

NOT TGA approved. Phase 3 TALAPRO-2 trial. NCT03395197. N=805. Talazoparib plus enzalutamide significantly improved rPFS over placebo (not reached versus 21.9 months) in the first-line castrate-resistant setting. The benefit was observed in both HRR deficient and non-deficent groups, although significant higher HR reduction was seen in the BRCA1/2 deficient subgroup treated with Enzalutamide + Talazoparib. References: 37285865

Tuesday, 17 October 2023 (Version: 20231017AU)

New Encorafenib + Binimetinib in Non-small cell lung cancer with BRAF V600E: 2

Not TGA approved. FDA approved. Phase 2, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer. NCT03148795. PHAROS. N=98. ORR was 75% (treatment naive) and 46% (previously treated). DCR after 24 weeks was 64% in treatment-naïve and 41% in previously treated patients. Median PFS was NE in treatment-naïve and 9.3 months in previously treated patients. References: 37270692

New PLX2853, PLX2853 + carboplatin in Ovarian Cancer with ARID1A Oncogenic mutation: R2

Phase Ib/IIa trial. NCT02794586. N=37. PLX2853 monotherapy and combination therapy with carboplatin demonstrated a best ORR of 1 PR (7%). The trial did not meet the prespecified response criteria. References: 37797273

Wednesday, 11 October 2023 (Version: 20231011AU)

New Rucaparib in Mesothelioma with BAP1 Loss of protein expression: 3

Phase 2 MiST. NCT03654833. Ten and 23 of 26 patients were BRCA1 and BAP1 protein expression negative, respectively. DCR at 12 week was 58%, and 23% at 24 weeks, meeting prespecified criteria. References: 33515503

New Vemurafenib + Obinutuzumab in Hairy cell leukaemia with BRAF V600E: 3

Phase 2. NCT03410875. N=30. Vemurafenib plus obinutuzumab achieved CR in more than 90% of patients with previously untreated HCL. Acquired vemurafenib resistance or dose-limiting toxicity was not observed in this small study. References: 10.1056/EVIDoa2300074

New Rucaparib in Mesothelioma with BRCA1 Loss of protein expression: 3

Phase 2 MiST. NCT03654833. 10 and 23 of 26 patients were BRCA1 and BAP1 protein expression negative, respectively. DCR at 12 week was 58%, and 23% at 24 weeks, meeting prespecified criteria. References: 33515503

New ARV-471 in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Phase 1/2 study (VERITAC). NCT04072952. In ARV-471 monotherapy for ER+/HER2- metastatic breast cancer, CBR was 40% at 24 weeks and independent of ESR1 mutation (including 3 PR). All patients received prior CDK4/6 inhibitors, and majority received prior fulvestrant and prior chemotherapy. References: 10.1158/1538-7445.SABCS22-GS3-03

New HMBD-001 in Solid tumour with ERBB3 Extracellular domain mutations: 4

References: NCT05919537

Monday, 2 October 2023 (Version: 20231002AU)

New Olaparib + Durvalumab in Solid tumours with ATM Oncogenic mutation: 3

Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 38% and ORR was 3 /32 (9%) non-BRCA-mutated groups. Only responders were seen in patients with ATM mutations. References: 37365284

New Olaparib + Durvalumab in Solid tumours with BRCA2 Oncogenic mutation: 3

Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 35% and ORR was 3 /16 (19%) BRCA-mutated groups. All responders harboured BRCA2 mutations. References: 37365284

New Olaparib + Durvalumab in Solid tumours with BRCA1 Oncogenic mutation: 4

Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 35% and ORR was 3 /16 (19%) BRCA-mutated groups, although no responders were seen in 4 patients with BRCA1 mutations. References: 37365284

Wednesday, 27 September 2023 (Version: 20230927AU)

New Oxaliplatin, Cisplatin in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 4

References: 35135099

New Oxaliplatin, Cisplatin in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 4

References: 35135099

Changed Dabrafenib + Trametinib in High-grade gliomas with BRAF V600

Tier changed: 23. References changed: 37643378, 10.1200/JCO.2022.40.16_suppl.2009.

Changed Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600

Tier changed: 23. References changed: 10.1056/NEJMoa2303815, 10.1200/JCO.2022.40.17_suppl.LBA2002.

Friday, 15 September 2023 (Version: 20230915AU)

New Talazoparib + VX-970 in Prostate cancer with TP53+RB1 TP53:Oncogenic mutations AND RB1:Oncogenic mutations, TP53:Oncogenic mutations AND RB1:Deletion: 4

Cell line study. Prostate cancers with TP53 and RB1 loss may be associated with poor outcomes, stem-like properties, and may exhibit loss of AR activity. TP53/RB1 mutants are sensitive to PARP and ATR inhibition in cell-line models. References: 32460015

Changed Nimotuzumab + Gemcitabine in Pancreatic adenocarcinoma with KRAS NOT oncogenic mutations: 2

References changed: 37647576; 10.1200/JCO.2022.40.17_suppl.LBA4011.

Changed ABBV-400 with MET Overexpression: 4

Cancer type(s) changed: Non-small cell lung cancer, Gastroesophageal junction adenocarcinoma, Gastric Cancer, Endometrial carcinoma, Acral melanomaNon-small cell lung cancer, Gastroesophageal junction adenocarcinoma, Gastric Cancer, Endometrial carcinoma, Arcal melanoma

Wednesday, 13 September 2023 (Version: 20230913AU)

New Lenvatinib + Pembrolizumab in Endometrial cancer with Mismatch repair Deficient: 1

PBS reimbursed. TGA approved. FDA Approved. In KEYNOTE-775, median PFS was 10.7 v 3.7 months and OS was not reached vs 8.6 months for dMMR population. Note Benefits were seen in both pMMR and dMMR populations, and the TGA approval was irrespective of MMR status. References: 30922731, 32167863

New Pemigatinib in Glioblastoma, Cervical cancer with FGFR3 Fusion: 3

Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016

New ABBV-400 in Non-small cell lung cancer, Gastroesophageal junction adenocarcinoma, Gastric Cancer, Endometrial carcinoma, Arcal melanoma with MET Overexpression: 4

Phase 2. NCT05029882. Clinical activity was observed with ABBV-400 with an ORR of 24% (11/45). All responses were confirmed partial responses. DCR was 81%. Overexpression was determined IHC. References: 10.1200/JCO.2023.41.16_suppl.3015

New Larotrectinib in Low-grade spindle cell neoplasm, Solid tumour with BRAF BRAF-CREB3L2 rearrangement, amplification: R2

Case report. References: 37666486

New Palbociclib in Solid tumour except Breast cancer with CCND1 Amplification: R2

Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months. References: 36853016

New Palbociclib in Solid tumour except Breast cancer with CCND2 Amplification: R2

Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months. References: 36853016

New Palbociclib in Solid tumour except Breast cancer with CCND3 Amplification: R2

Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months. References: 36853016

New Larotrectinib in Low-grade glioma, Low-grade spindle cell neoplasm, Solid tumour with CDKN2A Deletion: R2

Case reports. References: 37666486

New Larotrectinib in Low-grade glioma with EGFR Amplification: R2

Case report. References: 37666486

Changed Lenvatinib + Pembrolizumab in Endometrial cancer with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient

Tier changed: 1B. Comments changed: PBS reimbursed. TGA approved. FDA Approved. In KEYNOTE-146: ORR was 38% (out of 94 patients) including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS). In the confirmatory trial (KEYNOTE-775), primary point was met in non-MSI-H/dMMR patients who have progressed through one previous line of platinum-based chemotherapy: median PFS was 6.6 (pembrolizumab + lenvatinib) vs 3.8 months (investigator choice of chemotherapy) and median OS: 17.4 vs 12 months (chemotherapy). ORR: 30% vs 15%. Note Benefits were seen in both pMMR and dMMR populations, and the TGA approval was irrespective of MMR status.TGA provisional approval. FDA Approved. In KEYNOTE-146: ORR was 38% (out of 94 patients) including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS). In the confirmatory trial (KEYNOTE-775), primary point was met in non-MSI-H/dMMR patients who have progressed through one previous line of platinum-based chemotherapy: median PFS was 6.6 (pembrolizumab + lenvatinib) vs 3.8 months (investigator choice of chemotherapy) and median OS: 17.4 vs 12 months (chemotherapy). ORR: 30% vs 15%..

Changed Pemigatinib: 3

Cancer type(s) changed: Glioblastoma, Diffuse astrocytoma, Cervical cancer Biomarker changed: FGFR1FGFR3. Alterations changed: Fusion; K656E.

Friday, 8 September 2023 (Version: 20230908AU)

New Savolitinib in Gastroesophageal junction adenocarcinoma, Gastric Cancer with MET Amplification: 2

Not TGA approved. Not FDA approved. Phase 2. NCT04923932. Savolitinib monotherapy showed ORR of 45% in MET-amplified gastric cancer or gastro-oesophageal junction adenocarcinoma especially in those with high MET gene copy number. DOR rate at 4-month was 86%. References: 10.1158/1538-7445.AM2023-CT152

New Volasertib, AZD7762 in Triple-negative breast cancer with RB1 Oncogenic mutations: 4

References: 29386107

Changed ONC201 in Diffuse Midline Glioma with TP53 : R2

Alterations changed: Oncogenic mutations.

Tuesday, 5 September 2023 (Version: 20230905AU)

New Afatinib, Poziotinib, Poziotinib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia with ERBB2 R188C, P489L, L1157R: 4

References: 32366937

New Gefitinib, Erloginib, Lapatinib, Canertinib, Pelitinib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia with ERBB2 R188C, P489L, L1157R: 4

References: 32366937

Monday, 4 September 2023 (Version: 20230904AU)

New SN-38 + VE-822 in Colorectal adenocarcinoma with ATR Oncogenic mutation: 4

Cell line study. Heterozygous mutation in ATR renders the cells more susceptible to SN-38 and ATR inhibition, resulting in resulting in DNA damage, depletion of RPA. Consequently, leading to replication catastrophe. References: 35361811

New Patritumab deruxtecan in Breast cancer with ERBB3 V104M, A232V, P262H, G284R, Q809R, S846I, E928G: 4

Cell line study. Patritumab deruxtecan demonstrated in vitro activity against breast cancer cell line transduced to expressmutated HER3. References: 35503762

New ONC201 + Paxalisib in Diffuse Midline Glioma with H3F3A K27M, K28M: 4

Case reports. ONC201 + Paxalisib in two DIPG patients with H3.1K27M and H3.3K27M altered midline glioma.]. References: 37145169

New ONC201 in Diffuse Midline Glioma with TP53 Oncogenic mutation: R2

Drug screening. Reduced sensitivity to ONC201 was found in DIPG cell lines harbouring TP53 mutantion. References: 37145169

Changed Rucaparib in Ovarian cancer with BRCA2 Oncogenic mutations: 2

References changed: 3565848710.1200/JCO.22.01003.

Changed Rucaparib in Ovarian cancer with Homologous Recombination Deficiency Score High: 2

References changed: 3565848710.1200/JCO.22.01003.

Changed Lapatinib in Glioblastoma with PTEN Loss of protein expression: R2

Comments changed: Phase 1/2 trial. Lapatinib. Recurrent GBM. ORR 0%..

Changed Berzosertib + Irinotecan in Gastric cancer, Gastroesophageal junction adenocarcinoma with TP53 : R2

Alterations changed: Oncogenic mutations.

Thursday, 24 August 2023 (Version: 20230824AU)

New Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with KRAS G12C: 3

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. N=137 (NSCLC=60, Colorectal cancer =55, other solid tumors=22). ORR in NSCLC was 53% with PFS: 13.1 months. ORR in CRC was 29% with PFS of 5.6 months. Responses also seen in other solid tumors. References: 37611121

New LY3410738 in Cholangiocarcinoma with IDH1 R132C+D279N: 4

Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib related to the treatment-emergent D279N mutation showed sensitivity to LY3410738. References: 36056177

New Divarasib in Colorectal adenocarcinoma with ALK EML4-ALK fusion: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Divarasib in Colorectal adenocarcinoma, Solid tumours with BRAF G469A, L597Q, L597R, V600E, K601E: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Divarasib in Colorectal adenocarcinoma with ERBB2 Amplification: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Ivosidenib in Cholangiocarcinoma with IDH1 D279N: R2

Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib is related to the treatment-emergent D279N mutation, where the double mutant showed impaired binding to ivosidenib despite reduced efficiency in producing 2HG. References: 36056177

New Ivosidenib in Cholangiocarcinoma with IDH2 R172K: R2

Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib is related to the treatment-emergent IDH2 R172 mutation. References: 36056177

New Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with KRAS Amplification, G12A, G12D, G12R, G12V, G13D, R68S, H95R, Y96D, Y96H, Y96N, Q99L, A146T, Oncogenic mutation AND NOT G12C: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with MAP2K1 Q56P, K57N, E203K: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Divarasib in Colorectal adenocarcinoma with NRAS G13R: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Divarasib in Colorectal adenocarcinoma with PIK3CA E545K: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Divarasib in Solid tumours with PTEN Deletion: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

New Divarasib in Solid tumours with RB1 Deletion: R2

Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121

Changed Niraparib + Abiraterone Acetate in Prostate cancer with BRCA1 Oncogenic mutations: 2

References changed: 3695263436952642.

Changed Niraparib + Abiraterone Acetate in Prostate cancer with BRCA2 Oncogenic mutations: 2

References changed: 3695263436952642.

Changed Therapy in Colorectal cancer with KRAS G12C: 4

Therapy changed: Divarasib + CetuximabGDC-6036 + Cetuximab.

Tuesday, 15 August 2023 (Version: 20230815AU)

Changed Olaparib in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 1B

References changed: 31157963, 35834777.

Changed Olaparib in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 1B

References changed: 31157963, 35834777.

Monday, 14 August 2023 (Version: 20230814AU)

Removed Atezolizumab in Urothelial carcinoma with TP53+RB1 alterations TP53:Oncogenic mutations AND RB1:Oncogenic mutations, TP53:Oncogenic mutations AND RB1:Deletion: Tier 4

Thursday, 10 August 2023 (Version: 20230810AU)

New Alectinib in Prostate small cell carcinoma with ALK F1174C: 4

Case report. In one case of prostate small cell carcinoma harbouring ALK F1174C, Alectinib led to stable disease for more than 6 months, improved symptoms, and in ctDNA vaf. References: 29559559

Tuesday, 1 August 2023 (Version: 20230801AU)

New Brigimadlin in Well-differentiated liposarcoma, Dedifferentiated liposarcoma with MDM2+TP53 MDM2:Amplification AND NOT TP53:Oncogenic mutations: 3

4 of 7 WDLPS achieved partial response with DCR of 100%. 9 of 12 (75%) of DDLPS achieved disease control. References: 37269344

New Brigimadlin in Cholangiocarcinoma, Pancreatic adenocarcinoma with MDM2+TP53 MDM2:Amplification AND NOT TP53:Oncogenic mutations: 4

Response seen in one case each of cholangiocarcinoma and pancreatic carcinoma in Brightline-1. References: 37269344

Changed Therapy in Dedifferentiated liposarcoma with MDM2+TP53 MDM2:Amplification AND NOT TP53:Oncogenic mutations: 3

Therapy changed: BrigimadlinBI907828.

Changed Therapy in Well-differentiated liposarcoma with MDM2+TP53 MDM2:Amplification AND NOT TP53:Oncogenic mutations: 3

Therapy changed: BrigimadlinBI907828.

Monday, 31 July 2023 (Version: 20230731AU)

New Ivosidenib in Cholangiocarcinoma with IDH1 R132: 1B

TGA approved. Not PBS listed. Phase 3. ClarIDHy trial. Final OS result. In IDH1 mutant cholangiocarcinoma patients, Ivosidenib resulted in median OS of 10.3 months vs 7.5 months (placebo; adjusted for crossover 5.1 months). References: 34554208

New Belzutifan in Hemangioblastoma with VHL Oncogenic mutations (germline): 1B

TGA approved. Not PBS reimbursed. FDA approved. Phase 2. NCT03401788. LITESPARK-004. Updated results. Belzutifan showed antitumor activity in VHL-associated renal cell carcinoma and other neoplasms. Updated results from CNS hemangioblastomas ORR 44%, DCR 90%, time 5.4 months, median PFS was not reached. References: 10.1200/JCO.2023.41.16_suppl.2008

New BGB-3245 in Solid tumour with BRAF V600E, V600K, L597R, G469A, N581Y, G466V, G466E, Class II mutations, Class III mutations, AGK-BRAF fusion: 4

Cell line study. BGB-3245 demonstrates activity against a wide range of BRAF mutations, including both class I and II mutations as well as fusions. References: 10.1158/1538-7445.AM2023-CT031

New Afatinib, Pyrotinib in Non-small cell lung cancer with EGFR V659E: 4

Retrospective study. N=7812. Lung adenocarcinoma with ERBB2 V659E mutation. HER2 inhibitors resulted in longer median PFS compared to chemotherapy. Afatinib and pyrotinib showed stronger binding ability to the HER2 kinase domain. References: 10.1200/JCO.2020.38.15_suppl.e21521

New Pamiparib + AZD7762 in High-grade gliomas with H3F3A G34R, G34V: 4

Preclinical study. Syngeneic pediatric HCC cells harbouring H3.3-G34R mutation showed downregulation of DNA repair pathways, and inhibition of the DDR resulted in accumulation of extrachromosomal DNA and cGAS/STING pathway activation. In mouse models, pamiparib and AZD7762 resulted in long-term survival for approximately 50% of the mice. STING agonist (diABZl) enhanced long-term survivors developing immunological memory. References: 36125896

New Onapristone in Granulosa cell tumour, Low-grade serous ovarian carcinoma, Endometrioid endometrial cancer with PGR Protein expression: 4

Phase 2. NCT03909152. ONA-XR. in PR+ recurrent GCT (cohort 1), LGSOC (cohort 2), and EEC (cohort 3). No objective responses were observed in cohorts 1-3. In cohort 2 (LGSOC), median PFS was 4.4 months, and CBR was 50%. In cohort 1 (GCT), median PFS was 3.5 months, 6-month PFS rate was 30%, and 12-month PFS rate was 20%. CBR was 36%. ONA-XR was well-tolerated. References: 10.1200/JCO.2022.40.16_suppl.5521

Changed Ivosidenib in Cholangiocarcinoma with IDH1 R132

Tier changed: 1B2. Comments changed: TGA approved. Not PBS listed. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months).Not TGA approved. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months)..

Changed Gefitinib in Non-small cell lung cancer with FBXW7 Deletion: R2

Comments changed: Preclinical study. Loss of FBXW7 in NSCLC leads to decreased OS and promotes tumor progression, epithelial-mesenchymal transition, migration, and invasion. Deletion of FBXW7 occurs in a significant proportion of lung adenocarcinomas and squamous cell carcinomas..

Monday, 24 July 2023 (Version: 20230724AU)

Changed Belzutifan in Pancreatic neuroendocrine tumour, Hemangioblastoma with VHL Oncogenic mutations (germline)

Tier changed: 1B3. Comments changed: TGA approved. Not PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas..

Changed Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline)

Tier changed: 1B2. Comments changed: TGA approved. Not PBS listed. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%.Not TGA approved. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%..

Wednesday, 19 July 2023 (Version: 20230719AU)

New Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 2

Phase 3 .LASER301 trial. N=393. In first-line EGFR-mutated NSCLC, Lazertinib showed significantly longer median PFS compared to gefitinib (20.6 vs 9.7 months, HR 0.45, 95% CI 0.34-0.58, P<0.001). PFS benefit observed across all predefined subgroups. ORR similar between Lazertinib versus Gefitinib. Median DOR longer with lazertinib (19.4 months vs 8.3 months). OS at 18-month was higher with lazertinib (80% vs 72%). References: 37379502

New MVC-101 in Solid tumour with EGFR Overexpression, Protein expression: 4

Preclinical study. In vitro and in vivo studies showed TAK-186 resulted in regressions of EGFR-expressing solid tumours. References: 35728872

Tuesday, 18 July 2023 (Version: 20230718AU)

New BI-1810631 in Non-small cell lung cancer with ERBB2 Exon 20 insertion: 3

Beamion Lung 1 . NCT04886804. Preliminary data (N=22) with response seen in 10/22 NSCLC patients with exon 20 insertion, ORR 11 (46%), DCR 23/24 (96%). References: 36528522; JCO.2023.41.16_suppl.8545

New BI-1810631 in Solid tumours with ERBB2 Oncogenic mutations: 4

Beamion Lung 1 . NCT04886804. Preliminary data showed responses seen in oesophageal carcinoma and cholangiocarcinoma. References: 36528522; JCO.2023.41.16_suppl.8545

Removed HMBD-001 in Lung squamous cell carcinoma with alterations : Tier

Friday, 14 July 2023 (Version: 20230714AU)

New Durvalumab in Endometrial cancer with Mismatch repair Deficient: 3

PHAEDRA. Phase 2. ORR in the dMMR cohort was 47% (17 of 36) with median PFS of 8.3 months. References: 34103352

New HMBD-001 in Lung squamous cell carcinoma with TP63 Amplification: 4

References: 10.1158/1538-7445.AM2023-2659

New Durvalumab in Endometrial cancer with Microsatellite Instability Stable, NOT High: R2

PHAEDRA. Phase 2. ORR in the pMMR cohort was 3% (1 of 35) with median PFS of 1.8 months. References: 34103352

New Durvalumab in Endometrial cancer with Mismatch repair Proficient, NOT Deficient: R2

PHAEDRA. Phase 2. ORR in the pMMR cohort was 3% (1 of 35) with median PFS of 1.8 months. References: 34103352

New HMBD-001 in Lung squamous cell carcinoma with :

References:

Changed Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression: 3

References changed: 3727687110.1016/S1470-2045(23)00242-5.

Changed Therapy in Solid tumour with TP53 Oncogenic mutation: 4

Therapy changed: VE-821 + Cisplatin, VE-821.

Thursday, 13 July 2023 (Version: 20230713AU)

New KL590586 in Non-small cell lung cancer, Solid tumours with RET Fusion: 3

Phase 1. NCT05265091. ORR in solid tumour was 60%, 70% and 81% in pretreated and treatment-naive NSCLC respectively. References: JCO.2023.41.16_suppl.3007

Changed Trastuzumab + Tucatinib in Colorectal adenocarcinoma with ERBB2 Amplification, Overexpression: 2

Comments changed: Not TGA approved. FDA approved 19/01/2023. Phase 2. Single-arm study. MOUNTAINEER. NCT03043313. N=84 (Cohort A and B). In metastatic CRC after two-lines of systemic treatment, the tucatinib and trastuzumab combination resulted in ORR of 38% (Cohorts A + B). Median DOR was 12.4 months. Median PFS 8.2 months. Median OS was 24.1 months at follow-up of 20.7 months.Not TGA approved. FDA approved 19/01/2023. Phase 2. Single-arm study. MOUNTAINEER. NCT03043313. N=84. In metastatic CRC after two-lines of systemic treatment, the tucatinib and trastuzumab combination resulted in ORR of 38% (Cohorts A + B). Median DOR was 12.4 months. Median PFS 8.2 months. Median OS was 24.1 months at follow-up of 20.7 months.. References changed: 37142372, 10.1016/j.annonc.2022.04.440.

Tuesday, 11 July 2023 (Version: 20230711AU)

New RLY-4008 in Cholangiocarcinoma with FGFR2 Fusion, C382R, R678H, H167_N173del, C383R, W290C: 3

Phase 1/2.ReFocus. NCT04526106. ORR in FGFR2-Mutated cholangiocarcinoma was 29%. In the cohort with an FGFR2 fusion and a dosage of 70mg or higher, the ORR was 73% (8/11). In FGFRi refractory CCA, the ORR was 21% (3/14). References: 10.1200/JCO.2023.41.16_suppl.4009

New Ceralasertib in Chronic lymphocytic leukaemia with ATM Oncogenic mutation: 4

Cell line and xenograft study. AZD6738 induce cell death in CLL cell lines and primary cells with TP53 or ATM defects, where inhibition of ATR signaling led to the accumulation of unrepaired DNA damage and cell death by mitotic catastrophe in TP53- or ATM-defective CLL cells. AZD6738 sensitized TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. References: 26563132

New Ceralasertib + Chlorambucil, Ceralasertib + Fludarabine, Ceralasertib + Bendamustine, Ceralasertib + Ibrutinib in Chronic lymphocytic leukaemia with ATM Oncogenic mutation: 4

Cell line and xenograft study. AZD6738 sensitises TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. References: 26563132

New VE-821 + Cisplatin in Solid tumour with ATM Oncogenic mutation: 4

Cell line study. ATR inhibition Is synthetic lethal with the ATM-p53 tumor pathway when cells are exposed to DNA-damaging agents. References: 21490603

New Ceralasertib in Chronic lymphocytic leukaemia with TP53 Oncogenic mutation: 4

Cell line and xenograft study. AZD6738 induce cell death in CLL cell lines and primary cells with TP53 or ATM defects, where inhibition of ATR signaling led to the accumulation of unrepaired DNA damage and cell death by mitotic catastrophe in TP53- or ATM-defective CLL cells. AZD6738 sensitized TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. References: 26563132

New Ceralasertib + Chlorambucil, Ceralasertib + Fludarabine, Ceralasertib + Bendamustine, Ceralasertib + Ibrutinib in Chronic lymphocytic leukaemia with TP53 Oncogenic mutation: 4

Cell line and xenograft study. AZD6738 sensitises TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. References: 26563132

New VE-821 + Cisplatin in Solid tumour with TP53 Oncogenic mutation: 4

Cell line study. ATR inhibition Is synthetic lethal with the ATM-p53 tumor pathway when cells are exposed to DNA-damaging agents. References: 21490603

New Berzosertib + Irinotecan in Gastric cancer, Gastroesophageal junction adenocarcinoma with TP53 Oncogenic mutation: R2

Phase 2 . NCT03641313. In patients with TP53-mutated gastric and gastro-esophageal junction adenocarcinoma, irinotecan and berzosertib did not meet the primary endpoint of ORR of 6% (1/16). Median PFS 4.0 months. Median overall OS 6.2 months. References: 10.1200/JCO.2023.41.16_suppl.4044

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations

Tier changed: 1B.

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations

Tier changed: 1B.

Changed Patritumab deruxtecan in Breast cancer with ERBB2 NOT Amplification and NOT Overexpression: 3

References changed: 10.1200/JCO.2023.41.16_suppl.100410.1200/JCO.2022.40.16_suppl.9017.

Wednesday, 5 July 2023 (Version: 20230705AU)

New Erdafitinib in Urothelial carcinoma with FGFR2 Fusion, Oncogenic mutations: 2

Phase 3. THOR. Compared with chemotherapy, erdafitinib achieved a median PFS 5.6 months (v 2.7 months. HR 0.58) and OS (12.1 v 7.8 months, HR 0.64).ORR was 46 vs 12 %. References: 10.1200/JCO.2023.41.17_suppl.LBA4619

New Erdafitinib in Urothelial carcinoma with FGFR3 Fusion, Oncogenic mutations: 2

Phase 3. THOR. Compared with chemotherapy, erdafitinib achieved a median PFS 5.6 months (v 2.7 months. HR 0.58) and OS (12.1 v 7.8 months, HR 0.64).ORR was 46 vs 12 %. References: 10.1200/JCO.2023.41.17_suppl.LBA4619

Tuesday, 4 July 2023 (Version: 20230704AU)

New Crizotinib, Crizotinib + Cetuximab in Colorectal adenocarcinoma with MET Amplification: 4

Xenograft models. MET inhibitors could be effective in overcoming the resistance caused by MET amplification associated with anti-EGFR therapy. References: 23729478

New Tepotinib + Cetuximab in Colorectal adenocarcinoma with MET Amplification: 4

References: NCT04515394

New VT104 in Mesothelioma with NF2 Oncogenic mutation, Deletion: 4

References: 33850002

New Talazoparib in Myelodysplastic syndrome, Acute myeloid leukaemia with RAD21 Oncogenic mutations: 4

Cell line study. Inactivation of SMC3 or RAD21, and STAG2 mutations, increase sensitivity to PARP inhibition. References: 33351783

New Talazoparib in Myelodysplastic syndrome, Acute myeloid leukaemia with SMC3 Oncogenic mutations: 4

Cell line study. Inactivation of SMC3 or RAD21, and STAG2 mutations, increase sensitivity to PARP inhibition. References: 33351783

New Talazoparib in Myelodysplastic syndrome, Acute myeloid leukaemia with STAG2 Oncogenic mutations: 4

Cell line study. STAG2-mutant cells have increased DNA damage and are sensitive to PARP inhibition, suggesting that targeting DNA damage repair pathways may be a potential therapeutic strategy for cohesin-mutant malignancies including MDS/AML. References: 33351783

New Palbociclib in Gastric cancer, Gastroesophageal junction adenocarcinoma with CCND1 Overexpression: R2

Phase 2. NCT01037790. In patients with previously treated gastroesophageal cancers and CCND1 overexpression, palbociclib monotherapy demonstrated minimal clinical activity and no objective responses were seen. References: 32692450

New Cetuximab, Panitumumab in Colorectal adenocarcinoma with MET Amplification: R2

Amplification of the MET gene is associated with acquired resistance to EGFR targeted therapy in patients with metastatic colorectal cancer; MET inhibitors could be effective in overcoming this resistance. References: 23729478

New Cetuximab, Panitumumab in Colorectal adenocarcinoma with MET Amplification: R2

MET amplification is rare in primary colorectal cancer but occurs in a significant number of patients who are refractory to anti-EGFR therapy identified through circulating-free DNA. References: 27421137

Changed Atezolizumab in Urothelial carcinoma with TP53+RB1 : 4

Alterations changed: TP53:Oncogenic mutations AND RB1:Oncogenic mutations, TP53:Oncogenic mutations AND RB1:Deletion.

Tuesday, 27 June 2023 (Version: 20230627AU)

New PLX9486 in Gastrointestinal stromal tumour with KIT Exon 11 mutation, Exon 11 deletion, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829P: 4

References: 34236401

New PLX9486 in Gastrointestinal stromal tumour with KIT NOT Oncogenic mutations, V654A, T670I: R2

References: 34236401

Friday, 23 June 2023 (Version: 20230623AU)

New GB263T in Non-small cell lung cancer with EGFR Oncogenic mutation, Exon 20 insertion, C797S: 4

Cell line study. References: 10.1158/1538-7445.AM2022-LB538

New Trastuzumab + Carboplatin in Ovarian mucinous carcinoma with ERBB2 Amplification, Overexpression: 4

Case report. A significant response was observed in this case report of mucinous carcinoma with HER2 overexpression and amplification when treated with trastuzumab and carboplatin therapy. References: 20003286

New GB263T in Non-small cell lung cancer with MET Amplification, Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 4

Cell line study. References: 10.1158/1538-7445.AM2022-LB538

New Osimertinib, Gefitinib in Non-small cell lung cancer with FGFR2 Fusions, FGFR2-CCDC6 fusion, FGFR2-KIAA1598 fusion, FGFR2-TACC2 fusion: R2

References: 35566609

New Osimertinib, Gefitinib in Non-small cell lung cancer with FGFR3 FGFR3-TACC3 fusion: R2

References: 35566609

Changed Trastuzumab deruxtecan with ERBB2 Overexpression, Protein expression: 3

Cancer type(s) changed: Cervical cancer, Endometrial cancer, Ovarian cancer, Bladder cancer, Solid tumours except Pancreatic adenocarcinoma, Biliary tract cancersCervical cancer, Endometrial cancer, Ovarian cancer, Bladder cancer, Solid tumours except Panceratic cancer and Biliary tract cancer

Changed Therapy in Prostate cancer with PIK3R1 Oncogenic mutation, Deletion: 4

Therapy changed: Ipatasertib, MK-2206.

Thursday, 22 June 2023 (Version: 20230622AU)

New Trastuzumab deruxtecan in Biliary tract cancer with ERBB2 Overexpression: 3

Phase 2. NCT04482309. DESTINY-PanTumor02. ORR in biliary. References: 10.1200/JCO.2023.41.17_suppl.LBA3000

New Trastuzumab deruxtecan in Cervical cancer, Endometrial cancer, Ovarian cancer, Bladder cancer, Solid tumours except Panceratic cancer and Biliary tract cancer with ERBB2 Overexpression, Protein expression: 3

Phase 2. NCT04482309. DESTINY-PanTumor02. References: 10.1200/JCO.2023.41.17_suppl.LBA3000

New Buparlisib + Letrozole, Alpelisib + Letrozole in Breast cancer with MAP3K1+PIK3CA MAP3K1:Oncogenic mutations AND PIK3CA:Oncogenic mutations: 4

Retrospective study from MSK-IMPACT. The clinical benefit associated with combined PI3K and ER inhibition in ER+ breast cancer harbouring MAP3K1 alteration, which may be associated with luminal A status. References: 31552290

New Ipatasertib in Prostate cancer with PIK3R1 Oncogenic mutation, Deletion: 4

Cell line study. PIK3R1-mutant and knockdown prostate cancer cells are sensitive to AKT inhibitors, which have shown sensitivity of to the AKT kinase inhibitors. References: 35670774

New Trastuzumab deruxtecan in Pancreatic adenocarcinoma with ERBB2 Overexpression, Protein expression: R2

Phase 2. NCT04482309. DESTINY-PanTumor02. References: 10.1200/JCO.2023.41.17_suppl.LBA3000

Removed ERBB2 inhibitor in Breast cancer with ERBB2 alterations Oncogenic mutations: Tier 4

Changed Futibatinib in Solid tumours with FGFR1 N546D: 4

Comments changed: Phase I trial. NCT02052778. FOENIX-101. N = 86. Futibatinib, a selective FGFR1-4 inhibitor, was evaluated in patients with refractory solid tumors with partial responses observed in FGFR2 fusion-positive intrahepatic cholangiocarcinoma (n = 3) and FGFR1-mutant primary brain tumor (n = 2).FOENIX-101. ORR 11% in qd cohort.

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody with MLH1 Loss-of-function mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaSolid tumours

Changed Tazemetostat in Ovarian small cell carcinoma with SMARCA2+SMARCA4 SMARCA2:Loss of protein expression and SMARCA4:Loss of protein expression: 4

Comments changed: Cell lines and xenograft study. Inhibition of EZH2 by Tazemetostat selectively kills small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) cells deficient in SMARCA2 and SMARCA4..

Changed Palbociclib, Ribociclib, Abemaciclib in Solid tumours with FAT1 Loss-of-function mutations: R2

Comments changed: Preclinical study. Loss-of-function mutations in FAT1 led to increased CDK6 expression, and suppressing CDK6 restored sensitivity to CDK4/6i. The induction of CDK6 was mediated by the Hippo pathway, with YAP and TAZ transcription factors accumulating on the CDK6 promoter. Alterations in other Hippo pathway components also contributed to CDK4/6i resistance..

Saturday, 17 June 2023 (Version: 20230617AU)

Changed Vorasidenib with IDH1 Oncogenic mutation: 2

Cancer type(s) changed: Low-grade gliomas

Changed Depatuxizumab mafodotin in Glioma, Glioblastoma with EGFR vIII: 4

Comments changed: Phase 2. M12-356. NCT01800695. EGFR-amplified, recurrent glioblastoma. N=66. Depatuxizumab mafodotin resulted in ORR of 7% with 6-month PFS rate of 29%..

Changed Bemarituzumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with FGFR2 Overexpression, amplification: 4

Comments changed: Phase 1. Confirmed partial response in 5/28 (18%) of patients with high FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma..

Changed Tazemetostat in Rhabdoid tumors with SMARCB1 Oncogenic mutations: 4

Comments changed: Phase 1. NCT02900664. In children with genetically altered malignant rhabdoid tumors (MRTs) or atypical teratoid rhabdoid tumors (ATRTs), inhibition of EZH2 with a small-molecule inhibitor led to durable tumor regression. The inhibitor induced apoptosis and differentiation specifically in SMARCB1-deleted MRT cells. Treatment in xenograft-bearing mice resulted in dose-dependent regression of MRTs and prevention of tumor regrowth after dosing cessation..

Changed Palbociclib, Ribociclib, Abemaciclib in Breast cancer with CCNE1 Amplification: R2

Comments changed: Phase 3 PALOMA-3 trial. Gene expression analysis identified that patients with high CCNE1 mRNA expression had lower efficacy with palbociclib compared to those with low CCNE1 expression. High CCNE1 mRNA expression was associated with relative resistance to palbociclib..

Changed PD173074 in Colorectal cancer with FGFR1 Amplification: R2

Comments changed: Retrospective exploratory and cell line studies. In 764 surgically resected colorectal cancers, FGFR1 amplification was found in 3-7 of CRCs. FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, and associated with inferior progression-free survival. PD173074 repressed the proliferation of a CRC cell line overexpressing FGFR1 but not cells with FGFR1 amplification.Cell line study.

Changed Rucaparib, Niraparib in Ovarian cancer with RAD51C Loss of promoter methylation: R2

Comments changed: Preclinical study. In high-grade ovarian cancer, homozygous RAD51C promoter methylation predicts sensitivity to PARP inhibitors. Single unmethylated gene copy confers resistance to PARP inhibitors..

Wednesday, 14 June 2023 (Version: 20230614AU)

New Patritumab deruxtecan in Breast cancer with ERBB2 NOT Amplification and NOT Overexpression: 3

NCT04699630. Phase 2. N=60. In HER2-negative metastatic breast cancer, HER3-DXD resulted in ORR of 35% for all pts with CBR of 48%. Response are seen irrespective of HER3 expression status. References: 10.1200/JCO.2022.40.16_suppl.9017

New Camonsertib in Ovarian cancer, Pancreatic adenocarcinoma, Non-small cell lung cancer with ATM Oncogenic mutations, Oncogenic mutations (germline): 4

Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations. References: 37277454

New Camonsertib in Solid Tumours, Ovarian cancer, Head and neck squamous cell carcinoma, with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 4

Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations. References: 37277454

New Camonsertib in Melanoma with BRCA2 Oncogenic mutations: 4

Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations. References: 37277454

New Camonsertib in Prostate cancer with CDK12 Oncogenic mutations: 4

Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations. References: 37277454

New Camonsertib in Ovarian cancer with RAD51C Oncogenic mutations, Oncogenic mutations (germline): 4

Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations. References: 37277454

New Camonsertib in Ovarian cancer with SETD2 Oncogenic mutations: 4

Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations. References: 37277454

New Atezolizumab in Urothelial carcinoma with TP53+RB1 TP53:Oncogenic mutations AND RB1:Oncogenic mutations: 4

Retrospective study. Somatic co-alterations of RB1 and TP53 genes in muscle invasive urothelial bladder carcinoma may be associated with responsiveness to immunity checkpoint inhibitors, correlating with tumour mutational burden (TMB) tumor microenvironment metascore (TMM). References: 33879103

Changed Vorasidenib in Low-grade glioma with IDH1 Oncogenic mutation: 2

Comments changed: Phase 3. NCT04164901. INDIGO. N=331. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26)Phase 3. NCT04164901. INDIGO. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26).

Changed Vorasidenib in Low-grade glioma with IDH2 Oncogenic mutation: 2

Comments changed: Phase 3. NCT04164901. INDIGO. N=331. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26)Phase 3. NCT04164901. INDIGO. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26).

Changed Nab-sirolimus in Perivascular epithelioid cell tumour with TSC2 : 2

Alterations changed: Loss-of-function mutations, Oncogenic mutations.

Monday, 5 June 2023 (Version: 20230605AU)

New Vorasidenib in Low-grade glioma with IDH1 Oncogenic mutation: 2

Phase 3. NCT04164901. INDIGO. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26). References: 10.1056/NEJMoa2304194

New Vorasidenib in Low-grade glioma with IDH2 Oncogenic mutation: 2

Phase 3. NCT04164901. INDIGO. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26). References: 10.1056/NEJMoa2304194

New Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression: 3

Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months. References: 10.1016/S1470-2045(23)00242-5

New AMB-05X in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 4

References: 10.1016/j.annonc.2022.07.1589

Changed Pyrotinib in Non-small cell lung cancer with ERBB2 D769Y, D742N: 4

Comments changed: Case report. ERBB2 D769Y and D742N mutations are sensitive to pyrotinib, showing partial response to treatment with the combination of gefitinib and pyrotinib overcoming HER2-mediated resistance to gefitinib.The case report cannot confirm dual driver.

Wednesday, 24 May 2023 (Version: 20230524AU)

New Encorafenib + Osimertinib in Non-small cell lung cancer with EGFR EGFR:exon 19 deletion and BRAF:V600E: 4

Cell line study. Combining osimertinib with a BRAF V600E inhibitor had a significant inhibitory effect in a patient derived cell line model. References: 27923714

New Osimertinib in Non-small cell lung cancer with EGFR EGFR:exon 19 deletion and BRAF:V600E: R2

Cell line study. Combining osimertinib with a BRAF V600E inhibitor had a significant inhibitory effect in a patient derived cell line model. References: 27923714

Saturday, 20 May 2023 (Version: 20230520AU)

Changed Sotorasib in Non-small cell lung cancer with KRAS G12C

Tier changed: 1B2. Comments changed: TGA provisional approval. Not PBS reimbursed. FDA approved for second-line and beyond. Phase 2 CODEBREAK100. Previously treated patients. ORR 37%. PFS 6.8mo. OS 12.5mo.Not TGA approved. FDA approved for second-line and beyond. Phase 2 CODEBREAK100. Previously treated patients. ORR 37%. PFS 6.8mo. OS 12.5mo..

Friday, 19 May 2023 (Version: 20230519AU)

New BI-1701963 in Solid tumour with KRAS Oncogenic mutations: 4

NCT04111458. References: 10.1016/j.annonc.2021.08.1046

Changed TYRA-300 in Solid tumours with FGFR3 : 4

Alterations changed: Fusions, FGFR3-TACC3 fusion, V555M, V555L, V555G, V555K, K650M, K650E, Oncogenic mutations, S249C, R248C, Y373C, G370CFusions, V555M, V555L.

Wednesday, 10 May 2023 (Version: 20230510AU)

New Cetuximab, Panitumumab, Cetuximab + FOLFIRI, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab, Fluorouracil + Panitumumab in Colorectal adenocarcinoma with EGFR S492R: R2

Retrospective analysis of patients with available samples from ASPECCT showed that 16% of patients in the cetuximab and 1% of patients in the panitumumab developed treatment-emergent EGFR S492R mutation. References: 10.1200/jco.2015.33.3_suppl.740, 33026965

Tuesday, 9 May 2023 (Version: 20230509AU)

New Dabrafenib + Trametinib in Anaplastic thyroid cancer, Biliary tract cancer, Small intestine adenocarcinoma, Low-grade glioma, High-grade glioma, Hairy cell leukaemia, Multiple myeloma with BRAF V600E: 2

Phase 2 basket trial. ROAR. NCT02034110. Rare cancer cohort. ORR was 56% for anaplastic thyroid carcinoma (PFS 6.7 months), 53% for biliary tract cancer (PFS 9.0 months), 67% for small intestine adenocarcinoma, 54% for low-grade glioma (PFS 9.5 months), 33% for high-grade glioma (PFS 5.5 months), 89% for hairy cell leukemia, and 50% for multiple myeloma (PFS 6.3 months). References: 37059834

Sunday, 7 May 2023 (Version: 20230507AU)

New Aumolertinib in Non-small cell lung cancer with EGFR C797S: R2

The most common mechanisms of resistance to Aumolertinib were acquired EGFR C797S mutation and aberration in PIK3CA bypass track. References: 10.1016/j.jtho.2022.07.739

New Aumolertinib in Non-small cell lung cancer with PIK3CA Oncogenic mutations: R2

The most common mechanisms of resistance to Aumolertinib were acquired EGFR C797S mutation and aberration in PIK3CA bypass track. References: 10.1016/j.jtho.2022.07.739

Friday, 5 May 2023 (Version: 20230505AU)

New Pemigatinib in Endometrial cancer with FGFR1 Fusion: 3

Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016

New Pemigatinib in Cervical cancer with FGFR2 C382R: 3

Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016

New Pemigatinib in Cholangiocarcinoma with FGFR2 C382R, I291_Y308del, Extracellular domain deletion, Y375C, W290C: 3

Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016

New Pemigatinib in Ovarian cancer, Pancreatic adenocarcinoma, Cervical cancer, Non-small cell lung cancer, Prostate cancer with FGFR2 Fusion: 3

Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016

New Pemigatinib in Glioblastoma, Diffuse astrocytoma, Cervical cancer with FGFR3 Fusion; K656E: 3

Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016

New Pemigatinib in Urothelial carcinoma with FGFR3 Y373C: 3

Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016

New LY3410738 in Acute myeloid leukaemia with IDH1 R132: 3

Phase 1. NCT04603001. Dose escalation IDH1/2m R/R AML. Responses were observed in both IDH1m and IDH2m AML. References: 10.1158/1538-7445.AM2023-CT026

New LY3410738 in Acute myeloid leukaemia with IDH2 R172, R140: 3

Phase 1. NCT04603001. Dose escalation IDH1/2m R/R AML. Responses were observed in both IDH1m and IDH2m AML. References: 10.1158/1538-7445.AM2023-CT026

New IBI351 in Non-small cell lung cancer with KRAS G12C: 3

Phase 1. NCT05005234. N=67. NSCLC across all dose levels, the confirmed ORR was 45%, and DCR was 93%. References: 10.1158/1538-7445.AM2023-CT030

New Lifirafenib + Mirdametinib in Low-grade serous ovarian cancer with KRAS Oncogenic mutations: 3

Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. ORR in low-grade serous ovarian cancer was (59%). DCR was 94%. References: 10.1158/1538-7445.AM2023-CT033

New BGB-3245 in Endometrial cancer with BRAF K601E: 4

Phase 1. NCT04249843. Response seen in a patient with endometrial cancer harbouring BRAF K601E mutation. References: 10.1158/1538-7445.AM2023-CT031

New BGB-3245 in Melanoma, Low-grade serous ovarian cancer, Cholangiocarcinoma with BRAF V600E: 4

Phase 1. NCT04249843. Responses seen in patients post-BRAF/MEK inhibitor. References: 10.1158/1538-7445.AM2023-CT031

New Lifirafenib + Mirdametinib in Non-small cell lung cancer with BRAF V600E: 4

Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. References: 10.1158/1538-7445.AM2023-CT033

New Exarafenib in Solid tumour with BRAF V600E, Class II mutations, Class III mutations: 4

References: 10.1158/1538-7445.AM2023-CT032

New Lifirafenib + Mirdametinib in Endometrial cancer with BRAF ZC3HAV1-BRAF fusion: 4

Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. References: 10.1158/1538-7445.AM2023-CT033

New Lifirafenib + Mirdametinib in Endometrial cancer with KRAS G12A: 4

Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. References: 10.1158/1538-7445.AM2023-CT033

New GDC-6036 + Cetuximab in Colorectal cancer with KRAS G12C: 4

Phase 1b. NCT04449874. Confirmed ORR of 62% (18/29). Ongoing study. References: 10.1158/1538-7445.AM2023-CT029

New LY3537982 in Colorectal cancer, Pancreatic adenocarcinoma, Solid tumours with KRAS G12C: 4

Phase 1. NCT04956640. ORR was 7% (1/17) in CRC, 3/8 (38%) in pancreatic, and 4/15 (36%) in other solid tumorus. References: 10.1158/1538-7445.AM2023-CT028

New LY3537982 in Non-small cell lung cancer with KRAS G12C: 4

Phase 1. NCT04956640. ORR 3/5 (60%) in KRAS G12C inhibitor treatment naive NSCLC. References: 10.1158/1538-7445.AM2023-CT028

New BGB-3245 in Appendiceal cancer with KRAS G12D: 4

Phase 1. NCT04249843. Response seen in a patient with appendiceal cancer harbouring KRAS G12D mutation. References: 10.1158/1538-7445.AM2023-CT031

New VT3989 in Mesothelioma, Sarcoma with NF2 Oncogenic mutations: 4

NCT04665206. Phase 1. N=67. Responders (2 refractory mesothelioma and 1 NF2 mutant sarcoma) were seen with response by targeting the Hippo-YAP-TEAD pathway. References: 10.1158/1538-7445.AM2023-CT006

New BGB-3245 in Melanoma with NRAS G12S, Q61K: 4

Phase 1. NCT04249843. Response seen in a patient post-BRAF/MEK inhibitor. References: 10.1158/1538-7445.AM2023-CT031

New Exarafenib in Melanoma with NRAS Oncogenic mutations: 4

References: 10.1158/1538-7445.AM2023-CT032

New Lifirafenib + Mirdametinib in Non-small cell lung cancer with NRAS Q61K: 4

Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. References: 10.1158/1538-7445.AM2023-CT033

Changed Adagrasib in Solid tumours, Pancreatic adenocarcinoma, Appendiceal carcinoma, Cholangiocarcinoma, Endometrial carcinoma with KRAS G12C: 3

References changed: 37099736, 10.1200/JCO.2023.41.36_suppl.425082.

Changed GDC0623, PD0325901, Trametinib, Selumetinib, LY3009120 in Melanoma with BRAF Fusions, FKBP15-BRAF fusion, TARDBP-BRAF fusion, AGK-BRAF fusion, SKAP2-BRAF fusion, CUL1-BRAF fusion, KIAA1549-BRAF fusion: 4

Comments changed: Cell line study. This study investigated the heterogeneous responses of six melanoma cell lines harboring BRAF fusions to RAF and MEK inhibitors. Higher expression level was correlated with resistance and fusion partners containing a dimerization domain promoted paradoxical activation of the MAPK pathway and hyperproliferation. AlphaC-IN/DFG-OUT RAF inhibitors blunted paradoxical activation and had increased therapeutic efficacy in vitro and in vivo when combined with MEK inhibitors..

Sunday, 30 April 2023 (Version: 20230430AU)

New Ibrutinib in Waldenstroms macroglobulinaemia with CXCR4 S338X: R2

Reduced response rate compared with CXCR4 WT patients. References: 32931398, 31570491

New Ivosidenib in Acute myeloid leukaemia with FLT3 Internal tandem duplication: R2

RTK pathway mutations are associated with primary resistance to ivosidenib. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with IDH1 S280F, R119P, G131A, D279N, G289D, H315D: R2

2-HG restoration as a result of mutations preventing drug/cofactor binding and/or emergence of an IDH2 mutation represents a mechanism of secondary resistance. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with IDH2 R140Q, R172K: R2

2-HG restoration as a result of mutations preventing drug/cofactor binding and/or emergence of an IDH2 mutation represents a mechanism of secondary resistance. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with NRAS Oncogenic mutations: R2

NRAS- reduced response rate compared with WT NRAS. References: 32380538

Changed Gilteritinib in Acute myeloid leukaemia with FLT3 D835, I836, Internal tandem duplication

Tier changed: 1B. Comments changed: PBS reimbursed in R/R FLT3-mutant AMLTGA approved. Not PBS reimbursed.

Changed Ruxolitinib in Myelofibrosis with JAK2 V617F: 1

Comments changed: PBS reimbursed for intermediate-1 or higher risk myelofibrosis, but not dependent on JAK status. COMFORT-I..

Changed Enasidenib in Acute myeloid leukaemia with IDH2 R140Q, R172K, R172S: 1B

Comments changed: TGA approved. Not PBS reimbursed. For relapsed/refractory AML..

Changed Ivosidenib in Acute myeloid leukaemia with IDH1 R132: 2

Comments changed: Not TGA approved. FDA approved..

Friday, 28 April 2023 (Version: 20230428AU)

Changed Ceralasertib + Olaparib in Ovarian cancer with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 3

Comments changed: Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 50% (6/12).Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).. References changed: 37097611, 10.1200/JCO.2021.39.15_suppl.5516.

Friday, 21 April 2023 (Version: 20230421AU)

New Adagrasib in Solid tumours, Pancreatic adenocarcinoma, Appendiceal carcinoma, Cholangiocarcinoma, Endometrial carcinoma with KRAS G12C: 3

Not TGA approved. Not FDA approved. Phase 1/2. KRYSTAL-1. N=57. NCT03785249. Adagrasib 600mg BD. ORR was 35% (20/57). DCR was 86%. Median DOR was 5.3 months. ORR was 33% in PDAC subgroup and 42% in BTC. Median PFS was 7.4 months. References: 10.1200/JCO.2023.41.36_suppl.425082

Changed Crizotinib, Entrectinib, Loratinib with ROS1 G2032R: R2

Cancer type(s) changed: Solid tumours

Thursday, 20 April 2023 (Version: 20230420AU)

New Zenocutuzumab in Breast cancer with NRG1 SLC3A2-NRG1 fusion: 4

References: 35977350

New Afatinib, Trastuzumab in Colorectal adenocarcinoma with ERBB2 ERBB2-GRB7 fusion: R2

References: 26660078

New Trastuzumab in Colorectal adenocarcinoma with ERBB2 ERBB2-GRB7 fusion: R2

Case report. Retrospective series. Acquired ERBB2-GRB7 fusion in the follow-up was identified on liquid biopsy. References: 36470901

New Cetuximab, Panitumumab in Colorectal adenocarcinoma with MAP2K1 K757E, K57N: R2

References: 26660078

Changed Trastuzumab, Ado-Trastuzumab Emtansine in Gastric cancer with ERBB2 : 4

Alterations changed: MDK-ERBB2 fusion, Fusions.

Wednesday, 19 April 2023 (Version: 20230419AU)

New Trametinib in Solid tumour except Uveal melanoma with GNA11 Oncogenic mutations; Q209L: R2

Phase 2. NCI-MATCH. NCT02465060. EAY131. In GNA11/GNAQ cohort, 1 of 4 responder was seen (melanoma). Overall, however, trametinib did not demonstrate meaningful clinical activity. References: 37053535

New Trametinib in Solid tumour except Uveal melanoma with GNAQ Oncogenic mutations: R2

Phase 2. NCI-MATCH. NCT02465060. EAY131. In GNA11/GNAQ cohort, 1 of 4 responder was seen (melanoma). Overall, however, trametinib did not demonstrate meaningful clinical activity. References: 37053535

New Trametinib in Solid tumour with NF1 Oncogenic mutations: R2

Phase 2. NCI-MATCH. NCT02465060. EAY131. In NF1 cohort, ORR was 4% (2 responders in 46 patients). PFS was 1.9 months. References: 37053535

Friday, 14 April 2023 (Version: 20230414AU)

New Pralsetinib in Medullary thyroid cancer with RET Exon 10 deletion; V591_607del: 4

Case report of significance response to Pralsetinib in a MTC patient harbouring two VUS L1016S and in-frame deletion in exon 10. References: 36053791

New Taletrectinib, Repotrectinib, NVL-520 in Solid tumour with ROS1 G2032R: 4

References: 36511802

New Crizotinib, Entrectinib, Loratinib, Taletrectinib, Repotrectinib, NVL-520 in Solid tumour with ROS1 SLC34A2-ROS1 fusion, EZR-ROS1 fusion, CD74-ROS1 fusion, GOPC-ROS1 fusion, CEP85L-ROS1 fusion: 4

Cell-line study. References: 36511802

New Crizotinib, Entrectinib, Loratinib in Solid tumour with ROS1 G2032R: R2

References: 36511802

Wednesday, 12 April 2023 (Version: 20230412AU)

New Neratinib in Breast cancer with ERBB2 L869R: 4

Case report of a lobular breast carcinoma harboring ERBB2 L869R is sensitive to Neratinib with clinical response. References: 28274957

New Olaparib in Acute myeloid leukaemia with SRSF2 P95H: 4

Cell line study. Mutation in spliceosomes causes accumulation of R-loops in cells, triggering a PARP1 response. PARP inhibition with Olaparib has shown to prolong survival in murine model of myeloid leukaemia harbouring SRSF2 P95H mutation. References: 10.1158/1538-7445.AM2023-6183

New Olaparib in Acute myeloid leukaemia with U2AF1 S34F: 4

Cell line study. Mutation in spliceosomes causes accumulation of R-loops in cells, triggering a PARP1 response. PARP inhibition with Olaparib has shown to prolong survival in murine model of myeloid leukaemia harbouring SRSF2 P95H mutation. References: 10.1158/1538-7445.AM2023-6183

New Neratinib in Breast cancer with ERBB2 T798I: R2

Case report. ERBB2 T798I gatekeeper mutation was found in a breast cancer patient after sustained partial response to neratinib. References: 28274957

Sunday, 9 April 2023 (Version: 20230409AU)

Changed Ipatasertib in Solid tumoursE17K: 3

Biomarker changed: AKT1.

Changed Osimertinib + Navitoclax in Non-small cell lung cancerEGFR:Oncogenic mutations and RBM10:Loss-of-function mutations: 4

Biomarker changed: EGFR+RBM10EGFR+RMB10.

Saturday, 8 April 2023 (Version: 20230408AU)

New Osimertinib + Navitoclax in Non-small cell lung cancer with EGFR+RMB10 EGFR:Oncogenic mutations and RBM10:Loss-of-function mutations: 4

Preclinical study. In RBM10-loss xenograft models, adding BH3-mimetic to Osimertinib leads to restored apoptosis in EGFR-mutant cells that have a RBM10-null condition. References: 35579943

New Olaparib in Osteosarcoma with Mutational signature SBS3 signature: 4

Case report. Prolonged complete response in radiotherapy-associated osteosarcoma with biallelic FANCM loss, high HRD score, and SBS3 mutational signature. References: 36848605

New Osimertinib in Non-small cell lung cancer with RBM10 Loss-of-function mutations: R2

Preclinical and retrospective observational study. RBM10 loss is associated with reduced response to Osimretinib in EGFR-mutant non-small cell lung cancer models and cohort. References: 35579943

Wednesday, 5 April 2023 (Version: 20230405AU)

New Osimertinib + Pemetrexed in Non-small cell lung cancer with EGFR EGFR-SEPT14 Fusion: 4

Case report of a NSCLC leptomeningeal metastasis harbouring EGFR-SEPT14 osimertinib with intrathecal pemetrexed. References: 34486539

New Erlotinib, Lapatinib in Glioblastoma with EGFR vIII, EGFR-SEPT14 fusion: 4

Xenograft model. References: 23917401

Friday, 31 March 2023 (Version: 20230331AU)

New Trastuzumab deruxtecan in Non-small cell lung cancer with RB1 Oncogenic mutations: R2

Case series. The emergence of acquired resistance to trastuzumab deruxtecan in TP53-/HER2-mutated non-small-cell lung cancer may be correlated with the loss of Rb1. References: 36809053

Thursday, 30 March 2023 (Version: 20230330AU)

New Niraparib + Abiraterone Acetate in Prostate cancer with BRCA1 Oncogenic mutations: 2

Phase 3. MAGNITUDE. NCT03748641. First-line metastatic prostate cancer. In the BRCA1/2 subgroup, median radiological PFS was longer in the niraparib + abiraterone group compared to abiraterone alone (16.6 v 10.9 months). In contrast, non-BRCA1/2 but HR-positive group (comprising ATM, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) did not show prolonged radiologic PFS (HR 0.99). References: 36952642

New Niraparib + Abiraterone Acetate in Prostate cancer with BRCA2 Oncogenic mutations: 2

Phase 3. MAGNITUDE. NCT03748641. First-line metastatic prostate cancer. In the BRCA1/2 subgroup, median radiological PFS was longer in the niraparib + abiraterone group compared to abiraterone alone (16.6 v 10.9 months). In contrast, non-BRCA1/2 but HR-positive group (comprising ATM, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) did not show prolonged radiologic PFS (HR 0.99). References: 36952642

New Trastuzumab deruxtecan in Uterine carcinosarcoma with ERBB2 Protein expression, Low protein expression: 3

NCCH1615/STATICE. Phase 2. Single-arm. ORR were 55% (12/22) in HER2-high and 70% (7/10) in HER2-low group. Median PFS were 6.9 and 8.1 months respectively. HER2-low status is defined as IHC 1+/2+. HER2-High is defined as IHC 3+. References: 36977309

New Naporafenib + Trametinib in Melanoma with NRAS Oncogenic mutations: 3

Phase 1B. NCT02974725. ORR for the Naporafenib 200mg BD and Trametinib 1mg QD group group was 7/15 (47%) and 2/15 (13%) for the Naporafenib 400mg BD and Trametinib 0.5mg QD group. Overall DCR was 73% in 30 patients. References: 36947734

New YH32367 in Solid tumours with ERBB2 Protein expression, Overexpression, Amplification: 4

References: 10.1016/j.annonc.2021.08.1066

New Ficlatuzumab + Cetuximab in Head and neck squamous cell carcinoma with Human Papillomavirus Status Negative: 4

NCT03422536. In treatment refractory HPV-negative HNSCC, patients in the Ficlatuzumab + Cetuximab combination arm resulted in ORR of 38% (6/16) with median PFS of 4.1 months. References: 36977289

New Ficlatuzumab + Cetuximab in Head and neck squamous cell carcinoma with MET Overexpression: 4

NCT03422536. In treatment refractory HNSCC, patients in the Ficlatuzumab + Cetuximab combination arm resulted in significant hazard reduction for progression of 0.3 in cMET positive subgroup, defined as H-score of >= 150. References: 36977289

New Afatinib in Non-small cell lung cancer with EGFR H773L and V774M: R2

References: 31007929

Saturday, 25 March 2023 (Version: 20230325AU)

New Nirogacestat in Aggressive fibromatosis with APC Oncogenic mutations: 2

Not TGA approved. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria. References: 36884323

New Nirogacestat in Aggressive fibromatosis with CTNNB1 Oncogenic mutations: 2

Not TGA approved. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria. References: 36884323

Monday, 20 March 2023 (Version: 20230320AU)

New Trastuzumab Deruxtecan in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 3

Phase 2. DESTINY-Gastric01. NCT03329690. Confirmed ORR 26% (5/19, cohort 1, ISH-negative, IHC 2+) and 10%(2/21, cohort 2, IHC 1+). 13 (68%, cohort 1) and 12 (60%, cohort 2) experienced reduced tumor size. Median OS was 7.8 months (Cohort 1) and 8.5 months (Cohort 2). Median PFS 4.4 (Cohort 1) and 2.8 months (Cohort 2). References: 36379002

New Olaparib in Chondrosarcoma, Epithelioid hemangioendothelioma with IDH1 R132C, R132: 4

OLAPCO. Clinical benefit observed in 3 of 5 chondrosarcomas (1 PR and 2 SD). One prolonged SD in pulmonary epithelioid hemangioendothelioma. References: 34994649

New Olaparib in Chondrosarcoma, Epithelioid hemangioendothelioma with IDH2 R172K, R172: 4

OLAPCO. Clinical benefit observed in 3 of 5 chondrosarcomas (1 PR and 2 SD). One prolonged SD in pulmonary epithelioid hemangioendothelioma. References: 34994649

New Erlotinib in Head and neck squamous cell carcinoma with MAPK1 D321N: 4

Cell line study showing HNSCC cell line harbouring MAPK1 D321N mutation is sensitive to erlotinib in vivo. References: 32351709

New Erlotinib in Head and neck squamous cell carcinoma with MAPK1 E322K: 4

Case report. The HNSCC cells with MAPK1 E322K mutation causes constitutive activation of ERK2 and is associated erlotinib sensitivity in cell line models. References: 26181029

New Niraparib in Cholangiocarcinoma, Uveal melanoma, Mesothelioma, Clear cell renal cell carcinoma with BAP1 Oncogenic mutations; Loss-of-function mutations; Deletion: R2

NCT03207347. Phase 2. Cohort A. ORR 6% (1/18) failed to meet the primary endpoint and stopped at the first stage of Simon’s design. References: 10.1200/JCO.2022.40.16_suppl.3122

New Olaparib in Cholangiocarcinoma with IDH1 R132C, R132: R2

OLAPCO. No responses were seen in Cholangiocarcinoma harbouring IDH1/2 mutations treated with Olaparib. References: 34994649

New Olaparib in Cholangiocarcinoma with IDH2 R172K, R172: R2

OLAPCO. No responses were seen in Cholangiocarcinoma harbouring IDH1/2 mutations treated with Olaparib. References: 34994649

Wednesday, 8 March 2023 (Version: 20230308AU)

New Olaparib in Uterine leiomyosarcoma with BRCA2+PTEN BRCA2:deletion and PTEN:deletion: 4

Case report. References: 33970096

New Pembrolizumab in Non-small cell lung cancer with EGFR+CD274 CD274:Protein expression and EGFR:Oncogenic mutations: R2

NCT02879994. Phase 2. The ORR was <9% in in EGFR-Mutant, TKI naive patients treated with pembrolizumab. including PD-L1 expression ≥50%. References: 29874546

Changed Pembrolizumab + Trastuzumab + Cisplatin + Fluorouracil, Pembrolizumab + Trastuzumab + Capecitabine + Oxaliplatin in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 5/5/2021. Phase 3: KEYNOTE-811 (NCT03615326). First interim analysis. ORR 74% for pembro + SOC vs 52% for SOC alone. DOR 10.6 vs 9.5mo.Phase 3: KEYNOTE-811 (NCT03615326). First interim analysis. ORR 74% for pembro + SOC vs 52% for SOC alone. DOR 10.6 vs 9.5mo. PFS and OS are not yet mature.. References changed: 34912120, 10.1200/JCO.2021.39.15_suppl.4013.

Changed Tazemetostat in Ovarian small cell carcinoma with SMARCA2 Loss-of-function mutations: 4

References changed: 2829293524563539.

Changed Tazemetostat in Ovarian small cell carcinoma with SMARCA4 Loss of protein expression: 4

References changed: 2829293526356327.

Wednesday, 22 February 2023 (Version: 20230222AU)

New Ulixertinib in Low-grade gliomas with BRAF V600E, KIAA1549-BRAF fusion, Fusion: 4

References: 35882450

New E7090, Erdafitinib, Futibatinib in Cholangiocarcinoma with FGFR2 N549K: 4

References: 34272467

New E7090, Futibatinib in Cholangiocarcinoma with FGFR2 N549K: 4

References: 34272467

New AZD4547, Infigratinib, E7090, Erdafitinib, Futibatinib, Pemigatinib in Cholangiocarcinoma with FGFR2 N549S, N549H: 4

References: 34272467

New Ponatinib, Dovitinib in Cholangiocarcinoma with FGFR3 N540K, V555M, L608V: 4

References: 28034880

New Cisplatin, Olaparib in Endometrial cancer, Uterine serous carcinoma with Homologous Recombination Deficiency Score High: 4

Cell line studies suggest that models with high HRD score have higher sensitive to cisplatin and olaparib. References: 33563487

New AZD4547, Infigratinib, Erdafitinib, Pemigatinib in Cholangiocarcinoma with FGFR2 N549K: R2

References: 34272467

New AZD4547, Infigratinib, Pemigatinib in Cholangiocarcinoma with FGFR2 N549K: R2

References: 34272467

New Dovitinib in Cholangiocarcinoma with FGFR2 N549S, N549H: R2

References: 34272467

New Infigratinib in Cholangiocarcinoma with FGFR2 V564F, N549H, N549K, E565A, L617V, K641R, K659M: R2

References: 28034880

New Infigratinib, AZD4547, Debio1347 in Cholangiocarcinoma with FGFR3 N540K, V555M, L608V: R2

References: 28034880

Monday, 20 February 2023 (Version: 20230220AU)

New PD173074 in Colorectal cancer with FGFR1 Overexpression: 4

Cell line study. References: 31096734

New PD173074 in Colorectal cancer with FGFR1 Amplification: R2

Cell line study. References: 31096734

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification

Tier changed: 1B2.

Tuesday, 14 February 2023 (Version: 20230214AU)

Changed Sacituzumab Govitecan in Triple-negative breast cancer with ESR1+ERBB2 NOT ESR1:protein expression and NOT ERBB2:amplified

Tier changed: 12. Comments changed: TGA approved; Not PBS reimbursed. FDA approved. Anti Trop-2 ADC. Phase 1/2: ORR 33%. Median DOR 7.7 months. CBR 45%. Median PFS: 5.5 months. Phase 3 ASCENT trial: OS: 12.1 vs 6.7 months (chemotherapy).Not TGA approved; FDA approved. Anti Trop-2 ADC. Phase 1/2: ORR 33%. Median DOR 7.7 months. CBR 45%. Median PFS: 5.5 months. Phase 3 ASCENT trial: OS: 12.1 vs 6.7 months (chemotherapy)..

Changed Trastuzumab + Tucatinib in Colorectal adenocarcinoma with ERBB2 Amplification, Overexpression

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 19/01/2023. Phase 2. Single-arm study. MOUNTAINEER. NCT03043313. N=84. In metastatic CRC after two-lines of systemic treatment, the tucatinib and trastuzumab combination resulted in ORR of 38% (Cohorts A + B). Median DOR was 12.4 months. Median PFS 8.2 months. Median OS was 24.1 months at follow-up of 20.7 months..

Changed Elacestrant in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

Comments changed: Not TGA approved. FDA approved 27/01/2023. Phase 3. EMERALD trial. In patients with ER-postive HER2-negative metastatic breast cancer treated with prior CDK4/6 inhibitor and up to 2 lines of endocrine therapy, SERD Elacestrant significantly improved PFS over standard-of-care endocrine therapy (6 month PFS rate: 34% vs 20%, 12 month PFS: 22 vs 9%).Not TGA approved. Phase 3. EMERALD trial. In patients with ER-postive HER2-negative metastatic breast cancer treated with prior CDK4/6 inhibitor and up to 2 lines of endocrine therapy, SERD Elacestrant significantly improved PFS over standard-of-care endocrine therapy (6 month PFS rate: 34% vs 20%, 12 month PFS: 22 vs 9%)..

Changed Sacituzumab govitecan in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

References changed: 36027558, JCO.2022.40.17_suppl.LBA1001.

Changed Mirvetuximab Soravtansine in Ovarian cancer with FOLR1 Expression: 2

Comments changed: Not TGA approved. FDA approved 14/11/2022. SORAYA. NCT04296890.Not TGA approved. FDA approved. SORAYA. NCT04296890..

Changed Dostarlimab in Endometrial cancer with Microsatellite Instability High: 2

Comments changed: GARNET trial: dMMR as assessed by IHC or MSI-H by PCR or NGS. ORR 43% with 13% CR. Duration of response at 6 months: 96%. FDA approved 09/02/2023.GARNET trial: dMMR as assessed by IHC or MSI-H by PCR or NGS. ORR 43% with 13% CR. Duration of response at 6 months: 96%. FDA approved..

Wednesday, 25 January 2023 (Version: 20230125AU)

New Sunitinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 13 mutation, Exon 11 mutation and Exon 14 mutation: 3

Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. ORR was 25% in patients with acquired Exon 13/14 mutations following prior imatinib exposure. References: 10.1200/JCO.2023.41.36_suppl.397784

New Sunitinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation: 3

Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. ORR 44% (12/27) was observed in patients with acquired Exon 13/14 mutations prior imatinib exposure. Median PFS 14.2 months. References: 10.1200/JCO.2023.41.36_suppl.397784

New Olaparib + Ceralasertib in Ovarian cancer with BRCA1 Oncogenic mutations: 4

NCT03462342. In the CAPRI trial (recurrent, platinum-resistant epithelial ovarian cancer), CA125 and tumour size reductions were seen in 3 patients with BRCA1 mutations (1 germline and 2 somatic), although no radiological response was observed. No objective responses occurred in the overall cohort. References: 34620496

New Olaparib + Ceralasertib in Ovarian cancer with BRCA1 Oncogenic mutations, Reversion mutations: 4

Preclinical study. Durable responses were observed with combined inhibition of PARP and ATR in platinum-resistant and acquired PARPi-resistant PDXs models of BRCA-associated high-grade ovarian serous carcinoma. References: 32709856

New Olaparib + Ceralasertib in Ovarian cancer with BRCA2 Oncogenic mutations, Reversion mutations: 4

Preclinical study. Durable responses were observed with combined inhibition of PARP and ATR in platinum-resistant and acquired PARPi-resistant PDXs models of BRCA-associated high-grade ovarian serous carcinoma. References: 32709856

New Olaparib + Ceralasertib in Ovarian cancer with CCNE1 Amplification: 4

Preclinical study. Durable responses were observed with combined inhibition of PARP and ATR in platinum-resistant and acquired PARPi-resistant PDXs models of BRCA-associated high-grade ovarian serous carcinoma. References: 32709856

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-small cell lung cancer with DNMT3A Loss-of-function mutations: 4

References: 10.1200/JCO.2021.39.15_suppl.9113

New Sunitinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation: R2

Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. No response in 25 patients was observed in patients with acquired Exon 13/14 mutations prior imatinib exposure. Median PFS 1.5 months. References: 10.1200/JCO.2023.41.36_suppl.397784

Removed in with FGFR2 alterations : Tier 2

Monday, 23 January 2023 (Version: 20230123AU)

New Infigratinib in Cholangiocarcinoma with FGFR2 Fusion and E566G: 4

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New Futibatinib in Cholangiocarcinoma with FGFR2 Fusion and N550D, Fusion and N550K, Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642I, Fusion and K642R, Fusion and K660M: 4

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New Erdafitinib in Cholangiocarcinoma with FGFR2 Fusion and N550D, Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642R: 4

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New Pemigatinib in Cholangiocarcinoma with FGFR2 Fusion and V563L, Fusion and E566A, Fusion and E566G, Fusion and K642R: 4

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New Infigratinib in Cholangiocarcinoma with FGFR2 N550D, N550K, V563I, V565I, V565L, E566A, E566G, K642I, L642R, K660M: R2

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New Pemigatinib in Cholangiocarcinoma with FGFR2 N550D, N550K, V565I, V565L, K642I, K660M: R2

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New Erdafitinib in Cholangiocarcinoma with FGFR2 N550K, V565L, K642I, K660M: R2

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New Futibatinib in Cholangiocarcinoma with FGFR2 V565L: R2

FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells. References: 36652354

New in with FGFR2 : 2

References:

Changed Futibatinib in Cholangiocarcinoma with FGFR2 Fusions

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 30/09/2022. NCT02052778. FOENIX-CCA2. Single-arm Phase 2 study. Intrahepatic cholangiocarcinoma. ORR 42% (43/103). DCR was 83%. median PFS 9.0 months. Median OS 21.7 months.NCT02052778. FOENIX-CCA2. Single-arm Phase 2 study. Intrahepatic cholangiocarcinoma. ORR 42% (43/103). DCR 83%. mPFS 8.9 months. Median OS 20.0 months.. References changed: 36652354, 10.1200/JCO.2020.38.15_suppl.108, 10.1200/JCO.2022.40.16_suppl.4009.

Friday, 20 January 2023 (Version: 20230120AU)

New Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 2

Phase 3. SPOTLIGHT. NCT03504397. Addition of Zolbetuximab significantly prolonged both PFS and OS in previously untreated patients with Claudin 18.2 positive and HER2 negative gastric and gastroesophageal cancers (median PFS 10.6 vs 8.7 months, median OS 18.2 vs 15.5 months). CLDN18 positive was defined as moderate-to-strong IHC staining in >= 75% of tumour cells. References: 10.1200/JCO.2023.41.3_suppl.LBA292

New Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3

Phase 2. ILUSTRO. N=19. In Claudin 18.2-positive, previously untreated locally advanced or metastatic GEJ cancers (Cohort 2), ORR was 63% (12/19), and median PFS was 13.7 months. References: 10.1200/JCO.2021.39.15_suppl.e16063

New IMU-131 in Solid tumours with ERBB2 Overexpression, Protein expression, Amplification: 3

Phase Ib Trial IMU.ACS.001. NCT02795988. Objective response seen in 5 of 14 patients. References: 33879458

Wednesday, 18 January 2023 (Version: 20230118AU)

New Imatinib in Gastrointestinal stromal tumour with PDGFRA P567P, I843del, D842del, R560del, V516D, I843_D846del, Exon 12 mutation, Exon 18 deletion: 4

Retrospective study. Responses (5/7) were seen in patients with Non-D842V exon 18 mutations and exon 12 mutations. References: 26130666

New Imatinib, Sunitinib in Gastrointestinal stromal tumour with PDGFRA W559_R560del: 4

Case report. References: 26396737

New Olaparib in Solid tumours with RAD51C Low protein expression; No protein expression: 4

In cell line models, RAD51C-deficient cells are sensitive to olaparib. References: 23512992

New Rucaparib, Niraparib in Ovarian cancer with RAD51C Promoter methylation: 4

References: 34321239

New Rucaparib, Niraparib in Ovarian cancer with RAD51C Loss of promoter methylation: R2

References: 34321239

New Encorafenib + Capamatinib in Colorectal adenocarcinoma with BRAF+MET BRAF:V600E AND MET:amplification: 4

Case report. References: 34994629

New Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+MET BRAF:V600E AND MET:amplification: R2

Case report. References: 34994629

New Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+KRAS BRAF:V600E AND KRAS:G12D, BRAF:V600E AND KRAS:Oncogenic mutations: R2

Case report. References: 34994629

Thursday, 12 January 2023 (Version: 20230112AU)

Wednesday, 11 January 2023 (Version: 20230111AU)

New Afatinib, Neratinib, Poziotinib in Acute myeloid leukaemia with ERBB2 P489L, L1157R: 4

References: 32366937

New Afatinib, Neratinib, Poziotinib in Acute lymphoblastic leukaemia with ERBB2 R188C: 4

References: 32366937

New Pembrolizumab in SMARCA4-deficient thoracic sarcoma with SMARCA4 Oncogenic mutations: 4

Case report. References: 31617320

Friday, 23 December 2022 (Version: 20221223AU)

New Sotorasib in Pancreatic adenocarcinoma with KRAS G12C: 3

Phase 2. NCT03600883. CodeBreaK 100. N=38. Median prior treatment 2 lines. Objective response 21% (8/38). Median PFS 4.0 months. Median OS 6.9 months. References: 36546651

New Datopotamab Deruxtecan in Solid tumours with TACSTD2 Protein expression, Overexpression: 4

References: 34413126

Wednesday, 21 December 2022 (Version: 20221221AU)

New Crizotinib, Foretinib in Glioblastoma with MET PTPRZ-MET fusion, TFG-MET fusion: 4

References: 27748748

Changed Adavosertib in Ovarian cancer, Solid tumours with CCNE1 Amplification: 3

References changed: 36469840.

Tuesday, 20 December 2022 (Version: 20221220AU)

New RP-6306 in Solid tumours with CCNE1 Amplification, Overexpression: 4

Inhibition of the PKMYT1 kinase is synthetic lethal in solid tumour vivo models harbouring amplification of CCNE1 gene. References: 35444283

Wednesday, 14 December 2022 (Version: 20221214AU)

New Aumolertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 2

Not TGA approved. EMA approved. AENEAS. Phase 3. NCT03849768. Median DOR of Aumolertinib was 18.1 months vs Gefitinib 8.3 months. References: 35580297

Changed Adagrasib in Non-small cell lung cancer with KRAS G12C: 2

Comments changed: Not TGA approved. FDA approved 12/12/2022. NCT03785249. In patients with previously treated metastatic non-small cell lung cancer, treatment with adagrasib resulted in ORR of 48/112 (43%), median PFS of 6.5 months and median OS of 12.6 months..

Thursday, 8 December 2022 (Version: 20221208AU)

New Adavosertib in Ovarian cancer, Solid tumours with CCNE1 Amplification: 3

Phase 2. NCT03253679. NCI 10136. Adavosertib monotherapy. N=33. ORR 27%. Median PFS 4.1 months. Median OS as 9.9 months. In epithelial ovarian cancer, ORR was 36% and DCR at 6 months of 57%. CCNE1 amplification was determined by NGS platforms at the threshold of genomic copy number of > 7 copies. References:

Changed Fulvestrant + Palbociclib in Breast cancer with ESR1 Oncogenic mutations: 2

References changed: 36183733.

Wednesday, 7 December 2022 (Version: 20221207AU)

New Palbociclib in Breast cancer with ESR1 Fusion, ESR1-YAP1 fusion, ESR1-PCDH11X fusion: 4

References: 30089255

New MRTX1133 in Pancreatic adenocarcinoma with KRAS G12D: 4

References: 36472553

New Fulvestrant in Breast cancer with ESR1 ESR1-YAP1 fusion, ESR1-PCDH11X fusion, ESR1-SOX9 fusion, ESR1-ARNT2 fusion: R2

References: 34711608

New Tamoxifen, Letrozole, Fulvestrant in Breast cancer with ESR1 Fusion, ESR1-YAP1 fusion, ESR1-PCDH11X fusion: R2

References: 30089255

Changed Olutasidenib in Acute myeloid leukaemia with IDH1 R132

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 2022-12-01. Phase 2. NCT02719574. Interim anaylsis. ORR 57% (46/123). CR 30% (37/123). Median OS 10.5 months with duration of treatment 5.5 months..

Changed Letrozole + Palbociclib, Anastrozole + Palbociclib, Exemestane + Palbociclib in Breast cancer with ESR1 Oncogenic mutations: R2

References changed: 36183733.

Tuesday, 29 November 2022 (Version: 20221129AU)

New KIN-2787 in Solid tumours with BRAF Class II mutations, Class III mutations: 4

References: 10.1200/JCO.2021.39.15_suppl.3116, 10.1158/1538-7445.AM2022-2674

Changed Vemurafenib + Cobimetinib in Colorectal adenocarcinoma with BRAF V600: 3

Comments changed: TAPUR Phase 2 Basket trial. The ORR was 30%, and the DCR was 52%. Median duration of therapy was 8.1 weeks. Median PFS was 15.7 weeks.TAPUR Phase 2 Basket trial. ORR 29%.. References changed: 36409971, 10.1200/JCO.2020.38.4_suppl.122.

Monday, 28 November 2022 (Version: 20221128AU)

New Olaparib, Rucaparib, Talazoparib in Solid tumours with ARID2 Loss-of-function mutations, Loss of protein expression: 4

References: 33888468

New Olaparib, Rucaparib, Talazoparib in Solid tumours with PBRM1 Loss-of-function mutations, Loss of protein expression: 4

References: 33888468

Friday, 25 November 2022 (Version: 20221125AU)

New Trastuzumab deruxtecan in Gastroesophageal junction adenocarcinoma, Gastric Cancer with ERBB2 Protein expression, Protein expression NOT amplification: 3

DESTINY-Gastric 01. NCT03329690. Exploratory cohort. In IHC 2+ / ISH negative cohort, ORR was 26% (5/19), meeting the prespecified endpoint. DCR 90%. References: 36379002

New Trastuzumab deruxtecan in Gastroesophageal junction adenocarcinoma, Gastric Cancer with ERBB2 Low protein expression: R2

DESTINY-Gastric 01. NCT03329690. Exploratory cohort. In IHC 1+ cohort, ORR was 9.5% (2/21) and did not meet the prespecified endpoint. DCR 71%. References: 36379002

Wednesday, 23 November 2022 (Version: 20221123AU)

New Zanidatamab in Solid tumours with ERBB2 Amplification, Overexpression: 3

Phase 1. ORR 37% (31/83). CBR 51%. DCR 75%. References: 10.1016/S1470-2045(22)00621-0

Wednesday, 16 November 2022 (Version: 20221116AU)

New Mirvetuximab Soravtansine in Ovarian cancer with FOLR1 Expression: 2

Not TGA approved. FDA approved. SORAYA. NCT04296890. References: 33667670

New AMG-193 in Solid tumours with MTAP Deletion: 4

References: NCT05094336

Changed Larotrectinib in Solid tumours with NTRK2 : R1

Alterations changed: Q596E, Q596P, G623S, F633LQ596E, Q596P, F617L, F617C, F617I, G623S.

Changed Larotrectinib in Solid tumours with NTRK3 : R1

Alterations changed: G623R, G696A, F617L, F617L, F617C, F617I.

Monday, 14 November 2022 (Version: 20221114AU)

New Ipatasertib in Solid tumours with AKT E17K: 3

NCT02465060. NCI-MATCH ECOG-ACRIN Trial (EAY131) Sub-protocol Z1K. ORR 22%. DOR 9.9 months. References: 10.1016/S0959-8049(22)00824-3

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 Fusions, FGFR2-ACLY fusion, FGFR2-AFF4 fusion, FGFR2-AHCYL1 fusion, FGFR2-ARHGAP22 fusion, FGFR2-ARHGAP24 fusion, FGFR2-ATAD2 fusion, FGFR2-ATF2 fusion, FGFR2-BICC1 fusion, FGFR2-BICD1 fusion, FGFR2-CCDC158 fusion, FGFR2-CCDC170 fusion, FGFR2-CCDC6 fusion, FGFR2-CEP128 fusion, FGFR2-COL16A1 fusion, FGFR2-CTNNA3 fusion, FGFR2-DBP fusion, FGFR2-DNAJC12 fusion, FGFR2-EEA1 fusion, FGFR2-EIF4ENIF1 fusion, FGFR2-FILIP1 fusion, FGFR2-GAB2 fusion, FGFR2-GOPC fusion, FGFR2-INSC fusion, FGFR2-KCTD1 fusion, FGFR2-KIAA1217 fusion, FGFR2-KIAA1598 fusion, FGFR2-LAMC1 fusion, FGFR2-MACF1 fusion, FGFR2-MATR3 fusion, FGFR2-MCU fusion, FGFR2-NEDD4L fusion, FGFR2-NOL4 fusion, FGFR2-NRAP fusion, FGFR2-NRBF2 fusion, FGFR2-PAH fusion, FGFR2-PAWR fusion, FGFR2-POC1B fusion, FGFR2-PXN fusion, FGFR2-RABGAP1L fusion, FGFR2-RASSF4 fusion, FGFR2-RPAP3 fusion, FGFR2-SFI1 fusion, FGFR2-SHROOM3 fusion, FGFR2-SLMAP fusion, FGFR2-SOGA1 fusion, FGFR2-SPICE1 fusion, FGFR2-STRN4 fusion, FGFR2-TACC1 fusion, FGFR2-TFEC fusion, FGFR2-TRIM8 fusion, FGFR2-TTC28 fusion, FGFR2-TXLNB fusion, FGFR2-USH2A fusion, FGFR2-VCL fusion, FGFR2-WAC fusion, FGFR2-WDHD1 fusion, FGFR2-ZMYM4 fusion

Tier changed: 1B2. Comments changed: TGA approved; Not PBS reimbused; FIGHT-202Not TGA approved; FDA approved; FIGHT-202.

Friday, 4 November 2022 (Version: 20221104AU)

New Trastuzumab + Pertuzumab in Colorectal adenocarcinoma with ERBB2 Amplification: 3

Phase 2. NCT02693535. TAPUR. N=28 in Cohort 1. ORR was 25%. DCR 54%. DOR 4.8 months. References: 36315917

New Olaparib in Renal cell carcinoma with FLCN Loss-of-function mutations: 4

Preclinical study. FLCN protein deficiency is associated with olaparib sensitivivty in cell line and xenograft models. References: 33069804

New Sirolimus in Renal cell carcinoma with FLCN Loss-of-function mutations: 4

Preclinical study. mTOR inhibitor, sirolimus, showed suppression of the tumour growth in Flcn-deficient allograft xenograft models. References: 26418749

New Trastuzumab + Pertuzumab in Colorectal adenocarcinoma with ERBB2 G309A, G309E, S310F, D769H, D769Y, L755S, V777L, V842I, E321G, R896C, P780ins, L755_T759del, R678Q: R2

Phase 2. NCT02693535. TAPUR. N=28 in Cohort 2. ORR was 0%. DCR 10%. References: 36315917

New Trastuzumab + Pertuzumab in Colorectal adenocarcinoma with ERBB3 Oncogenic mutations: R2

Phase 2. NCT02693535. TAPUR. N=28 in Cohort 2. ORR was 0%. DCR 10%. References: 36315917

Tuesday, 1 November 2022 (Version: 20221101AU)

New Neratinib in Breast cancer with ERBB2 Amplification and D769Y: 4

Xenograft model. Neratinib was shown to reduce tumour volume in a breast cancer PDX model that harbour both ERBB2 amplification and HER2 D769Y mutation. References: 30301790

New Neratinib in Breast cancer with ERBB2 Amplification and L755S, Amplification and A775_G776insTVMA, Amplification and V777L, Amplification and L313I, Amplification and R456C, Amplification and D769Y: 4

In retrospective series, Neratinib was seen to confer clinical benefit in breast cancer that harbour both ERBB2 amplification and oncogenic mutations. References: 30301790

New Bemarituzumab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with FGFR2 Overexpression: 4

Randomised phase 2. NCT03694522. N=155. The primary endpoint of median PFS showed a trend longer in the Bemarituzumab group versus placebo (9.5 vs 7.4 months) but did not reach the pre-specified threshold. FGFR overexpresspression was defined as IHC 2+/3+ in >0% of cells. Note in the exploratory analysis of FGFR2b overexpressed group in >= 10%, HR for PFS was 0.44; the OS of overall population was 0.58. References: 36244398

New Ivosidenib, Olutasidenib, Vorasidenib in Cholangiocarcinoma with IDH1 R132, R132C, R132L, R132G: 4

Multicentre retrospective series. Median PFS was 4.6 months with DCR 29% in 15 (23%) patients treated with IDH inhibitors. References: 35005992

New Enasidenib in Cholangiocarcinoma with IDH2 R172, R172M, R172K, R172G, R172W, R172T: 4

Multicentre retrospective series. Median PFS was 4.6 months with DCR 29% in 15 (23%) patients treated with IDH inhibitors. References: 35005992

New Lapatinib, Trastuzumab in Breast cancer with ERBB2 Amplification and D769Y: R2

Xenograft model. Trastuzumab and lapatinib did not show activity in a breast cancer PDX model that harbour both ERBB2 amplification and HER2 D769Y mutation. References: 30301790

Thursday, 20 October 2022 (Version: 20221020AU)

New Rogaratinib in Urothelial carcinoma with FGFR1 High mRNA expression: 3

NCT03410693. Randomised Phase 2. FORT-1. FGFR1/3 mRNA positive population. N=87 in the Rogaratinib group. ORR was 21% (18/87), and median OS was 8.3 months. However, neither ORR or OS was superior to chemotherapy group. References: 36240478

New Rogaratinib in Urothelial carcinoma with FGFR3 High mRNA expression: 3

NCT03410693. Randomised Phase 2. FORT-1. FGFR1/3 mRNA positive population. N=87 in the Rogaratinib group. ORR was 21% (18/87), and median OS was 8.3 months. However, neither ORR or OS was superior to chemotherapy group. References: 36240478

New Rogaratinib in Urothelial carcinoma with FGFR3 Overexpression; High mRNA expression: 4

Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation). References: 31405822

New DYP688 in Uveal melanoma with GNA11 Oncogenic mutations: 4

References: NCT05415072

New DYP688 in Uveal melanoma with GNAQ Oncogenic mutations: 4

References: NCT05415072

Changed Rogaratinib in Urothelial carcinoma with FGFR3 : 4

Alterations changed: High mRNA expression and Oncogenic mutation; High mRNA expression and G370C; High mRNA expression and R248C; High mRNA expression and S249C; High mRNA expression and Y373C; High mRNA expression and FGFR3-TACC3 fusionOverexpression. Comments changed: NCT03410693. Randomised Phase 2. FORT-1. FGFR1/3 mRNA positive population. Post hoc exploratory analysis showed that in FGFR3 DNA alterations (oncogenic mutations and fusions, n=21) showed an ORR of 52% (11/21), compared to chemotherapy 27% (4/15).Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation). References changed: 3624047831405822.

Changed Therapy in Solid tumours, Uveal melanoma with GNA11 Oncogenic mutations: 4

Therapy changed: IDE196, Crizotinib + IDE196, Binimetinib + IDE196.

Changed Therapy in Solid tumours, Uveal melanoma with GNAQ Oncogenic mutations: 4

Therapy changed: IDE196, Crizotinib + IDE196, Binimetinib + IDE196.

Tuesday, 18 October 2022 (Version: 20221018AU)

New Crizotinib in Solid tumours with ALK Fusion: 3

NCI-MATCH (EAY131) Subprotocol F. N=4 with ORR of 50%. References: 35233056

New TYRA-300 in Solid tumours with FGFR3 Fusions, V555M, V555L: 4

References: 10.1016/j.annonc.2022.07.591

New Palbociclib in Non-small cell lung cancer with CDKN2A Deletion, Oncogenic mutations: R2

N=29. ORR 3% (1 PR). DCR 31%. Median PFS 8 weeks. References: 35050752

New Palbociclib in Pancreatic adenocarcinoma, Biliary tract cancer with CDKN2A Deletion, Oncogenic mutations: R2

TAPUR. N=22. ORR 0%. References: 35100714

New Sunitinib in Colorectal adenocarcinoma with FLT3 Amplification: R2

NCT02693535. TAPUR. ORR 0%. References: 33068284

New Cetuximab in Breast cancer, Non-small cell lung cancer, Ovarian cancer with KRAS+NRAS+BRAF NOT KRAS:Oncogenic mutation and NOT NRAS:Oncogenic mutation and NOT BRAF:Oncogenic mutation: R2

NCT02693535. TAPUR. N=49 including breast, NSCLC, and ovarian cancers. ORR 0%. References: 33090333

New Taselisib in Solid tumours except Breast cancer, Gastric cancer, Lung squamous cell carcinoma with PIK3CA Oncogenic mutations: R2

NCT02465060. NCI-MATCH (EAY131) Subprotocol I. N=61. ORR 0%. PFS rate at 6 months was 20%. References: 35138919

Wednesday, 12 October 2022 (Version: 20221012AU)

New RLY-4008 in Cholangiocarcinoma with FGFR2 Fusion: 3

Phase 1. ReFOCUS. ORR was 63% (24/38); 88% (15/17) at RP2D with DCR 100%. References: 10.1016/j.annonc.2022.08.006

Tuesday, 11 October 2022 (Version: 20221011AU)

New Selpercatinib, Pralsetinib in Non-small cell lung cancer with KRAS Amplification: R2

Retrospective study. The study identified acquisition of RET kinase solvent front mutations (G810), as well as genomic amplification of MET and KRAS as potential bypass mechanisms. References: 33007380

New Selpercatinib, Pralsetinib in Non-small cell lung cancer with MET Amplification: R2

Retrospective study. The study identified acquisition of RET kinase solvent front mutations (G810), as well as genomic amplification of MET and KRAS as potential bypass mechanisms. References: 33007380

New Selpercatinib, Pralsetinib in Non-small cell lung cancer with RET G810S, G810R: R2

Retrospective study. The study identified acquisition of RET kinase solvent front mutations (G810), as well as genomic amplification of MET and KRAS as potential bypass mechanisms. References: 33007380

Monday, 10 October 2022 (Version: 20221010AU)

Changed Selumetinib with NF1 Oncogenic mutations (germline): 2

Cancer type(s) changed: Low-grade gliomas, Paediatric low grade gliomas, Type 1 neurofibromatosisGlioma, Paediatric low grade gliomas, Type 1 neurofibromatosis

Changed Trabectedin in Ovarian cancer with BRCA1 Oncogenic mutations: R2

Comments changed: Phase 3. NCT02993705. MITO-203. In heavily pretreated platinum resistant ovarian cancer that harbours a BRCA mutation or has BRCA phenotypes, Trabectedin does not improve PFS (4.9 vs 4.4 months), OS, or objective response rate over standard chemotherapy (18% vs 22%). Exploratory analysis showed that OS was similar to non-platinum arm (median 15.8 v 16.0 months), and inferior to carboplatin arm (median OS 22.0 months).Phase 3. NCT02993705. MITO-203. In heavily pretreated platinum resistant ovarina cancer that harbour a BRCA mutation or has BRCA phenotypes, Trabectedin does not improve PFS (4.9 vs 4.4 months), OS, or objective response rate over standard chemotherapy (18% vs 22%). Exploratory analysis showed that OS was similar to non-platinum arm (median 15.8 v 16.0 months), inferior to carboplatin arm (median 22.0 months)..

Saturday, 8 October 2022 (Version: 20221008AU)

New Fulvestrant + Palbociclib in Breast cancer with ESR1 Oncogenic mutations: 2

Phase 3. PADA-1. NCT03079011. Median PFS from randomisation was significantly longer in patients switching to Fulvestrant + Palbociclib from Aromatase Inhibitor + Palbociclib (11.9 vs 5.7 months) in patients after detection of rising ESR1 resistance mutation in the circulating tumour DNA assay. References:

New Letrozole + Palbociclib, Anastrozole + Palbociclib, Exemestane + Palbociclib in Breast cancer with ESR1 Oncogenic mutations: R2

Phase 3. PADA-1. NCT03079011. Median PFS from randomisation was significantly longer in patients switching to Fulvestrant + Palbociclib from Aromatase Inhibitor + Palbociclib (11.9 vs 5.7 months) in patients after detection of rising ESR1 resistance mutation in the circulating tumour DNA assay. References:

Friday, 7 October 2022 (Version: 20221007AU)

New Derazantinib in Cholangiocarcinoma with FGFR2 Fusion: 3

Phase 2. FIDES-01. NCT03230318. In patients with intrahepatic cholangiocarcinoma harbouring a FGFR2 fusion (N=143), ORR was 21%, DCR was 76%. Median OS was 17.2 months and PFS was 8.0 months. References: 10.1016/j.annonc.2022.07.087

Thursday, 6 October 2022 (Version: 20221006AU)

Changed Everolimus in Pancreatic adenocarcinoma with STK11 Oncogenic mutations: 4

References changed: 2118937827615706.

Changed Everolimus in Pituitary adenoma with STK11 Oncogenic mutations: 4

References changed: 2761570621189378.

Wednesday, 5 October 2022 (Version: 20221005AU)

Changed Nivolumab + FOLFOX, Nivolumab + CAPOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CD274 Protein expression

Tier changed: 12. Comments changed: TGA approved. FDA approved. Checkmate-649: Phase 3. First-line, HER2-negative gastric/GOJ carcinoma. Nivolumab plus chemotherapy improved PFS (7.7 vs 6.1 months) and OS (14.4 vs 11.1) over chemotherapy alone in PD-L1 CPS ≥ 5, as well as in CPS>= 1 (PFS: 7.5 vs 6.9 months) and (OS: 14.0 vs 11.3 months). No PFS or OS difference in PD-L1 CPS <5 or CPS <1 subgroups.Not TGA approved. CheckMate 649: Phase III, First-line, HER2-negative gastric/GOJ carcinoma. Nivolumab plus chemotherapy improved PFS (7.7 vs 6.0 months) over chemotherapy alone in PD-L1 positive population. PD-L1 positivity was defined as CPS ≥ 5%..

Tuesday, 4 October 2022 (Version: 20221004AU)

New Futibatinib in Cholangiocarcinoma with FGFR2 C383R, W290C: 3

NCT02052778. TAS-120-101. Phase 1 dose expansion. Responders seen in cholangiocarcinoma (1 patient each) harbouring C383R and W290C. References: 34551969

New Avelumab + Axitinib in Thymic carcinoma, Thymoma with PBRM1 Oncogenic mutations: 4

Phase 2. PECATI trial. NCT04710628. Risk ratio of response to the combination in patients with PBRM1 mutation was 4.0. References: 36096156

New Nivolumab in Renal cell carcinoma with PBRM1 Truncating mutations: 4

Exploratory analysis of CheckMate025 data. Odds ratio of response and clinical beneift to Nivolumab were higher (2.34 and 2.14 respectively) in patients with PBRM1 mutations. RCC with PBRM1 mutation was associated with increased PFS (5.6 v 2.9 months) and OS (27.9 vs 20.9 months) respectively. References: 31486842

Changed Pemigatinib in Myelodysplastic/myeloproliferative diseases, Myeloproliferative diseases, Acute lymphoblastic leukaemia, Acute myeloid leukaemia with FGFR1 Rearrangement, Fusion: 2

References changed: 10.1182/blood-2021-148103.

Changed Futibatinib in Cholangiocarcinoma with FGFR2

Alterations changed: Fusion, FGFR2-POC1B fusion, FGFR2 rearrangement, C383R, W290C,. Tier changed: 23. Comments changed: Not TGA approved. FDA approved 30/09/2022. NCT02052778. TAS-120-101. Phase 1 dose expansion. Overall, the ORR of the study was 14% (25% in cholangiocarcinoma). In the 20 mg daily dose cohort (N=64), ORR was 16% and DCR was 72%. DOR 5.3 months. In the 16 mg cohort (N=16), ORR was 42% (8/19). Responders included patients previously treated with other FGFR inhibitors.NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14% (25% in cholangiocarcinoma). In the 20 mg daily dose cohort (N=64), ORR was 16% and DCR was 72%. DOR 5.3 months. In the 16 mg cohort (N=16), ORR was 42% (8/19). Responders included patients previously treated with other FGFR inhibitors..

Changed Selpercatinib in Solid tumours with RET Fusion: 2

Comments changed: Not TGA approved. FDA Approved 21/09/2022. LIBRETTO-001. NCT03157128. ORR was 44% (18/41 efficacy-evaluable population) with median DOR was 24.5 months.Not TGA approved. FDA Approved 21/09/2022. LIBRETTO-001. NCT03157128. ORR 44% (18/41) with median DOR was 24.5 months.. References changed: 36108661, 10.1200/JCO.2022.40.16_suppl.3094.

Wednesday, 28 September 2022 (Version: 20220928AU)

New Debio1347 in Cholangiocarcinoma with FGFR2 Extracellular domain deletion, H167_N173del, L618F: 4

Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Debio1347 experienced treatment response. References: 33926920

New Futibatinib in Cholangiocarcinoma with FGFR2 L618F: 4

References: 33926920

New Palbociclib in Gastrointestinal stromal tumour with CDKN2A Deletion: R2

Phase 2. NCT01907607. ORR 0%. References: 30979737

New Debio1347 in Cholangiocarcinoma with FGFR2 L618F: R2

References: 33926920

Friday, 23 September 2022 (Version: 20220923AU)

Changed Selpercatinib in Solid tumours with RET Fusion

Tier changed: 23. Comments changed: Not TGA approved. FDA Approved 21/09/2022. LIBRETTO-001. NCT03157128. ORR 44% (18/41) with median DOR was 24.5 months..

Changed Selpercatinib in Non-small cell lung cancer with RET Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion: 2

Comments changed: Not TGA approved. FDA Approved 21/09/2022. LIBRETTO-001: First-line treatment. ORR 85%.Not TGA approved. LIBRETTO-001: First-line treatment. ORR 85%.

Changed Selpercatinib in Thyroid cancer with RET Fusions, CCDC6-RET fusion, NCOA4-RET fusion, CCDC186-RET fusion, ERC1-RET fusion, KTN1-RET fusion, RUFY3-RET fusion: 2

Comments changed: Not TGA approved. FDA Approved. LIBRETTO-001Not TGA approved. LIBRETTO-001.

Changed Selpercatinib in Medullary thyroid cancer with RET Oncogenic mutations and NOT Amplification, M918T, V804M, V804L, C609, C611, C618, C620, C630, C634, D631_L633delinsE, E632_L633del, A883F, D631_L633delinsV, L790F, D898_E901del, D903_S904delinsEP, K666N, T636_V637insCRT, D378_G385delinsE: 2

Comments changed: Not TGA approved. FDA Approved. LIBRETTO-001. ORR 69%Not TGA approved. LIBRETTO-001. ORR 69%.

Monday, 19 September 2022 (Version: 20220919AU)

New Alectinib in Solid tumours with ALK EML4-ALK fusion, F1174L, R1275Q, L1196M, C1156Y: 4

References: 21575866

New Crizotinib in Solid tumours with ALK L1196M, C1156Y: R2

References: 21575866

Wednesday, 14 September 2022 (Version: 20220914AU)

New CYH33 in Solid tumours with PIK3CA Oncogenic mutations, E545A, E545K, E542K: 4

References: 10.1016/j.annonc.2021.01.048

New Buparlisib in Metaplastic breast carcinoma with PIK3CA Oncogenic mutations, H1047R: 4

Case report from BELLE-4. Confirmed partial response for 17 months in total. References: 30577988

Changed Cabozantinib with MET Y1248H (Y1230H), D1246N (D1228N), K1262R (K1244R): 4

Cancer type(s) changed: Solid tumoursGastrointestinal stromal tumour

Wednesday, 7 September 2022 (Version: 20220907AU)

New Trametinib in Melanoma with BRAF G469R, A598_T599insV, AGAP3-BRAF fusion, L597Q, T470R: 3

Phase 2. NCT02296112. Trametinib in non-V600 BRAF fusions. ORR was 33% (3/9). Median PFS 7.3 months. References: 33861486

New Afatinib in Non-small cell lung cancer with ERBB2 A775_G776insYVMA, M774dup: 3

Global named used program. Heavily pretreated NSCLC with ERBB2 mutation. N=28. ORR of 19% (3/16) with DCR of 69% (11/16). References: 30096481

New GDC0623, PD0325901, Trametinib, Selumetinib, LY3009120 in Melanoma with BRAF Fusions, FKBP15-BRAF fusion, TARDBP-BRAF fusion, AGK-BRAF fusion, SKAP2-BRAF fusion, CUL1-BRAF fusion, KIAA1549-BRAF fusion: 4

References: 31618628

New LY3009120 in Solid tumours with BRAF Oncogenic mutations: 4

Phase 1 dose escalation and expansion study of LY3009120. References: 31645440

New Trametinib in Melanoma with BRAF SKAP2-BRAF fusion: 4

Case report. Partial but non-durable response to trametinib. References: 34167970

New Afatinib + Bevacizumab in Non-small cell lung cancer with EGFR+ERBB2 EGFR:Exon 19 deletion and ERBB2:Amplification: 4

Case report. Resistance to Gefitinib (Acquired) and Osimertinib associated with acquired ERBB2 amplification in a case of exon 19 deletion. Tumour shrinkage to ERBB2 was observed with overall SD of > 6 months following treatment with afatinib + bevacizumab. References: 33663050

New Gefitinib, Osimertinib in Non-small cell lung cancer with EGFR+ERBB2 EGFR:Exon 19 deletion and ERBB2:Amplification: 4

Case report. Resistance to Gefitinib (Acquired) and Osimertinib associated with acquired ERBB2 amplification in a case of exon 19 deletion. Tumour shrinkage to ERBB2 was observed with overall SD of > 6 months following treatment with afatinib + bevacizumab. References: 33663050

New Osimertinib + Pralsetinib in Non-small cell lung cancer with EGFR+RET EGFR:Exon 19 deletion and EGFR:T790M and RET:ANK3-RET fusion: 4

Case report. Acquired resistance of ANK3-RET fusion following treatment to know EGFR mutations. Durable response of >12 months to Osimertinib and Pralsetinib combination. References: 35797511

New Afatinib in Endometrioid endometrial cancer, Endometrial cancer with ERBB2 Amplification: 4

Case report. Partial response observed two months after afatinib. References: 31308701

New Vemurafenib, Dabrafenib, PLX8394 in Melanoma with BRAF Fusions, FKBP15-BRAF fusion, TARDBP-BRAF fusion, AGK-BRAF fusion, SKAP2-BRAF fusion, CUL1-BRAF fusion, KIAA1549-BRAF fusion: R2

References: 31618628

Friday, 2 September 2022 (Version: 20220902AU)

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Colorectal adenocarcinoma with B2M Loss-of-function mutations, loss of protein expression: 4

Retrospective series. In metastatic CRCs, B2M mutations (and loss of B2M expression) are associated with microsatellite high disease and derive clinical benefit from immune checkpoint inhibitors. References: 31008436

New Pembrolizumab in Melanoma with B2M Loss-of-function mutations, deletion: R2

Case series. Acquired B2M mutation leads to loss of MHC class I expression. References: 27433843

New Pembrolizumab in Melanoma with JAK1 Loss-of-function mutations, deletion: R2

Case series. Acquired JAK1/JAK2 loss-of-function mutations resulted in lack of response to IFN-gamma. References: 27433843

New Pembrolizumab in Melanoma with JAK2 Loss-of-function mutations, deletion: R2

Case series. Acquired JAK1/JAK2 loss-of-function mutations resulted in lack of response to IFN-gamma. References: 27433843

Wednesday, 31 August 2022 (Version: 20220831AU)

New Pemigatinib in Myelodysplastic/myeloproliferative diseases, Myeloproliferative diseases, Acute lymphoblastic leukaemia, Acute myeloid leukaemia with FGFR1 Rearrangement, Fusion: 2

Not TGA approved. FDA approved. Phase 2. FIGHT-203. NCT03011372. CR was achieved in 14 of 18 patients with chronic phase (78%) and 2 in 4 patients with blast phase in the marrow. 22 of 28 patients (79%) achieved complete cytogenetic response. References:

New PF-9363 in Breast cancer with KAT6A Amplification, Overexpression: 4

References: 10.1158/1538-7445.AM2021-1130

Tuesday, 30 August 2022 (Version: 20220830AU)

New Ceralasertib + Olaparib in Solid tumours with ATM Oncogenic mutations: 4

Xenograft study. References: 32444694

New Neratinib + Alpelisib in Breast cancer with ERBB2+ERBB3 ERBB2:Oncogenic mutation and ERBB3:E928G, ERBB2:S310F and ERBB3:E928G, ERBB2:L755S and ERBB3:E928G, ERBB2:V777L and ERBB3:E928G, ERBB2:L869R and ERBB3:E928G: 4

Cell-line study. HER2/HER3 co-mutations activate PI3K signaling pathways in tumour cells, resulting in resistance to HER2 inhibitors. The co-operative activation of HER2/HER2 is sensitive to combined inhibition with Both HER2 and PI3K inhibitors. References: 34171264

New Afatinib, Trastuzumab + Lapatinib in Solid tumours with ERBB3 E928G, Q865H, S864I: 4

Case series. Treatment with lapatinib and afatinib resulted in prolonged PFS ratio in one case each of breast cancer, cholangiocarcinoma, and lung squamous cell carcinoma. The benefits seen were in cases where simple mutations occur at the ERBB3 kinase domain. References: 29413684

New Neratinib, Trastuzumab + Pertuzumab, Trastuzumab in Breast cancer with ERBB2+ERBB3 ERBB2:Oncogenic mutation and ERBB3:E928G, ERBB2:S310F and ERBB3:E928G, ERBB2:L755S and ERBB3:E928G, ERBB2:V777L and ERBB3:E928G, ERBB2:L869R and ERBB3:E928G: R2

Cell-line study. HER2/HER3 co-mutations activate both ERBB and PI3K signaling pathways in tumour cells, resulting in resistance to HER2 inhibitors. References: 34171264

Sunday, 28 August 2022 (Version: 20220828AU)

Changed Olaparib in Prostate cancer with BRCA1 Oncogenic mutations

Tier changed: 1B. Comments changed: TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control)TGA Approved. Not PBS reimbursed. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). FoundationOne Cdx.

Changed Olaparib in Prostate cancer with BRCA2 Oncogenic mutations

Tier changed: 1B. Comments changed: TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control).TGA Approved. Not PBS reimbursed. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control)..

Friday, 26 August 2022 (Version: 20220826AU)

New Trastuzumab + Tucatinib in Colorectal adenocarcinoma with ERBB2 Amplification, Overexpression: 3

Phase 2. Single-arm study. MOUNTAINEER. NCT03043313. N=84. In metastatic CRC after two-lines of systemic treatment, the tucatinib and trastuzumab combination resulted in ORR of 38% (Cohorts A + B). Median DOR was 12.4 months. Median PFS 8.2 months. Median OS was 24.1 months at follow-up of 20.7 months. References: 10.1016/j.annonc.2022.04.440

New Tucatinib in Colorectal adenocarcinoma with ERBB2 Amplification, Overexpression: R2

Phase 2. Single-arm study. MOUNTAINEER. NCT03043313. N=31. ORR was 3% in tucatinib monotherapy in metastatic CRC after two-lines of systemic treatment (Cohort C). References: 10.1016/j.annonc.2022.04.440

New Ado-Trastuzumab Emtansine in Solid tumours except Breast cancer, Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification, Overexpression: R2

Phase 2. NCT02465060. NCI-MATCH trial (EAY131) subprotocol Q. In 36 patient (of 38) included in efficacy analysis, ORR was 6% (2/36, one salivary gland mucoepidermoid carcinoma and one salivary gland squamous cell cancer) and did not meet the prespecified criteria. PFS at 6-month was 23.6%. References: 31504139

Changed Ado-Trastuzumab Emtansine + Pertuzumab in Colorectal adenocarcinoma with ERBB2 Amplification, Overexpression: R2

Comments changed: Phase 2. NCT03225937. HERACLES-B. N=31. The combination did not reach the primary endpoint (ORR 9.7%), but DCR 77.4% with median PFS 4.1mo.Phase II HERACLES-B. N=31. The combination did not reach the primary endpoint (ORR 9.7%), but DCR 77.4% with median PFS 4.1mo..

Wednesday, 24 August 2022 (Version: 20220824AU)

New Ripretinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation, Exon 9 mutation, Exon 13 mutation, Exon 17 mutation: 3

Biomarker analysis from phase 3 INVICTUS trial. NCT03353753. Ripretinib showed significant longer PFS and OS over placebo across GIST harbouring KIT mutations in exons 9, 11, 13, 17. References: 34503977

Changed Encorafenib + Cetuximab with BRAF V600E: 1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab, Panitumumab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed FOLFIRI + Cetuximab with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed FOLFOX + Panitumumab with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with Mismatch repair Deficient: 1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with Mismatch repair Deficient: 1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with Microsatellite Instability High: 1B

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with Microsatellite Instability High: 1B

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Binimetinib + Encorafenib + Cetuximab with BRAF V600E: 2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Dabrafenib + Trametinib with BRAF V600E: 2

Cancer type(s) changed: Solid tumours except Colorectal adenocarcinoma, melanoma, thyroid cancerSolid tumours except Colorectal cancer, melanoma, thyroid cancer

Changed Ipilimumab + Nivolumab with Microsatellite Instability High: 2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Nivolumab with Microsatellite Instability High: 2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Ipilimumab + Nivolumab with Mismatch repair Deficient: 2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Nivolumab with Mismatch repair Deficient: 2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Vemurafenib with BRAF V600: 3

Cancer type(s) changed: Anaplastic ganglioglioma, Anaplastic thyroid cancer, Cholangiocarcinoma, Biliary tract cancer, Erdheim-Chester disease, High-grade glioma, Langerhans cell histiocytosis, Low-grade glioma, Non-small cell lung cancer, Neuroendocrine carcinoma, Ovarian cancer, Salivary gland cancers, Sarcoma, Solid tumours except Colorectal adenocarcinoma, pancreatic adenocarcinomaAnaplastic ganglioglioma, Anaplastic thyroid cancer, Cholangiocarcinoma, Biliary tract cancer, Erdheim-Chester disease, High-grade glioma, Langerhans cell histiocytosis, Low-grade glioma, Non-small cell lung cancer, Neuroendocrine carcinoma, Ovarian cancer, Salivary gland cancers, Sarcoma, Solid tumours except colorectal cancer, pancreatic adenocarcinoma

Changed Vemurafenib + Cobimetinib with BRAF V600: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab + Irinotecan + Vemurafenib with BRAF V600E: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Dabrafenib + Trametinib with BRAF V600E: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Panitumumab + Dabrafenib + Trametinib with BRAF V600E: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Encorafenib + Binimetinib with BRAF V600E, V600K: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Lapatinib + Trastuzumab with ERBB2 Amplification: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Trastuzumab + Pertuzumab with ERBB2 Amplification: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Trastuzumab + Pertuzumab with ERBB2 ERBB2:amplification: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Fam-trastuzumab deruxtecan-nxki with ERBB2+KRAS ERBB2:Amplification and ERBB2:Protein expression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E, ERBB2:Overexpression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed FOLFOXIRI + Bevacizumab + Atezolizumab with Immunoscore IC High: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Adagrasib with KRAS G12C: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Adagrasib + Cetuximab with KRAS G12C: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Adagrasib with KRAS G12C: 3

Cancer type(s) changed: Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumoursNon-small cell lung cancer, Colorectal cancer, Solid tumours

Changed Panitumumab + Fluorouracil with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Temozolomide + Ipilimumab + Nivolumab with MGMT Loss of protein expression, Promoter methylation: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed FOLFOXIRI + Bevacizumab + Atezolizumab with Mismatch repair Deficient: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Nivolumab with Mismatch repair Deficient: 3

Cancer type(s) changed: Solid tumours except Colorectal adenocarcinomaSolid tumours except Colorectal cancer

Changed Nivolumab with MLH1 Loss of protein expression: 3

Cancer type(s) changed: Solid tumours except Colorectal adenocarcinomaSolid tumours except Colorectal cancer

Changed Nivolumab with MSH2 Loss of protein expression: 3

Cancer type(s) changed: Solid tumours except Colorectal adenocarcinomaSolid tumours except Colorectal cancer

Changed Adavosertib with TP53+KRAS TP53:Oncogenic mutations AND KRAS:G12, TP53:Oncogenic mutations AND KRAS:G13: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed FOLFOXIRI + Bevacizumab + Atezolizumab with Tumour Mutational Burden High: 3

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with Tumour Mutational Burden High: 3

Cancer type(s) changed: Solid tumours except Colorectal adenocarcinomaSolid tumours except Colorectal cancer

Changed SM08502 with APC Oncogenic mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Olaparib with ATM Loss-of-function mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab, Panitumumab with BRAF F247L, G466E, G466V, Q524L, R558Q, N581I, N581S, N581T, D594G, D594N, F595L, Class III mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Belvarafenib with BRAF V600E: 4

Cancer type(s) changed: Melanoma, Colorectal adenocarcinomaMelanoma, Colorectal cancer

Changed Encorafenib + Capmatinib with BRAF+MET Amplification: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Prexasertib with CHEK1 Overexpression: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Capecitabine + Bevacizumab with Consensus molecular subtype CMS2, CMS3: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed FOLFIRI + Cetuximab with Consensus molecular subtype CMS4: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Erlotinib with EGFR EGFR-SEPT14 Fusion: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Erlotinib with EGFR EGFR-SEPT14 Fusion: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed MVC-101 with EGFR Protein expression: 4

Cancer type(s) changed: Head and neck squamous cell carcinoma, Non-small cell lung cancer, Colorectal adenocarcinomaHead and neck squamous cell carcinoma, Non-small cell lung cancer, Colorectal cancer

Changed Trastuzumab + Lapatinib with ERBB2 Amplification and S310F: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Fam-trastuzumab deruxtecan-nxki with ERBB2 Amplification; Alteration: 4

Cancer type(s) changed: Gastric cancer, Gastroesophageal junction adenocarcinoma, Colorectal adenocarcinomaGastric cancer, Gastroesophageal junction adenocarcinoma, Colorectal cancer

Changed Ado-Trastuzumab Emtansine with ERBB2 ERBB2:amplification and KRAS:G12D: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed ERBB2 inhibitor with ERBB2 Exon 21 mutation: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Ado-Trastuzumab Emtansine with ERBB2+KRAS ERBB2:amplification and KRAS:G12D: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed H3Mab-17 with ERBB3 Overexpression: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Regorafenib + ABT-737 with FBXW7 Oncogenic mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed BMS-754807 with IRS2 Amplification: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Sotorasib with KRAS G12C: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed JAB-21822 with KRAS G12C: 4

Cancer type(s) changed: Non-small cell lung cancer, Colorectal adenocarcinomaNon-small cell lung cancer, Colorectal cancer

Changed Lifirafenib with KRAS Oncogenic mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Onvansertib + FOLFIRI + Bevacizumab, Onvansertib with KRAS Oncogenic mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Selumetinib + Irinotecan with KRAS Oncogenic mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Afatinib + Selumetinib with KRAS+ERBB3 KRAS:Oncogenic mutations and ERBB3:Overexpression: 4

Cancer type(s) changed: Non-small cell lung cancer, Colorectal adenocarcinomaNon-small cell lung cancer, Colorectal cancer

Changed Crizotinib in Non-small cell lung cancer, Small-cell lung cancer: 4

Biomarker changed: MET1. Alterations changed: CAV1-MET fusionCAV-MET1 fusion.

Changed Atezolizumab with Microsatellite Instability High: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed TetMYB with MYB Alteration; Overexpression: 4

Cancer type(s) changed: Solid tumours, Adenoid cystic carcinoma, Colorectal adenocarcinomaSolid tumours, Adenoid cystic carcinoma, Colorectal cancer

Changed Berzosertib with POLD1 Loss of protein expression: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with POLE P286R: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed RXC004 with RNF43 Oncogenic mutations: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed RXC004 with RSPO1 Fusion: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with Tumour Mutational Burden High: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody with Tumour Mutational Burden High: 4

Cancer type(s) changed: Solid tumours except Colorectal adenocarcinomaSolid tumours except Colorectal cancer

Changed Durvalumab + Tremelimumab with Tumour Mutational Burden+Microsatellite Tumour Mutational Burden:High and Microsatellite:Stable: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Durvalumab + Tremelimumab with Tumour Mutational Burden+Mismatch repair Tumour Mutational Burden:High and Mismatch repair:Proficient: 4

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed IK-930 in Epithelioid haemangioendothelioma: 4

Biomarker changed: WWTR1TAZ. Alterations changed: WWTR1-CAMTA1 fusion, fusionTAZ-CAMTA1 fusion, fusion.

Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab with BRAF V600E: R1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab with KRAS Oncogenic mutations: R1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab with NRAS Oncogenic mutations: R1

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab, Panitumumab with BRAF G469A, G469V, L485F, L525R, L597R, T599_V600TinsT, K601E, Class II mutations: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Vemurafenib with BRAF V600: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Vemurafenib with BRAF V600: R2

Cancer type(s) changed: Pancreatic adenocarcinoma, Colorectal adenocarcinomaPancreatic adenocarcinoma, Colorectal cancer

Changed Lapatinib + Trastuzumab with BRAF V600E: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Trastuzumab + Pertuzumab with BRAF V600E: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab with BRAF+MET Amplification: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Erlotinib with EGFR EGFR-SEPT14 Fusion: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Ado-Trastuzumab Emtansine + Pertuzumab with ERBB2 Amplification, Overexpression: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab, Panitumumab, Cetuximab + Irinotecan with ERBB2 Amplification, Overexpression: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Fam-trastuzumab deruxtecan-nxki with ERBB2 No protein expression, Low protein expression: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Trastuzumab + Pertuzumab with ERBB2+KRAS ERBB2:amplification and KRAS:G12: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Regorafenib with FBXW7 Oncogenic mutations, S668fs*39, L403fs*34, R505C, R505H, R465C, R479Q, G579W, R658Q: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab with HRAS G13D: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed BMS-754807 with IRS2+BRAF IRS2:Amplification AND BRAF:V600E: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed BMS-754807 with IRS2+KRAS IRS2:Amplification AND KRAS:G13D: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Binimetinib + Encorafenib with KRAS Amplification: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab, Panitumumab with KRAS Amplification: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab, Panitumumab with KRAS Amplification: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Dabrafenib + Panitumumab with KRAS Amplification: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Sotorasib with KRAS G12C: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Cetuximab, Cetuximab + Irinotecan with KRAS G13D: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Afatinib with KRAS Oncogenic mutations: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Lapatinib + Trastuzumab with KRAS Oncogenic mutations: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with KRAS+Microsatellite Instability KRAS:Oncogenic mutations AND Microsatellite Instability:High: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Pembrolizumab with KRAS+Mismatch repair KRAS:Oncogenic mutations AND Mismatch repair:deficient: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Duligotuzumab + FOLFIRI with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Dabrafenib + Trametinib, Trametinib with MAP2K1 F53L: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed Atezolizumab, Atezolizumab + Cobimetinib with Microsatellite Instability Stable: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed MK2206 with PIK3CA Oncogenic mutations: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Changed MK2206 with PTEN Loss of protein expression: R2

Cancer type(s) changed: Colorectal adenocarcinomaColorectal cancer

Saturday, 13 August 2022 (Version: 20220813AU)

Changed Fam-trastuzumab deruxtecan-nxki in Non-small cell lung cancer with ERBB2 S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, G778_P780dup, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation: 2

Comments changed: Not TGA approved. FDA approved. DESTINY-Lung01. Phase 1/2. N=91. ORR 50/91 (55%). Median DOR 9.3 months. Median PFS 8.2 months. Median OS 17.8 months. DCR 84/91 (92%)..

Friday, 12 August 2022 (Version: 20220812AU)

New SHP099 + Trametinib in Solid tumours with BRAF V600E: 4

References: 30605687

New AMX-818 in Solid tumours with ERBB2 Overexpression, Protein expression, Low protein expression: 4

References: 10.1158/1535-7163.TARG-21-P193

New SHP099 + Trametinib in Solid tumours with KRAS G12C, G12A, G12S, G12: 4

Cell line study. TNBC and RAS G12 tumours are known to be sensitive to combined SHP2-MEK inhibition in cell line models. References: 30605687

New SHP099, SHP099 + Trametinib in Solid tumours with KRAS G13D, Q61K, Q61R: R2

Cell line study. RAS G13D and Q61X predict resistance to SHP2 inhibitors. References: 30605687

Changed Entrectinib in Non-small cell lung cancer with ROS1 Fusions: 1

Comments changed: PBS reimbursed. ROS1-positivity is defined as gene rearrangement >15% positive cells by FISH. In combined analysis of ALKA-372-001, STARTRK-1, and STARTRK-2, ORR was 71% wit hmedian DOR of 24.6 months.. References changed: 28183697, 31838015, 10.1200/jco.2015.33.15_suppl.251728183697, 10.1200/jco.2015.33.15_suppl.2517.

Changed Capmatinib in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 2

Comments changed: Not TGA approved; FDA approved 10/8/2022; GEOMETRY mono-1: ORR 41% in 69 previously treated patients. Median DOR 9.7 months. ORR 68% in 28 treatment naive patients. Median DOR 12.6 months.Not TGA approved; FDA approved; GEOMETRY mono-1: ORR 41% in 69 previously treated patients. Median DOR 9.7 months. ORR 68% in 28 treatment naive patients. Median DOR 12.6 months..

Changed AMG-650 in Solid tumours with TP53 Oncogenic mutations: 4

Comments changed: Cell line study. Targeting KIF18A in has shown mitotic arrest in MDA-MB-157 cell lines. Ongoing phase 1 trial NCT04293094.. References changed: 35286090, 10.1200/JCO.2021.39.15_suppl.TPS5600.

Wednesday, 10 August 2022 (Version: 20220810AU)

New Imatinib in Glioblastoma with ABL1 BCR-ABL1 Fusion: 4

Case report. Treatment with imatinib in a Glioblastoma harbouring BCR-ABL1 fusion resulted decrease in KI-67 and clinical stable disease. References: 34485806

New Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab in Colorectal cancer with HRAS G13D: R2

Case report and cell line study. A single case report of metastatic colorectal cancer harbouring HRAS G13D mutation, showing lack of response to Panitumumab. HRAS mutations constitute 1% of colorectal cancer. References: 26561417

New Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer with RET Y806C, G810C, G801S: R2

References: 35304457

Changed Therapy in Colorectal cancer with KRAS Oncogenic mutations: R1

Therapy changed: Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + PanitumumabPanitumumab, Cetuximab, Cetuximab + Irinotecan.

Changed Therapy in Colorectal cancer with NRAS Oncogenic mutations: R1

Therapy changed: Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + PanitumumabPanitumumab, Cetuximab, Cetuximab + Irinotecan.

Saturday, 6 August 2022 (Version: 20220806AU)

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification; Overexpression: 1B

Comments changed: Not TGA approved. FDA approved. DESTINY-Breast01: In patients with prior anti-HER2 therapies, median DOR 14.8mo, PFS 16.4mo. HER2 positivity: defined as IHC 3+ or FISH positive..

Changed Crizotinib in Inflammatory myofibroblastic tumour with ALK Fusions, RANBP2-ALK Fusion: 2

Comments changed: Not TGA approved. FDA approved 14/7/2022..

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 2

Comments changed: Not TGA approved. Phase 3. DESTINY-Breast04. NCT03734029. Compared with physician’s choice, T-DXD prolonged both PFS (10.1 v 5.4 months) and OS (23.9 v 17.5 months) in Hormone receptor-positive, HER2-low metastatic breast cancer. Similarly T-DXD also prolonged PFS (9.9 v 5.1 months) and OS (23.4 vs 16.8 months) compared to physician’s choice in the overall population. HER2-Low was defined as IHC a score of 1+ or 2+ with negative results on in situ hybridization. FDA approved 5/8/2022..

Wednesday, 3 August 2022 (Version: 20220803AU)

New CX-5461, Quarfloxin in Neuroblastoma with MYCN Amplification: 4

Cell line and Xenograft studies. In neuroblastoma cell lines, RNA polymerase I inhibitors have been shown to suppress n-myc expression and induced cell cycle arrest and apoptosis. References: 30542116

New SHP099 in Pancreatic acinar cell carcinoma with KRAS Q61H: R2

References: 34725361

Sunday, 31 July 2022 (Version: 20220731AU)

New Ceralasertib + Olaparib in Solid tumours with ATM Oncogenic mutations: 4

Phase 2. NCT02576444. OLAPCO. 1 CR (breast cancer) and 1 prolonged SD (26 months) with ATM germline mutations seen in 5 cases. References: 34527850

Saturday, 30 July 2022 (Version: 20220730AU)

New Docetaxel + Trastuzumab in Breast cancer with ERBB2 Amplification, Overexpression: 1

References: 15911866

Thursday, 28 July 2022 (Version: 20220728AU)

Changed Crizotinib in Non-small cell lung cancer with MET : 3

Alterations changed: Amplification, D1010 (D1028), Exon 14 Deletion, Exon 14 splicing mutation, Y1003 (Y1021)Amplification, D1010, Exon 14 Deletion, Exon 14 splicing mutation, Y1003.

Changed Crizotinib in Non-small cell lung cancer with MET : 4

Alterations changed: D1028H (D1010H).

Changed Crizotinib in Non-small cell lung cancer with MET : 4

Alterations changed: D1028N (D1010N).

Changed Cabozantinib in Non-small cell lung cancer with MET : 4

Alterations changed: Exon 14 deletion, Exon 14 splicing mutation, Exon 14 skipping mutation, Y1003 (Y1021), D1010 (D1028), Amplification, D1228, G1163Exon 14 deletion, Exon 14 splicing mutation, Exon 14 skipping mutation, Y1003, D1010, Amplification, D1228, G1163.

Changed Crizotinib in Non-small cell lung cancer with MET : 4

Alterations changed: Y1003S (Y1021S).

Changed Crizotinib in Non-small cell lung cancer with MET : 4

Alterations changed: Y1021H (Y1003H).

Changed Cabozantinib in Gastrointestinal stromal tumour with MET : 4

Alterations changed: Y1248H (Y1230H), D1246N (D1228N), K1262R (K1244R)Y1248H, D1246N, K1262R.

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: D1228N (D1246N).

Changed Crizotinib in Triple-negative breast cancer with MET : R2

Alterations changed: D1228N (D1246N).

Changed Capmatinib, Tepotinib, Savolitinib in Non-small cell lung cancer with MET : R2

Alterations changed: D1228N (D1246N), D1228 (D1246)D1228N, D1228.

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: D1246N (D1228N).

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: F1007fs (F1025fs).

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: G1163R (G1181R), D1228H (D1246N), D1228A (D1246A), Y1230H (Y1248A)G1163R, D1228H, D1228A, Y1230H.

Changed Glesatinib in Non-small cell lung cancer with MET : R2

Alterations changed: H1094Y (H1112Y), L1195V (L1213V)H1094Y, L1195V.

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: L1195V (L1213V), Y1230 (Y1248), D1228N (D1246N), D1228 (D1246), D1246 (D1228), Y1248 (Y1230), G1163 (G1181)L1195V, Y1230, D1228N, D1228, D1246, Y1248, G1163.

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: Y1230C (Y1248C).

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: Y1230H (Y1248H).

Changed Crizotinib in Non-small cell lung cancer with MET : R2

Alterations changed: Y1230S (Y1248S), D1228N (D1246N), D1228H (D1246H), F1200I (F1218I), L1195V (L1213V), S244fsY1230S, Y1230H, D1228N, D1228H, F1200I, L1195V, S244fs.

Wednesday, 27 July 2022 (Version: 20220727AU)

New Imatinib in T-cell acute lymphoblastic leukaemia with ABL1 NUP214-ABL1 fusion: 3

Case series. Nine of 11 complete responders seen in T-cell ALLs with extrachromosomal NUP214-ABL1 fusion treated with imatinib. References: 15361874

New Erdafitinib, Pemigatinib in Solid tumours with FGFR2 K660M: 4

References: 32973082

New Futibatinib in Solid tumours with FGFR2 N550H, V565I, V565L, E566G, K660M: 4

In cell line studies, futibatinib is active several drug-resistant FGFR2 mutants including V565I gatekeeper mutants. References: 32973082

New Sorafenib in Thymic carcinoma with KIT Exon 11 mutation: 4

References: 20970876

New Sorafenib in Thymic carcinoma with KIT Exon 11 mutation, Exon 11 deletion, V560del: 4

References: 15201427

New Imatinib in Thymic carcinoma with KIT Exon 11 mutation, Y553N: 4

References: 21969494

New Sorafenib in Thymic carcinoma with KIT Exon 17 mutation, D820E: 4

References: 19461405

New Imatinib in Thymic neuroendocrine carcinoma with KIT Overexpression: 4

Case series. Responses to imatinib seen In two CD117 positive atypical thymic carcinoid. No KIT mutations in both cases. References: 20876428

New SAR442720 in Solid tumours with KRAS Amplification: 4

References: NCT04418661

New AZD4547, Infigratinib in Solid tumours with FGFR2 N550H, V565I, V565L, E566G, K660M: R2

In cell line studies, futibatinib is active several drug-resistant FGFR2 mutants including V565I gatekeeper mutants. References: 32973082

New Cabozantinib + Nivolumab in Non-clear cell renal cell carcinoma with SETD2 Truncating mutations: R2

NCT03635892. Single arm in Non-clear cell renal cell carcinomas. In non-chromophobe group, the overall ORR was 48%. In exploratory biomarker analysis, SETD2 truncating mutation was associated with reduced response with Cabozantinib and Nivolumab (0 of 5 cases). References: 35298296

Changed Cabozantinib + Nivolumab in Papillary renal cell carcinoma with FH Oncogenic mutations: 4

Comments changed: Phase 2. NCT03635892. Single arm trial in non-clear cell renal cell carcinomas with ORR of 48%. Responses were seen in 10 of 12 patients with either NF2 or FH mutations. In exploratory biomarker analysis, FH mutation was associated with response with Cabozantinib and Nivolumab (5 of 6 cases).Phase 2. NCT03635892. Responses were seen in 10 of 12 patients with either NF2 or FH mutations..

Changed Cabozantinib + Nivolumab in Papillary renal cell carcinoma, Sarcomatoid renal cell carcinoma with NF2 Oncogenic mutations, Truncating mutations: 4

Comments changed: Phase 2. NCT03635892. Single arm trial in non-clear cell renal cell carcinomas with ORR of 48%. Responses were seen in 10 of 12 patients with either NF2 or FH mutations. In exploratory biomarker analysis, NF2 mutations were associated with response with Cabozantinib and Nivolumab (5 of 6 cases).Phase 2. NCT03635892. Responses were seen in 10 of 12 patients with either NF2 or FH mutations..

Changed Therapy in Colorectal cancer with BRAF V600E: R1

Therapy changed: Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab.

Tuesday, 26 July 2022 (Version: 20220726AU)

New Futibatinib in Cholangiocarcinoma with FGFR2 Fusion, FGFR2-POC1B fusion, FGFR2 rearrangement, C383R, W290C,: 3

NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14% (25% in cholangiocarcinoma). In the 20 mg daily dose cohort (N=64), ORR was 16% and DCR was 72%. DOR 5.3 months. In the 16 mg cohort (N=16), ORR was 42% (8/19). Responders included patients previously treated with other FGFR inhibitors. References: 34551969

New Futibatinib in Solid tumours with FGFR1 FGFR1-PLAG1 fusion, FGFR1-TACC1 fusion, M563T: 4

NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14%. Responses were seen in two FGFR1 fusions and one urothelial carcinoma harbouring M563T and FGF3/FGF19 amplification. References: 34551969

New Futibatinib in Solid tumours, Gastric cancer with FGFR2 Amplification: 4

NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14%. Responses was seen single case of gastric cancer harbouring FGFR2 amplification. References: 34551969

New Futibatinib in Solid tumours, Gastric cancer, Urothelial carcinoma with FGFR3 FGFR3-TACC3 fusion, S249C: 4

NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14%. Responses were seen in one case of gastric cancer in FGFR3-TACC3 fusion and two cases of urothelial carcinoma harbouring S249C. References: 34551969

Thursday, 21 July 2022 (Version: 20220721AU)

Changed Pembrolizumab + Nab-paclitaxel, Pembrolizumab + Paclitaxel, Pembrolizumab + Carboplatin + Gemcitabine in Triple-negative breast cancer with CD274 Protein expression: 2

Comments changed: Not TGA approved. FDA accelerated approval. KEYNOTE-355: First-line pembrolizumab combination with chemotherapy in TNBC with PD-L1 expression (defined as combined positive score of >= 10%). PFS 9.7 v 5.6mo. Median OS was significantly longer in pembrolizumab plus chemotherapy group (23.0 months) versus chemotherapy alone (16.1 months).. References changed: 33278935, 35857659, 10.1200/JCO.2020.38.15_suppl.100033278935, 10.1200/JCO.2020.38.15_suppl.1000.

Wednesday, 20 July 2022 (Version: 20220720AU)

New Dabrafenib + Trametinib in Colorectal cancer with BRAF V600E: 3

Phase 2. NCT01072175. ORR 12% in pretreated CRC with PFS of 3.5 months. References: 26392102

New Crizotinib in Non-small cell lung cancer, Small-cell lung cancer with MET1 CAV-MET1 fusion: 4

Case report. Objective response was seen in SCLC transformation with Inframe fusion of exons 1-2 of CAV1 to exons 2-21 of MET on the background of EGFR L858R. References: 31122565

Monday, 18 July 2022 (Version: 20220718AU)

New Runimotamab in Breast cancer, Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression, Protein expression: 4

Phase 1 trial eligibility. References: NCT03448042

New Runimotamab in Solid tumours with ERBB2 Overexpression, Amplification: 4

Phase 1 trial eligibility. References: NCT03448042

New GQ1001 in Breast cancer, Gastric cancer, Gastroesophageal junction adenocarcinoma, Solid tumours with ERBB2 Overexpression, Protein expression: 4

Phase 1 trial eligibility. References: NCT04450732

New DB-1303, ARX788 in Solid tumours with ERBB2 Overexpression, Protein expression, Amplification: 4

Phase 1 trial eligibility. References: NCT05150691, NCT03255070

New SHR-A1811 in Solid tumours with ERBB2 Overexpression, Protein expression, Oncogenic mutations: 4

Phase 1 trial eligibility. References: NCT04446260

Tuesday, 12 July 2022 (Version: 20220712AU)

New Capmatinib, Capmatinib + Trametinib in Malignant peripheral nerve sheath tumor with NF1+MET NF1:Oncogenic mutation AND MET:Amplification, NF1:Deletion AND MET:Amplification: 4

NF1-MET MPNST are sensitive to capmatinib and/or trametinib in transgenic mouse models. References: 29720369

Friday, 8 July 2022 (Version: 20220708AU)

New Durvalumab + Olaparib in Urothelial carcinoma with ATM Oncogenic mutations: 4

Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint). References: 35737919

New Durvalumab + Olaparib in Urothelial carcinoma with BARD1 Oncogenic mutations: 4

Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint). References: 35737919

New Durvalumab + Olaparib in Urothelial carcinoma with BRCA1 Oncogenic mutations: 4

Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint). References: 35737919

New Durvalumab + Olaparib in Urothelial carcinoma with BRCA2 Oncogenic mutations: 4

Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint). References: 35737919

New Durvalumab + Olaparib in Urothelial carcinoma with BRIP1 Oncogenic mutations: 4

Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint). References: 35737919

New Durvalumab + Olaparib in Urothelial carcinoma with CDK12 Rearrangement: 4

Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint). References: 35737919

New Durvalumab + Olaparib in Urothelial carcinoma with RAD51C Oncogenic mutations: 4

Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint). References: 35737919

Wednesday, 6 July 2022 (Version: 20220706AU)

New Pembrolizumab, Durvalumab, Nivolumab, Nivolumab + Ipilimumab in Solid tumours with CDK12 Oncogenic mutations: 4

Retrospective series. 6 of 10 received immune checkpoint inhibitor experienced objective response. References: 34898046

New Crizotinib in Non-small cell lung cancer with MET D1028H: 4

Case report. c.3082G>C could result in skipping of exon 14. Radiographic response to crizotinib was observed. References: 25898962

New Crizotinib in Non-small cell lung cancer with MET D1028N: 4

Case report. References: 26892698

Friday, 1 July 2022 (Version: 20220701AU)

Changed Larotrectinib with NTRK1 Fusions, ATP1A4-NTRK1 fusion, CD74-NTRK1 fusion, CTRC-NTRK1 fusion, DDR2-NTRK1 fusion, DIAPH1-NTRK1 fusion, EPS15-NTRK1 fusion, GON4L-NTRK1 fusion, IRF2BP2-NTRK1 fusion, LMNA-NTRK1 fusion, NFASC-NTRK1 fusion, PDE4DIP-NTRK1 fusion, PLEKHA6-NTRK1 fusion, PPL-NTRK1 fusion, SQSTM1-NTRK1 fusion, TPM3-NTRK1 fusion, TPR-NTRK1 fusion, TRIM63-NTRK1 fusion

Cancer type(s) changed: Solid tumours, Mammary analogue secretory carcinoma, Breast secretory carcinoma Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed 1/7/22 for paediatric solid tumours and adult mammary analogue secretory carcinoma of salivary gland and secretary breast carcinoma. NCT02122913, NCT02637687, NCT02576431TGA approved. Not PBS reimbursed. NCT02122913, NCT02637687, NCT02576431.

Changed Larotrectinib with NTRK2 Fusions, GNAQ-NTRK2 fusion, RBPMS-NTRK2 fusion, STRN-NTRK2 fusion, TRAF2-NTRK2 fusion

Cancer type(s) changed: Solid tumours, Mammary analogue secretory carcinoma, Breast secretory carcinoma Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed 1/7/22 for paediatric solid tumours and adult mammary analogue secretory carcinoma of salivary gland and secretary breast carcinoma. NCT02122913, NCT02637687, NCT02576431TGA approved. Not PBS reimbursed. NCT02122913, NCT02637687, NCT02576431.

Changed Larotrectinib with NTRK3 Fusions, ARNT2-NTRK3 fusion, EML4-NTRK3 fusion, ETV6-NTRK3 fusion, IQGAP1-NTRK3 fusion, MYO5A-NTRK3 fusion, SPECC1L-NTRK3 fusion, SQSTM1-NTRK3 fusion, TFG-NTRK3 fusion, TPM4-NTRK3 fusion

Cancer type(s) changed: Solid tumours, Mammary analogue secretory carcinoma, Breast secretory carcinoma Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed 1/7/22 for paediatric solid tumours and adult mammary analogue secretory carcinoma of salivary gland and secretary breast carcinoma. NCT02122913, NCT02637687, NCT02576431TGA approved. Not PBS reimbursed. NCT02122913, NCT02637687, NCT02576431.

Tuesday, 28 June 2022 (Version: 20220628AU)

New IK-930 in Solid tumours, Mesothelioma with NF2 Loss-of-function mutations, deletion: 4

References: NCT05228015

New IK-930 in Epithelioid haemangioendothelioma with TAZ TAZ-CAMTA1 fusion, fusion: 4

References: NCT05228015

New IK-930 in Epithelioid haemangioendothelioma with YAP1 YAP1-TFE3 fusion, fusion: 4

References: NCT05228015

Friday, 24 June 2022 (Version: 20220624AU)

New Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600: 2

Not TGA approved. FDA approved 23/06/2022. Study X2101. NCT02124772. In paediatric glioma, treatment with dabrafenib and trametinib combination resulted in ORR of 25%. References: 10.1200/JCO.2020.38.15_suppl.10506

New Tusamitamab ravtansine in Solid tumours with CEACAM5 Protein expression: 4

Phase 1 Dose escalation study. In 31 patients, 3 objective responses were seen in 100-120 mg/m^2 dose levels. CEACAM5 expression level was 2+ in two responders of colorectal cancer. One gastric cancer. References: 35026412

New Ribociclib in Solid tumours with CCND1 Amplification: R2

NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months. References: 10.1200/PO.18.00383

New Ribociclib in Solid tumours with CCND3 Amplification: R2

NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months. References: 10.1200/PO.18.00383

New Palbociclib in Glioblastoma with CDK4 Amplification: R2

References: 22711607

New Ribociclib in Solid tumours with CDK4 Amplification, Oncogenic mutations: R2

NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months. References: 10.1200/PO.18.00383

New Ribociclib in Rhabdomyosarcoma with CDK4 Amplification, Overexpression: R2

Preclinical study. CDK4 amplification/overexpression confer reduced susceptibility to CDK4/6 inhibitors in fusion-positive rhabdomyosarcoma cell-line models. References: 25810375

New Ribociclib in Solid tumours with CDK6 Amplification, Oncogenic mutations: R2

NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months. References: 10.1200/PO.18.00383

New Ribociclib, Abemaciclib in Breast cancer with CDK6 Amplification, Overexpression: R2

Preclinical study. In breast cancer cell line models, amplification of CDK6 acquired after exposure to CDK4/6 inhibitors leads to drug resistance, loss of ER signaling, and decrease responsiveness to endocrine therapy. References: 27748766

New Ribociclib in Solid tumours with CDKN2A Loss-of-function mutations, deletion: R2

NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months. References: 10.1200/PO.18.00383

New Pembrolizumab in High-grade gliomas with Mismatch repair Deficient: R2

N=13. Single-agent PD-1 inhibitor showed no response in a prospective case series (ORR 0%) with 4 SD. References: 32823925

Changed Dabrafenib + Trametinib in Biliary tract cancers with BRAF V600E

Tier changed: 23. Comments changed: Not TGA approved. FDA approval for tumour agnostic indication 23/06/22. ROAR. BICR ORR 47%..

Changed Dabrafenib + Trametinib in Gliomas, High-grade gliomas, Low-grade gliomas with BRAF V600E

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 23/6/22. Phase 2. NCT02034110. In high-grade gliomas: ORR 33% (15/45), including 3 CR. Median PFS 3.8 months. Median OS 17.6 months. In low-grade gliomas: ORR 69% (9/13), including 1 CR. Median PFS and OS not reached..

Changed Dabrafenib + Trametinib in Solid tumours except Colorectal cancer, melanoma, thyroid cancer with BRAF V600E

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 23/6/2022. NCI-MATCH Trial Subprotocol H. N=23. ORR 38%. Colorectal cancer, melanoma, thyroid cancers were excluded..

Changed Therapy in Non-small cell lung cancer with CEACAM5 Overexpression: 4

Therapy changed: Tusamitamab ravtansineSAR408701.

Monday, 20 June 2022 (Version: 20220620AU)

New Dabrafenib + Trametinib in High-grade gliomas with BRAF V600: 3

NCT02684058. Phase 2. Paediatric relapsed/refractory high-grade glioma. ORR was 56%, with median PFS of 9.0 months and DOR of 22.2 months. References: 10.1200/JCO.2022.40.16_suppl.2009

New Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600: 3

Randomised phase 2. NCT02684058. In paediatric low-grade glioma, ORR was 47% (vs chemotherapy 11%) in the first-line setting. CBR 86% (vs chemotherapy 46%). Median PFS 20.1 (vs chemotherapy 7.4 months). References: 10.1200/JCO.2022.40.17_suppl.LBA2002

New LOXO-783 in Solid tumours with PIK3CA H1047R: 4

References: NCT05307705

Sunday, 19 June 2022 (Version: 20220619AU)

New ZEN-3694 + Talazoparib in Triple-negative breast cancer with BRCA1+BRCA2 NOT BRCA1:Oncogenic mutations (germline) and NOT BRCA2:Oncogenic mutations (germline): 3

In germline BRCA-wildtype TNBCs, BET inhibitor ZEN-3694 creates “BRCAness” and renders sensitive to Talazoparib. Activity was demonstrated in the phase 2 portion of the trial met primary endpoint with CBR 30% (11/37). ORR was 22% (11/50) in the combined phase 1b and 2 cohort. References: 10.1200/JCO.2022.40.16_suppl.1023

New Olaparib + Ceralasertib in Triple-negative breast cancer with ATM Loss of protein expression: 4

Phase 2 plasmaMatch Cohort E. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS. References: 10.1200/JCO.2022.40.16_suppl.1024

New Olaparib + Ceralasertib in Triple-negative breast cancer with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 4

Phase 2 plasmaMatch Cohort E. References: 10.1200/JCO.2022.40.16_suppl.1024

New Olaparib + Ceralasertib in Triple-negative breast cancer with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 4

Phase 2 plasmaMatch Cohort E. References: 10.1200/JCO.2022.40.16_suppl.1024

New Olaparib + Ceralasertib in Triple-negative breast cancer with CCNE1 Overexpression: 4

Phase 2 plasmaMatch Cohort E. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS. References: 10.1200/JCO.2022.40.16_suppl.1024

New Lasofoxifene + Abemaciclib in Breast cancer with ESR1 Protein expression, D538G, Y537S: 4

References: 10.1200/JCO.2022.40.16_suppl.1022

New Imlunestrant in Breast cancer with ESR1 Protein expression, Y537, D538, E380, L536: 4

Phase 1. EMBER. In advanced breast cancerpatients, ORR was 8% (6/75). CBR was 40.4% (42/104). In endometriod cancer patients, ORR was 5% (1/20). CBR was 47%. CBR seen regardless of ESR1 mutation. References: 10.1200/JCO.2022.40.16_suppl.1021

New Olaparib + Ceralasertib in Triple-negative breast cancer with RAD51 Low protein expression: 4

Phase 2 plasmaMatch Cohort E. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS. References: 10.1200/JCO.2022.40.16_suppl.1024

Friday, 17 June 2022 (Version: 20220617AU)

New Capivasertib + Fulvestrant in Breast cancer with AKT1 E17K: 3

Phase 2. FAKTION. Biomarker analysis. In expanded pathway altered group (PIK3CA hotspot, AKT1 E17K, and PTEN altered), PFS was significantly prolonged when capiversertib was added to fulvestrant (12.8 months vs placebo, 4.6 months). OS: 38.9 vs 20.0 months. References: 35671774, 10.1200/JCO.2022.40.16_suppl.1005

New Capivasertib + Fulvestrant in Breast cancer with PIK3CA E542K, E545K, H1047L, H1047R: 3

Phase 2. FAKTION. Biomarker analysis. In expanded pathway altered group (PIK3CA hotspot, AKT1 E17K, and PTEN altered), PFS was significantly prolonged when capiversertib was added to fulvestrant (12.8 months vs placebo, 4.6 months). OS: 38.9 vs 20.0 months. References: 35671774, 10.1200/JCO.2022.40.16_suppl.1005

New Fulvestrant + Alpelisib in Breast cancer with PIK3CA+FGFR1 PIK3CA:Oncogenic mutation AND FGFR1:Alteration: 3

Biomarker analysis of SOLAR-1. In PIK3CA and FGFR altered cohort, significant longer PFS was seen in alpelisib 12.7 months vs placebo 3.8 months. References: 10.1200/JCO.2022.40.16_suppl.1006

New Fulvestrant + Alpelisib in Breast cancer with PIK3CA+FGFR2 PIK3CA:Oncogenic mutation AND FGFR1:Alteration: 3

Biomarker analysis of SOLAR-1. In PIK3CA and FGFR altered cohort, significant longer PFS was seen in alpelisib 11.0 months vs placebo 9.6 months. References: 10.1200/JCO.2022.40.16_suppl.1006

New Capivasertib + Fulvestrant in Breast cancer with PTEN Alteration: 3

Phase 2. FAKTION. Biomarker analysis. In expanded pathway altered group (PIK3CA hotspot, AKT1 E17K, and PTEN altered), PFS was significantly prolonged when capiversertib was added to fulvestrant (12.8 months vs placebo, 4.6 months). OS: 38.9 vs 20.0 months. References: 35671774, 10.1200/JCO.2022.40.16_suppl.1005

New AZD9833, Elacestrant, Tamoxifen in Breast cancer with ESR1 F404L: 4

plasmaMATCH. Treatment emergent mutation causing acquired resistance at the ligand binding domain. In cell line model, F404L is sensitive to tamoxifen and select SERDs. References: 10.1200/JCO.2022.40.16_suppl.1009

New Fulvestrant in Breast cancer with ESR1 F404L, F404I, F404V: R2

plasmaMATCH. Treatment emergent mutation causing acquired resistance at the ligand binding domain. References: 10.1200/JCO.2022.40.16_suppl.1009

New Ribociclib, Palbociclib, Abemaciclib in Breast cancer with RB1 Heterozygous deletion, Copy number loss, Loss-of-function mutation: R2

Heterozygous loss of RB1 is associated with decreased PFS on CDK4/6 inhibitor and endocrine therapy. References: 10.1200/JCO.2022.40.16_suppl.1010

Thursday, 16 June 2022 (Version: 20220616AU)

New Brigatinib in Non-small cell lung cancer with ALK Fusion AND Amplification, L1196M, E1408V, T1151M: 4

References: 10.1200/JCO.2017.35.15_suppl.9065

New Zenocutuzumab in Solid tumours with NRG1 CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion: 3

Updated results from phase 1/2 eNRGy trial. N=110. ORR 34% (27/84), including 42% in PDAC and 35% in NSCLC. Median DOR 9.1 months. References: 10.1200/JCO.2022.40.16_suppl.105

New Tebentafusp, Tebentafusp + Durvalumab, Tebentafusp + Durvalumab + Tremelimumab in Melanoma with HLA-A2 A*02:01: 3

IMCgp100-201 and IMCgp100-202. PD-1 resistant or refractory cutaneous melanoma. N=230. ORR by RECIST was 10% (IMCgp100-201) and 12% (IMCgp100-202) respectively. The 1 year OS rate of tebentafusp and durvalumab combination was 73%. References: 10.1200/JCO.2022.40.16_suppl.104

Tuesday, 14 June 2022 (Version: 20220614AU)

Changed Nimotuzumab + Gemcitabine in Pancreatic adenocarcinoma with KRAS : 2

Alterations changed: NOT oncogenic mutationsNOT KRAS:oncogenic mutation.

Monday, 13 June 2022 (Version: 20220613AU)

New Vemurafenib + Cobimetinib in Solid tumours with BRAF V600E: 3

Phase 2. TAPUR. NCT02693535. Across many tumour types, ORR was 57%, DCR was 68%, and DOR was 20.5 weeks. PFS 5.8 months. References: 10.1200/JCO.2022.40.16_suppl.3008

New Erdafitinib in Solid tumours with FGFR1 Oncogenic mutations: 3

Phase 2. RAGNAR. NCT04083976. Across FGFR1-3 alterations (mutations and fusions) treated with erdafitinib, ORR was 29% (52/178, including 3 CR) by independent review committee, DCR was 73% (129/178). Median DOR 7.1 months. PFS 5.2 months. OS 10.9 months. ORR was comparable with FGFR mutations vs fusions (26-27%). References: 10.1200/JCO.2022.40.16_suppl.3007

New Erdafitinib in Solid tumours with FGFR2 Fusions, Oncogenic mutations: 3

Phase 2. RAGNAR. NCT04083976. Across FGFR1-3 alterations (mutations and fusions) treated with erdafitinib, ORR was 29% (52/178, including 3 CR) by independent review committee, DCR was 73% (129/178). Median DOR 7.1 months. PFS 5.2 months. OS 10.9 months. ORR was comparable with FGFR mutations vs fusions (26-27%). References: 10.1200/JCO.2022.40.16_suppl.3007

New Erdafitinib in Solid tumours with FGFR3 Fusions, Oncogenic mutations: 3

Phase 2. RAGNAR. NCT04083976. Across FGFR1-3 alterations (mutations and fusions) treated with erdafitinib, ORR was 29% (52/178, including 3 CR) by independent review committee, DCR was 73% (129/178). Median DOR 7.1 months. PFS 5.2 months. OS 10.9 months. ORR was comparable with FGFR mutations vs fusions (26-27%). References: 10.1200/JCO.2022.40.16_suppl.3007

New BI907828 in Dedifferentiated liposarcoma with MDM2+TP53 MDM2:Amplification AND NOT TP53:Oncogenic mutations: 3

DCR was 28/32. ORR was 12.5%. PFS: 8 months. References: 10.1200/JCO.2021.39.15_suppl.3016, 10.1200/JCO.2022.40.16_suppl.3004

New BI907828 in Well-differentiated liposarcoma with MDM2+TP53 MDM2:Amplification AND NOT TP53:Oncogenic mutations: 3

DCR was 100%. ORR was 27%. with prolonged duration of response. References: 10.1200/JCO.2021.39.15_suppl.3016, 10.1200/JCO.2022.40.16_suppl.3004

New Seribantumab in Solid tumours, Non-small cell lung cancer with NRG1 Fusions, ATP1B1-NRG1 fusion, CD74-NRG1 fusion, ITGB1-NRG1 fusion, SDC4-NRG1 fusion, SLC3A2-NRG1 fusion, ITGB1-NRG1 fusion: 3

Phase 2. Cohort 1. In 12 of 15 patients (14 NSCLC patients, 1 pancreatic cancer) with evaluable disease, ORR was 33% (4/12, including 2 CR), and DCR was 92% (11/12). References: 10.1200/JCO.2022.40.16_suppl.3006

New Berzosertib + Irinotecan in Pancreatic adenocarcinoma with ATM Oncogenic mutations: 4

Phase 2. NCT02595931. 2 responders seen in 52 patients. Both patients habour deleterious ATM mutations (E11828 and K1109*, R3008H and R1882* germline). References: 10.1200/JCO.2022.40.16_suppl.3012

New Ulixertinib in Low-grade gliomas, High-grade gliomas, Glioneuronal tumour with BRAF V600E, Fusion: 4

Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%. Prolonged disease control (over 6 months) was seen seen in 3 patients with BRAF fusions. References: 10.1200/JCO.2022.40.16_suppl.3009

New CX-5461 in Small-cell lung cancer with MYCL Overexpression: 4

References: 27298335

New Enfortumab Vedotin in Solid tumours with NECTIN4 Protein expression: 4

References: 32031899

New FCN-159 in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 4

Phase 1. NCT04954001. Adult patient population. Using ReiINS criteria, 16/16 patients showed decreased tumour volume with 6/16 (38%) had tumor size reduction by at least 20%. References: 10.1200/JCO.2022.40.16_suppl.3011

New Ulixertinib in Low-grade gliomas, High-grade gliomas with BRAF V600E: R2

Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%. References: 10.1200/JCO.2022.40.16_suppl.3009

New Ulixertinib in Solid tumours with KRAS Oncogenic mutations: R2

Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%. References: 10.1200/JCO.2022.40.16_suppl.3009

New Ulixertinib in Solid tumours with NF1 Oncogenic mutations: R2

Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%. References: 10.1200/JCO.2022.40.16_suppl.3009

New Ulixertinib in Rhabdomyosarcoma with NRAS Oncogenic mutations: R2

Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%. References: 10.1200/JCO.2022.40.16_suppl.3009

New Vismodegib in Solid tumours with PTCH1 Oncogenic mutations: R2

Phase 2. NCT02465060. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol T. N=34. In 22 of 31 evaluable and MATCH confirmed patient, ORR was 9.1% with 6 month PFS of 22%. In all 31 evaluable patients, ORR was 7% (2/31). References: 10.1200/JCO.2022.40.16_suppl.3010

New Vismodegib in Solid tumours with SMO P641A, W535L, L412F: R2

Phase 2. NCT02465060. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol T. N=34. In 22 of 31 evaluable and MATCH confirmed patient, ORR was 9.1% with 6 month PFS of 22%. In all 31 evaluable patients, ORR was 7% (2/31). References: 10.1200/JCO.2022.40.16_suppl.3010

Removed BI907828 in Dedifferentiated liposarcoma with MDM2 alterations Amplification: Tier 4

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification, Overexpression

Tier changed: 1B2.

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification; Overexpression

Tier changed: 1B2.

Changed PC14586 in Solid tumours with TP53 Y220C: 4

Comments changed: PYNNACLE trial. NCT04585750. ORR was 8/31 (32%) in the 1150mg BD cohort across tumour types.. References changed: 10.1158/1538-7445.AM2021-LB006, 10.1200/JCO.2022.40.16_suppl.3003.

Thursday, 9 June 2022 (Version: 20220609AU)

New Tazemetostat in Atypical teratoid rhabdoid tumor, Chordoma, Epithelioid sarcoma with SMARCB1 Loss of protein expression, Oncogenic mutations: 3

NCT02601937. Phase 1 (Paediatric). N=47. ORR was 17% (2 CR and 6 PR) in INI-negative tumours in the pediatric population (atypical teratoid rhabdoid tumor, chordoma and epithelioid sarcoma). References: 10.1200/JCO.2020.38.15_suppl.10525

New Tazemetostat in Solid tumours with EZH2 Oncogenic mutations: 4

Pediatric MATCH Treatment Trial. References: NCT03213665

New Pembrolizumab in Malignant rhabdoid tumor with SMARCA4 Loss of protein expression: 4

Case report. Response seen in thoracic MRT with prolonged clinical benefit and durable response (11+ months). Concomitant SMARCA2 loss of expression was also identified. References: 31114851

New Tazemetostat in Solid tumours with SMARCA4 Oncogenic mutations: 4

Pediatric MATCH Treatment Trial. References: NCT03213665

New Tazemetostat in Solid tumours with SMARCB1 Oncogenic mutations: 4

Pediatric MATCH Treatment Trial. References: NCT03213665

Wednesday, 8 June 2022 (Version: 20220608AU)

New SM08502 in Colorectal cancer with APC Oncogenic mutations: 4

References: NCT05084859

New DS-6000a in Renal cell carcinoma, Ovarian cancer with CDH6 Protein expression: 4

NCT04707248. Phase 1 first-in-human evaluation of DS-6000a. 6 of 20 responder were seen across dosing levels. CDH is overexpressed in renal cell carcinoma and ovarian carcinoma. Cut-off to be determined. References: 10.1200/JCO.2022.40.16_suppl.3002

Changed Rucaparib in Ovarian cancer with BRCA1 Oncogenic mutations: 2

References changed: 3565848710.1200/JCO.22.01003.

Changed Nirogacestat in Adenoid cystic carcinoma with NOTCH1 R2327fs*: 3

References changed: 3499464410.1200/PO.21.00228.

Changed Adavosertib in Colorectal cancer with TP53+KRAS TP53:Oncogenic mutations AND KRAS:G12, TP53:Oncogenic mutations AND KRAS:G13: 3

References changed: 3453807210.1200/JCO.21.01435.

Changed Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with ARID1A Oncogenic mutations: 4

Comments changed: Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status..

Changed Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with ARID1B Oncogenic mutations: 4

Comments changed: Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status..

Changed Mirvetuximab soravtansine in Ovarian cancerOverexpression: 4

Biomarker changed: FOLR1.

Changed Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with PBRM1 Oncogenic mutations: 4

Comments changed: Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status..

Changed Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with SMARCA4 Oncogenic mutations: 4

Comments changed: Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status..

Changed Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with SMARCB1 Oncogenic mutations: 4

Comments changed: Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status..

Changed Carboplatin + Paclitaxel + Bevacizumab in Endometrial cancer, Uterine serous carcinoma with TP53 Overexpression, P151S, Y163C, R175H, L194R, Y220C, R248Q, R248W, R273C, R273H, R273L, R282W: 4

References changed: 3565847910.1200/JCO.21.02506.

Tuesday, 7 June 2022 (Version: 20220607AU)

New FOLFOX + Panitumumab in Colorectal cancer with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Panitumumab is TGA approved. Phase 3 PARADIGM trial (NCT02394795). In previously untreated KRAS wild-type metastatic colorectal cancer, Panitumumab significantly improved OS over bevacizumab in both left-sided tumour (37.9 v 34.3 months) and full analysis set populations (36.2 v 31.3 months). References: 10.1200/JCO.2022.40.17_suppl.LBA1

New Trabectedin in Ovarian cancer with BRCA1 Oncogenic mutations: R2

Phase 3. NCT02993705. MITO-203. In heavily pretreated platinum resistant ovarina cancer that harbour a BRCA mutation or has BRCA phenotypes, Trabectedin does not improve PFS (4.9 vs 4.4 months), OS, or objective response rate over standard chemotherapy (18% vs 22%). Exploratory analysis showed that OS was similar to non-platinum arm (median 15.8 v 16.0 months), inferior to carboplatin arm (median 22.0 months). References: 10.1200/JCO.2022.40.17_suppl.LBA5504

New Trabectedin in Ovarian cancer with BRCA2 Oncogenic mutations: R2

Phase 3. NCT02993705. MITO-203. In heavily pretreated platinum resistant ovarina cancer that harbour a BRCA mutation or has BRCA phenotypes, Trabectedin does not improve PFS (4.9 vs 4.4 months), OS, or objective response rate over standard chemotherapy (18% vs 22%). Exploratory analysis showed that OS was similar to non-platinum arm (median 15.8 v 16.0 months), inferior to carboplatin arm (median 22.0 months). References: 10.1200/JCO.2022.40.17_suppl.LBA5504

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 2

References changed: 3566578210.1056/NEJMoa2203690.

Monday, 6 June 2022 (Version: 20220606AU)

New Rucaparib in Ovarian cancer with BRCA1 Oncogenic mutations: 2

Phase 3. NCT03522246. ATHENA-MONO. In advanced epithelial ovarian cancer, In HRD population, PFS was significantly prolonged in Rucaparib arm over placebo (28.7 v 11.3 months). Note PFS was also significantly prolonged in ITT population (20.2 v 9.2 months). References: 10.1200/JCO.22.01003

New Rucaparib in Ovarian cancer with BRCA2 Oncogenic mutations: 2

Phase 3. NCT03522246. ATHENA-MONO. In advanced epithelial ovarian cancer, In HRD population, PFS was significantly prolonged in Rucaparib arm over placebo (28.7 v 11.3 months). Note PFS was also significantly prolonged in ITT population (20.2 v 9.2 months). References: 10.1200/JCO.22.01003

New Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 2

Not TGA approved. Phase 3. DESTINY-Breast04. NCT03734029. Compared with physician’s choice, T-DXD prolonged both PFS (10.1 v 5.4 months) and OS (23.9 v 17.5 months) in Hormone receptor-positive, HER2-low metastatic breast cancer. Similarly T-DXD also prolonged PFS (9.9 v 5.1 months) and OS (23.4 vs 16.8 months) compared to physician’s choice in the overall population. HER2-Low was defined as IHC a score of 1+ or 2+ with negative results on in situ hybridization. References: 10.1056/NEJMoa2203690

New Sacituzumab govitecan in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

NCT03901339. Phase 3. Tropics-02: In hormone receptor-positive, HER2-negative metastatic breast cancer, Sacituzumab govitecan significantly improved median PFS (5.5 vs 4.0 months) over treatment of physician choice. References: JCO.2022.40.17_suppl.LBA1001

New Rucaparib in Ovarian cancer with Homologous Recombination Deficiency Score High: 2

Phase 3. NCT03522246. ATHENA-MONO. In advanced epithelial ovarian cancer, In HRD population, PFS was significantly prolonged in Rucaparib arm over placebo (28.7 v 11.3 months). Note PFS was also significantly prolonged in ITT population (20.2 v 9.2 months). References: 10.1200/JCO.22.01003

New Adagrasib in Non-small cell lung cancer with KRAS G12C: 2

NCT03785249. In patients with previously treated metastatic non-small cell lung cancer, treatment with adagrasib resulted in ORR of 48/112 (43%), median PFS of 6.5 months and median OS of 12.6 months. References: 35658005

New Nimotuzumab + Gemcitabine in Pancreatic adenocarcinoma with KRAS NOT KRAS:oncogenic mutation: 2

Phase 3. NOTABLE. In previously untreated KRAS-wild type pancreatic cancer, addition of nimotuzumab to gemcitabine significantly improved survival over gemcitabine alone (10.9 vs. 8.5 months), one-year OS rate of 44% v 27%, and 3 year OS rate of 14% vs 3%. References: 10.1200/JCO.2022.40.17_suppl.LBA4011

New Fam-trastuzumab deruxtecan-nxki in Biliary tract cancer with ERBB2 Amplification, Overexpression: 3

JMA-IIA00423. ORR of 36% (8 of 22), DCR of 82%, median of PFS 4.4 months, and median OS of 7.1 months. References: 10.1200/JCO.2022.40.16_suppl.4006

New Patritumab deruxtecan in Breast cancer with ERBB3 Protein expression: 3

NCT02980341. In heavily pretreated metastatic breast cancer, Patritumab deruxtecan showed ORR of 30% in Hormone receptor-positive / HER2-negative MBC, 22% in metastic TNBC, and 43% in metastatic HER2-positive metatatic breast cancer. Median duration of response were 7.2, 5.9, and 8.3 months, respectively. References: 10.1200/JCO.2022.40.16_suppl.1002

New Navtemadlin in Merkel cell carcinoma with TP53 NOT Oncogenic mutations: 3

Phase 1/2. NCT03787602. Single-agent navtemadlin showed a confirmed ORR of 25% in metastatic Merkel cell carcinoma that was previously treated by PD-1 inhibition. References: 10.1200/JCO.2022.40.16_suppl.9506

New Fam-trastuzumab deruxtecan-nxki in Biliary tract cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 4

JMA-IIA00423. ORR of 12.5% (1 of 8) median of PFS 4.2 months, and ,edoam OS of 8.9 months. References: 10.1200/JCO.2022.40.16_suppl.4006

New Nimotuzumab + Gemcitabine in Pancreatic adenocarcinoma with KRAS NOT KRAS:oncogenic mutation: 4

NCT00561990. Phase 2. Exploratory analysis of PCS07 trial. In previously untreated, advanced pancreatic cancer, addition of nimotuzumab signficantly prolonged OS at 12 months compared to placebo (54% v 16%) in the KRAS wild type cohort. References: 28961832

New Capecitabine + Temozolomide in Pancreatic neuroendocrine tumour with MGMT Low protein expression, Methylation: 4

NCT01824875. E2211 trial. Higher odds of response to temozolomide was seen in MGMT Low protein expression (by IHC) or promoter methylation, with odds ratio of 6.4. References: 10.1200/JCO.2022.40.16_suppl.4004

Changed Futibatinib in Cholangiocarcinoma with FGFR2 Fusions: 3

Comments changed: NCT02052778. FOENIX-CCA2. Single-arm Phase 2 study. Intrahepatic cholangiocarcinoma. ORR 42% (43/103). DCR 83%. mPFS 8.9 months. Median OS 20.0 months.. References changed: 10.1200/JCO.2020.38.15_suppl.108, 10.1200/JCO.2022.40.16_suppl.4009.

Sunday, 5 June 2022 (Version: 20220605AU)

New Trastuzumab + Pertuzumab in Solid tumours with ERBB2 Amplification: 3

Phase 2. Basket. JRCT2031180150. N=40. ORR by BICR was 22.5%. References: 10.1200/JCO.2022.40.16_suppl.3131

New Entrectinib in Solid tumours with NTRK1 Fusion: 3

STARTRK-2. NCT02568267. N=150 with ORR of 61% (92/150). References: 10.1200/JCO.2022.40.16_suppl.3099

New Larotrectinib in Solid tumours with NTRK1 Fusion: 3

Pooled data from NCT02576431, NCT02122913, NCT02637687. N=269 with ORR of 69%. References: 10.1200/JCO.2022.40.16_suppl.3100

New Entrectinib in Solid tumours with NTRK2 Fusion: 3

STARTRK-2. NCT02568267. N=150 with ORR of 61% (92/150). References: 10.1200/JCO.2022.40.16_suppl.3099

New Larotrectinib in Solid tumours with NTRK2 Fusion: 3

Pooled data from NCT02576431, NCT02122913, NCT02637687. N=269 with ORR of 69%. References: 10.1200/JCO.2022.40.16_suppl.3100

New Entrectinib in Solid tumours with NTRK3 Fusion: 3

STARTRK-2. NCT02568267. N=150 with ORR of 61% (92/150). References: 10.1200/JCO.2022.40.16_suppl.3099

New Larotrectinib in Solid tumours with NTRK3 Fusion: 3

Pooled data from NCT02576431, NCT02122913, NCT02637687. N=269 with ORR of 69%. References: 10.1200/JCO.2022.40.16_suppl.3100

New Selpercatinib in Solid tumours with RET Fusion: 3

LIBRETTO-001. NCT03157128. ORR 44% (18/41) with median DOR was 24.5 months. References: 10.1200/JCO.2022.40.16_suppl.3094

New MIL93 in Solid tumours with CLDN18 Protein expression: 4

Phase 1. NCT04671875. In 10 evaluable patients, 1 responders were seen in CLDN18.2-positive gastric cancer achieved PR. References: 10.1200/JCO.2022.40.16_suppl.3086

New MORAb-202 in Solid tumours with FOLR1 Protein expression: 4

Phase 1. NCT03386942. Responses were seen in 10 of 22 across all dose levels. FR-alpha IHC was determined by any intensity in >= 5% of tumour cells. References: 33926914, 10.1200/JCO.2022.40.16_suppl.3090

New JAB-21822 in Non-small cell lung cancer, Colorectal cancer with KRAS G12C: 4

Phase 1. NCT05009329. References: 10.1200/JCO.2022.40.16_suppl.3089

New RMC-5552 + RMC-6272 in Non-small cell lung cancer with KRAS Oncogenic mutations: 4

Phase 1. NCT04774952. References: 10.1200/JCO.2022.40.16_suppl.3098

New ABN401 in Non-small cell lung cancer with MET Overexpression: 4

Phase 1. NCT04052971. Two responders were seen in tumour with MET overexpressed NSCLC. References: 10.1200/JCO.2022.40.16_suppl.3105

New ICP-723 in Solid tumours with NTRK1 Fusion: 4

Phase 1. NCT04685226. Four of 6 responders with NTRK fusion. References: 10.1200/JCO.2022.40.16_suppl.3106

New ICP-723 in Solid tumours with NTRK2 Fusion: 4

Phase 1. NCT04685226. Four of 6 responders with NTRK fusion. References: 10.1200/JCO.2022.40.16_suppl.3106

New ICP-723 in Solid tumours with NTRK3 Fusion: 4

Phase 1. NCT04685226. Four of 6 responders with NTRK fusion. References: 10.1200/JCO.2022.40.16_suppl.3106

New LY3143921 in Solid tumours with TP53 Oncogenic mutations: 4

Phase 1. NCT03096054. References: 10.1200/JCO.2022.40.16_suppl.3103

New Carboplatin + Paclitaxel + Bevacizumab in Endometrial cancer, Uterine serous carcinoma with TP53 Overexpression, P151S, Y163C, R175H, L194R, Y220C, R248Q, R248W, R273C, R273H, R273L, R282W: 4

Exploratory analysis of GOG-86P. NCT00977574. p53 IHC and/or TP53 gain-of-function mutations determines a subgroup of patient where addition of bevacizumab to chemotherapy in both PFS and OS. Overexpression was defined >= 80% of tumor cell nuclei showing intense staining by IHC. References: 10.1200/JCO.21.02506

New Niraparib in Solid tumours with BAP1 Oncogenic mutations: R2

Phase 2. NCT03207347. ORR was 1 of 18 responder (6%). References: 10.1200/JCO.2022.40.16_suppl.3122

Changed Mirvetuximab soravtansine in Ovarian cancerOverexpression: 3

Biomarker changed: FOLR1.

Changed Mirvetuximab soravtansine + Bevacizumab in Ovarian cancerProtein expression: 3

Biomarker changed: FOLR1.

Changed Cisplatin in Nonseminoma, Seminoma with Chromosome 3p25.3 copy number gain: R2

References changed: 35442716.

Friday, 3 June 2022 (Version: 20220603AU)

Monday, 30 May 2022 (Version: 20220530AU)

New Ivosidenib + Azacitidine in Acute myeloid leukaemia with IDH1 R132C, R132H, R132G, R132L, R132S: 2

FDA approved. Not TGA approved. Phase 3 AGILE. NCT03173248. In previously untreated IDH1 mutant AML, adding ivosidenib to azacitidine significantly prolonged both EFS and OS (median 24.0 vs 7.9 months). References: 35443108

New FOLFOXIRI + Bevacizumab + Atezolizumab in Colorectal cancer with Immunoscore IC High: 3

NCT03721653. Exploratory analysis from Phase 3 AtezoTRIBE. In experimental group, significant PFS benefit (HR:0.38) was seen in patients with high immunoscore IC treated with atezolizumab plus FOLFOXIRI and bevacizumab. Immunoscore IC digitally measures the densities and proximity of PD-L1 and CD8 cells on a single tissue section. References: 10.1016/S1470-2045(22)00274-1

New FOLFOXIRI + Bevacizumab + Atezolizumab in Colorectal cancer with Mismatch repair Deficient: 3

NCT03721653. Exploratory analysis from Phase 3 AtezoTRIBE. In experimental group, significant PFS benefit (HR:0.19) was seen in patients with mismatch repair reficiency treated with atezolizumab plus FOLFOXIRI and bevacizumab. References: 10.1016/S1470-2045(22)00274-1

New FOLFOXIRI + Bevacizumab + Atezolizumab in Colorectal cancer with Tumour Mutational Burden High: 3

NCT03721653. Exploratory analysis from Phase 3 AtezoTRIBE. In experimental group, significant PFS benefit (HR:0.23) was seen in patients with high TMB treated with atezolizumab plus FOLFOXIRI and bevacizumab. References: 10.1016/S1470-2045(22)00274-1

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with LRP1B Oncogenic mutations, deletions, Truncating mutations, Loss-of-function mutations: 4

Comments changed: Retrospective study. Significantly better outcomes with immune checkpoint inhibitors were seen in patients harboring pathogenic alteration of LRP1B gene, where longer PFS (HR 0.42) and OS (HR 0.62) were observed.. References changed: 33653800, 10.1200/JCO.2020.38.15_suppl.3007.

Wednesday, 25 May 2022 (Version: 20220525AU)

New Elacestrant in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2

Not TGA approved. Phase 3. EMERALD trial. In patients with ER-postive HER2-negative metastatic breast cancer treated with prior CDK4/6 inhibitor and up to 2 lines of endocrine therapy, SERD Elacestrant significantly improved PFS over standard-of-care endocrine therapy (6 month PFS rate: 34% vs 20%, 12 month PFS: 22 vs 9%). References: 35584336

New Elacestrant in Breast cancer with ESR1 Oncogenic mutations: 2

Not TGA approved. Phase 3. EMERALD trial. In patients with ER-postive HER2-negative metastatic breast cancer treated with prior CDK4/6 inhibitor and up to 2 lines of endocrine therapy also harbouring a ESR1 mutation, Elacestrant significantly improved PFS over standard-of-care endocrine therapy (6 month PFS rate: 41% vs 19%, 12 month PFS: 27 vs 8%). Stratification by ESR1 mutation is prespecified. References: 35584336

New Pembrolizumab, Nivolumab in Prostate cancer with CDK12 Oncogenic mutations, Loss-of-function mutations: 4

Retrospective study. In CDK12 altered metastatic castrate-resistance prostate cancer, 3 of 9 (ORR 33%) exposed to PD-1 inhibitors were associated with PSA response. Two of 9 had objective response to anti-PD-1 monotherapy. References: 32462107

New Olaparib, Rucaparib in Prostate cancer with CDK12 Oncogenic mutations, Loss-of-function mutations: R2

Retrospective study. In CDK12 altered metastatic castrate-resistance prostate cancer, no responses were seen in 11 patients receiving PARP inhibitors olaparib or rucaparib. Comutation profile was unknown. References: 32462107

New OP-1250 in Breast cancer with ESR1 Oncogenic mutations, Protein expression: 4

References: NCT04505826

Friday, 20 May 2022 (Version: 20220520AU)

New Trastuzumab, Ado-Trastuzumab Emtansine in Gastric cancer with ERBB2 MDK-ERBB2 fusion: 4

References: 25889497

New Trastuzumab, Ado-Trastuzumab Emtansine in Gastric cancer with ERBB2 ZNF207-ERBB2 fusion: R2

References: 25889497

Wednesday, 18 May 2022 (Version: 20220518AU)

New Atezolizumab + Tiragolumab in Non-small cell lung cancer with CD274 Protein expression: 3

Randomized phase 2 study. CITYSCAPE. NCT03563716. In chemotherapy naive, PD-L1-positive population, mMedian PFS was 5.4 months in tiragolumab plus atezolizumab versus 3.6 months in the atezolizumab group. ORR was 31% (tiragolumab + atezolizumab) v 16% (atezolizumab). PD-L1 positivity was defined as Tumour Proportion Score >= 1% using Dako 22C3 IHC pharma Dx assay. References: 10.1016/S1470-2045(22)00226-1

New Patritumab Deruxtecan in Prostate cancer with ERBB3 Overexpression: 4

Cell line and DX model studies. Antitumor activity was demonstrated in the in vitro HER3-positive prostate cancer cell lines, as well as activity against the HER3 high PDX model. References: 34753775

New Lapatinib in Solid tumours with ERBB3 P262H, G248R, Q809R: 4

References: 23680147

New Seribantumab in Breast cancer, Non-small cell lung cancer, Ovarian cancer, Solid tumours with NRG1 Fusion, DOC4-NRG1 fusion, SLC3A2-NRG1 fusion, CD74-NRG1 fusion: 4

Seribantumab inhibits in vitro and in vivo of NRG1 fusion in breast, lung, and ovarian patient-derived cancer models. References: 33824166

New Lumretuzumab in Lung squamous cell carcinoma with NRG1 High mRNA expression: 4

Exploratory analysis: ORR was 42.9% in the heregulin-high group with DCR was 100% (7/7 patients). ORR was 0% in the heregulin-low group. References: 31423336

New Patritumab in Prostate cancer with ERBB3 Overexpression: R2

Cell line and DX model studies. Lack of antitumor activity was demonstrated in vitro HER3-positive prostate cancer cell lines and PDX models through inhibition of HER3 alone. References: 34753775

New Pictilisib in Solid tumours with ERBB3 Q809R: R2

References: 23680147

New Ruxolitinib in Liquid cancers with JAK1 F958V, F958C, P960: R2

Cell line study. References: 21393331

New Ruxolitinib in Liquid cancers with JAK2 Y931C, Y931C and V617F: R2

Cell line study. References: 21393331

New Duligotuzumab + FOLFIRI in Colorectal cancer with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: R2

NCT01652482. Phase 2. In RAS wild-type metastatic colorectal cancer, there was no improvement of duligotuzumab plus FOLFIRI compared with cetuximab and FOLFIRI. References: 29506988

Changed Patritumab deruxtecan in Non-small cell lung cancer with EGFR Oncogenic mutations, Exon 20 insertions, Exon 19 deletions, G719, G724S, G719Y, T790M, C797S, L858R, L861Q: 3

References changed: 34548309, 10.1200/JCO.2021.39.15_suppl.9007.

Wednesday, 11 May 2022 (Version: 20220511AU)

New Trastuzumab + Lapatinib in Colorectal cancer with ERBB2 Amplification and S310F: 4

Case report. References: 34214965

Wednesday, 4 May 2022 (Version: 20220504AU)

New LY3537982 in Solid tumours with KRAS G12C: 4

References: 10.1158/1538-7445.AM2021-1259

New Cisplatin in Nonseminoma, Seminoma with Chromosome 3p25.3 copy number gain: R2

Cell line and retrospective observational studies. In laboratory cell line models and a multi-institutional cohort, copy number gain of chromosome cytoband 3p25.3 is associated with resistance to cisplatin. References:

Tuesday, 19 April 2022 (Version: 20220419AU)

New Veliparib in Triple-negative breast cancer with DAXX Overexpression: 4

Cell line study. Increased sensitivity to PARP1/2 inhibitor (veliparib) was observed in BRCA-Proficient triple-negative breast cancer cell-line with DAXX overexpression. References: 31029033

New Cetuximab, Panitumumab in Colorectal cancer with KRAS Amplification: R2

Cell line study. Tumors or cell lines harboring KRAS amplification are not responsive to anti-EGFR inhibitors. References: 23404247

New Cetuximab, Panitumumab in Colorectal cancer with KRAS Amplification: R2

Retrospective study. Multi-institutional cohort showing disease progression on treatment in 8 patients with KRAS amplified CRC receiving anti-EGFR therapies. References: 32376853

Wednesday, 13 April 2022 (Version: 20220413AU)

New Lapatinib, Afatinib, Ado-Trastuzumab Emtansine in Non-small cell lung cancer with ERBB2 V659E: 4

Retrospective case series. Response with prolonged PFS in one case harbouring V659E with both small molecule TKI and antibody drug conjugate. References: 10.1200/JCO.2020.38.15_suppl.e21521

New BMS-754807 in Colorectal cancer with IRS2 Amplification: 4

Cell lines with wild-type KRAS/BRAF were sensitive to BMS-754807 (in the presence of high IR-A RNA expression or low IGFBP6 levels). References: 25527633

New Ceritinib in Small-cell lung cancer with IRS2 Amplification, Protein expression: 4

Xenograft model study showing inhibition of cell growth by Ceritinib in IRS2-amplified/expressing PDX-derived cells. References: 32099898

New Linsitinib + Erlotinib in Non-small cell lung cancer with EGFR Oncogenic mutations: R2

Phase 2. Adding linsitinib to erlotinib resulted in inferior survival (8.4 versus 12.4 month). References: 27686971

New BMS-754807 in Colorectal cancer with IRS2+BRAF IRS2:Amplification AND BRAF:V600E: R2

Cell lines with BRAF V600E or KRAS G13D mutation were resistant to IGF1R inhibition BMS-754807. References: 25527633

New BMS-754807 in Colorectal cancer with IRS2+KRAS IRS2:Amplification AND KRAS:G13D: R2

Cell lines with BRAF V600E or KRAS G13D mutation were resistant to IGF1R inhibition by BMS-754807. References: 25527633

Tuesday, 12 April 2022 (Version: 20220412AU)

New Tucatinib + Ado-Trastuzumab Emtansine in Breast cancer with ERBB2 Amplification, Overexpression: 3

Phase 1b. NCT01983501. ORR was 47% with DOR of 6.9 months. References: 29955792

New Tucatinib + Trastuzumab in Breast cancer with ERBB2 Amplification, Overexpression: 4

Phase 1. NCT01921335. Dose escalation trial. Combination of trastuzumab and tucatinib was shown to be safe and have preliminary intracranial activities at both BD and daily dosing regimens, including subjects with prior exposure to neratinib and/or lapatinib. References: 32461105

New Tucatinib + Trastuzumab in Solid tumours with ERBB2 Amplification, Overexpression: 4

Preclinical study showing activity of tucatinib as single-agent or in combination of trastuzumab across PDX models of several cancer types. References: 32241871

New Tucatinib in Solid tumours with ERBB2 L755S, V777L, S310Y, G776delinsVC, G776delinsVG: 4

Tucatinib demonstrated activites in PDX models harbouring activating HER2 mutations. References: 10.1158/1538-7445.AM2020-4222

Changed Capecitabine + Trastuzumab + Tucatinib in Breast cancer with ERBB2 Amplification: 1B

References changed: 29804905, 31825569, 32468955, 34954044, 10.1200/JCO.2020.38.15_suppl.1005.

Saturday, 9 April 2022 (Version: 20220409AU)

New Atezolizumab + Vemurafenib + Cobimetinib in Melanoma with BRAF V600: 2

Not TGA approved. FDA approved. Phase 3 IMspire150. PFS is significantly prolonged versus control (15.1 vs 10.6 months) in the Atezolizumab arm. References: 32534646

New Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 2

Not TGA approved. NCT02855944. ARIEL4. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5·7 months), including both platinum sensitive and resistant populations. References: 35298906

New Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 2

Not TGA approved. NCT02855944. ARIEL4. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5·7 months), including both platinum sensitive and resistant populations. References: 35298906

New Pembrolizumab in Head and neck squamous cell carcinoma with CD274 Protein expression: 4

Phase 3. KEYNOTE-048. NCT02358031. Unplanned subgroup analysis showed HR 1.21 for OS (pembrolizumab vs cetuximab + chemotherapy) in the PD-L1 CPS < 1 group. HR was 0.71 (pembrolizumab vs cetuximab + chemotherapy) in CPS 1-19 group. In CPS >= 20 group, pembrolizumab was associated with higher OS 14.7 vs 11.0 months (HR 0.60). References: 35333599

New Cetuximab, ABT-806, Panitumumab, Gefitinib, Erlotinib in Gastric cancer, Gastroesophageal junction adenocarcinoma with EGFR Amplification: 4

Large international retrospective study (N=60). EGFR-amplified GEA received EGFRi, including 31 with concurrent chemotherapy. ORR was 43% and median PFS was 4.6 months across all lines. OS: 20.6 months (first-line), 9 months (second-line), and 8.4 months (third-line) exceeding historical real-world control of 11.2-month. References: 35349370

New Samuraciclib + Fulvestrant in Breast cancer with ESR1 Protein expression: 4

References: NCT03363893

New Cabozantinib + Nivolumab in Papillary renal cell carcinoma with FH Oncogenic mutations: 4

Phase 2. NCT03635892. Responses were seen in 10 of 12 patients with either NF2 or FH mutations. References: 35298296

New Cabozantinib + Nivolumab in Papillary renal cell carcinoma, Sarcomatoid renal cell carcinoma with NF2 Oncogenic mutations, Truncating mutations: 4

Phase 2. NCT03635892. Responses were seen in 10 of 12 patients with either NF2 or FH mutations. References: 35298296

New Selumetinib in High-grade gliomas with BRAF V600E: R2

NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR. References: 35363510

New Selinexor in Dedifferentiated liposarcoma with CALB1 High mRNA expression: R2

Phase 2/3. SEAL. NCT02606461. Exploratory RNAseq analysis showed lack of CALB1 expression was associated with longer median PFS with selinexor (6.9 months) compared with placebo (2.2 months). References: 35394800

New Selumetinib in Rhabdomyosarcoma, High-grade gliomas with KRAS Oncogenic mutations: R2

NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR. References: 35363510

New Selumetinib in High-grade gliomas with NF1 Oncogenic mutations: R2

NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR. References: 35363510

New Selumetinib in Rhabdomyosarcoma, Neuroblastoma with NRAS Oncogenic mutations: R2

NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR. References: 35363510

Changed Therapy in Solid tumours with HLA-A A*03: R2

Therapy changed: Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody, Avelumab, Nivolumab, Avelumab + AxitinibAnti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody, Avelumab, Nivolumab, Aveliumab + Axitinib.

Thursday, 7 April 2022 (Version: 20220407AU)

New Dabrafenib + Trametinib in Glioblastoma, High-grade glioma, Low-grade glioma with BRAF V600E: 2

Phase 2. ROAR. ORR was 33% (15/45) In high-grade glioma (10/31, 32% in glioblastoma). ORR was 69% (9/13) in the low-grade glioma cohort. References: 34838156

Changed Capecitabine + Trastuzumab + Tucatinib in Breast cancer with ERBB2 Amplification

Tier changed: 1B2. Comments changed: TGA approved; Not PBS reimbursed. FDA approved; HER2Climb: PFS: 7.8 (tucatinib) v 5.6 (placebo) months and OS 21.9 v 17.4 month. In the final OS analysis, median OS was also siginificantly longer (24.7 months in the tucatinib combination group) vs 19.2 months (placebo combination group).Not TGA approved; FDA approved; HER2Climb: PFS: 7.8 (tucatinib) v 5.6 (placebo) months and OS 21.9 v 17.4 month. In the final OS analysis, median OS was also siginificantly longer (24.7 months in the tucatinib combination group) vs 19.2 months (placebo combination group)..

Changed Vemurafenib with BRAF V600E: 2

Cancer type(s) changed: Erdheim-Chester disease, Langerhans Cell Histiocytosis Comments changed: Not TGA approved. Not PBS reimbursed. Secondary analysis of VE-BASKET study showed 62% confirmed ORR by RECIST and 100% PET response arte. PFS rate at 2 year was 86%.. References changed: 26287849, 29188284.

Wednesday, 6 April 2022 (Version: 20220406AU)

New Lapatinib + Trastuzumab in Breast cancer with ERBB2 D769Y, R896C: 4

References: 23220880

New Neratinib in Breast cancer with ERBB2 G309A, V777L, D769H, V842I, L755S, L755_759del: 4

References: 23220880

New MT-5111 in Breast cancer, Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Protein expression, Overexpression: 4

References: 10.1200/JCO.2020.38.4_suppl.433, 10.1158/1538-7445.SABCS19-P1-18-35

New Olaparib in Diffuse Intrinsic Pontine Glioma with PPM1D Loss-of-function mutations: 4

References: 32229503

New Afatinib in Colorectal cancer with KRAS Oncogenic mutations: R2

Randomised phase II trial. No activities is seen in Afatinib arm (ORR 0%, of 36) in KRAS mutant group. References: 25441408

Wednesday, 30 March 2022 (Version: 20220330AU)

New Olaparib in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 1B

TGA approved. POLO trial. References: 31157963

Changed Olaparib in Prostate cancer with CHEK2 Oncogenic mutations: 4

Comments changed: TOPARP-B; single case of PSA50 response but no RECIST response..

Saturday, 26 March 2022 (Version: 20220326AU)

New Vemurafenib in Anaplastic ganglioglioma, Anaplastic thyroid cancer, Cholangiocarcinoma, Biliary tract cancer, Erdheim-Chester disease, High-grade glioma, Langerhans cell histiocytosis, Low-grade glioma, Non-small cell lung cancer, Neuroendocrine carcinoma, Ovarian cancer, Salivary gland cancers, Sarcoma, Solid tumours except colorectal cancer, pancreatic adenocarcinoma with BRAF V600: 3

VE-BASKET. Phase 2. ORR of 33% (170) with median DOR 13 months. The selected cancer type has at least one responders. References: 32029534

New Pembrolizumab + Vibostolimab in Non-small cell lung cancer with CD274 Protein expression: 4

Phase 1. First-in-human MK7684-001. In treatment-naive NSCLC, combined anti-TIGIT and anti-PD-1 antibodies achieved DCR of 83% in TPS>=1% and in 45% in TPS<1%. DCR was 32% and 45% respectively in PD-L1/PD-L1 refractory subgroup. References: 34800678

New Vemurafenib in Pancreatic adenocarcinoma, Colorectal cancer with BRAF V600: R2

VE-BASKET. Phase 2. ORR in colorectal and pancreatic cancers were 0%. References: 32029534

Thursday, 24 March 2022 (Version: 20220324AU)

New Pembrolizumab in Endometrial cancer with Mismatch repair High: 2

Not TGA approved. FDA approved. Phase 2. NCT02628067. KEYNOTE-158, pooled analysis from Cohort D and K. N=79. ORR 48%. Median PFS: 13.1 months. Median DOR: not reached. Median OS: Not reached. References: 34990208

New Temozolomide + Ipilimumab + Nivolumab in Colorectal cancer with MGMT Loss of protein expression, Promoter methylation: 3

Phase II trial. MAYA. NCT03832621. In pre-treated, MGMT-silenced MSS colorectal cancer, sequencing temozolomide by priming followed by immune checkpoint blockade may induce durable clinical benefit. PFS at 8 months was 36%. Median PFS was 7.0 months. Medial OS was 18.4 months. References: 35258987

Changed Pembrolizumab in Endometrial cancer with Microsatellite Instability High

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. Phase 2. NCT02628067. KEYNOTE-158, pooled analysis from Cohort D and K. N=79. ORR 48%. Median PFS: 13.1 months. Median DOR: not reached. Median OS: Not reached..

Changed Therapy in Prostate cancer with PSMA Protein expression: 2

Therapy changed: Lu-177 vipivotide tetraxetanLutetium-177-PSMA-617. Comments changed: FDA approved 2022-03-24. Phase 3. VISION. N=831. PSMA-positive metastatic lesion defined as Gallium-68 positive. Median OS: 15.3 v 11.3 months (HR: 0.62). Radiological PFS: HR 0.40. 8.7 v 3.4 months..

Changed Therapy in Prostate cancer with PSMA Protein expression: 3

Therapy changed: Lu-177 vipivotide tetraxetanLutetium-177-PSMA-617.

Changed mRNA-5671 in Solid tumours with KRAS G12D, G12V, G13D, G12C

Tier changed: R24. Comments changed: Lack of efficacy. Trial closed. Updated 2022-03-23.

Monday, 21 March 2022 (Version: 20220321AU)

New Imatinib + Binimetinib in Gastrointestinal stromal tumour with KIT Exon 9 mutation, Exon 11 mutation, Exon 13 mutation: 3

Phase 2. NCT01991379. Combination of Imatinib and binimetinib was clinically active and produces deep and durable responses in treatment-naive GIST. Best ORR was 69% (29 of 42 evaluable patient has RECIST confirmed PR). 39 of 41 had Choi PR at 8 weeks. Median PFS was 29.9 months. Median OS was not reached. References: 35041493

New Olaparib in Breast cancer with BRCA1 Oncogenic mutations, S1253fs*10, 9435_9436delGT: 4

Case report. Durable response in a triple-negative breast cancer patient with somatic BRCA1 mutation and brain metastasis. References: 10.1200/PO.19.00012

New Everolimus in Perivascular epithelioid cell tumour with TSC1 Oncogenic mutations: 4

References: 23312829

New Everolimus in Perivascular epithelioid cell tumour with TSC2 Oncogenic mutations: 4

References: 23312829

New Sirolimus, Temsirolimus, Everolimus in Perivascular epithelioid cell tumour with TSC2 Oncogenic mutations: 4

Case series. Showing activity of mTOR inhibitors in extrarenal PEComas with TSC1/2 mutation or LOH. References: 22927055, 20048174, 20215136

New Imatinib + Binimetinib in Gastrointestinal stromal tumour with KIT V654A, N822K, N822Y, D820G: R2

References: 35041493

Changed Olaparib in Chondrosarcoma with IDH1 R132C, R132S, R132: 3

References changed: 3499464910.1200/PO.20.00247.

Tuesday, 15 March 2022 (Version: 20220315AU)

New Dabrafenib + Trametinib in Colorectal neuroendocrine carcinoma with BRAF V600E: 4

Two case reports of hHigh-grade rectal NEC with durable response to combined BRAF and MEK inhibition with DOR of 7 and 9 months respectively. References: 30181415

New ABBV-637 in Solid tumours with EGFR Amplification: 4

References: NCT04721015

New Trametinib in Melanoma with RAF1 FYCO1-RAF1 fusion: 4

Case report. Partial response for 40 weeks. References: 33684875

New Trametinib in Pilocytic astrocytoma with RAF1 NFIA-RAF1 fusion: 4

Case report. Best response at 6 months is stable disease. References: 27810072

New Trametinib in Spindle cell sarcoma with RAF1 QKI-RAF1 fusion: 4

Case report. Duration of response to trametinib 10 months with complete metabolic response on FDG-PET. References: 35050712

Changed Trametinib in Melanoma with RAF1 Fusion; ANO10-RAF1 fusion: 4

References changed: 3513509610.1200/PO.17.00138.

Changed Trametinib in Pancreatic acinar cell carcinoma with RAF1 Fusion; GATM-RAF1 fusion: R2

References changed: 3510073110.1200/PO.19.00159.

Saturday, 12 March 2022 (Version: 20220312AU)

New Olaparib in Breast cancer with PALB2 Oncogenic mutations (germline): 4

Case report. PALB2 c.18G>T with ARID1A Q1409*. Treatment with single-agent olaparib yielded DOR of 11 months. References: 32728620

Thursday, 10 March 2022 (Version: 20220310AU)

New Alectinib in Non-small cell lung cancer with ALK VKORC1L1-ALK fusion, T1151K: 4

Case report. References: 30519133

New Nivolumab in Malignant peripheral nerve sheath tumour with CD274 Amplification, protein expression: 4

Case report. PD-L1 > 90%. References: 10.1200/PO.18.00375

New Olaparib in Pancreatic adenocarcinoma with PALB2 Loss-of-function mutations (germline): 4

Phase 2 single arm study. NCT02677038 and NCT02511223. Single responder to olaparib (of two patients) with DOR 3.9 months. References: 33662100

New Crizotinib in Non-small cell lung cancer with ALK T1151K: R2

Case report. Secondary mutation for ALK resistance mutation. References: 30519133

New Olaparib in Pancreatic adenocarcinoma with ARID1A Loss-of-function mutations, Truncating mutations: R2

Phase 2 single arm study. NCT02677038 and NCT02511223. 0/ 3 responder in the DDR-GA cohort. References: 33662100

New Olaparib in Pancreatic adenocarcinoma with ATM Loss-of-function mutations, Truncating mutations, Loss-of-protein expression: R2

Phase 2 single arm study. NCT02677038 and NCT02511223. No objective response in 14 patients in both somatic and germline ATM alteration. No responders in 5 patients in the loss-of-protein expression group. References: 33662100

Changed Talazoparib in Non-small cell lung cancer with KEAP1 Oncogenic mutations: 4

References changed: 34963055.

Friday, 4 March 2022 (Version: 20220304AU)

New E-EDV-D682 in Pancreatic adenocarcinoma with EGFR Protein expression, Overexpression: 4

Interim data from Phase I/II ACTRN12619000385145. N=9. Confirmed response at 4 months in 4 of 5 patients. CBR 8 weeks 89%. References: 10.1200/JCO.2020.38.15_suppl.4632

New Talazoparib in Non-small cell lung cancer with KEAP1 Oncogenic mutations: 4

Preclinical study. Loss of KEAP1 induces a BRCAness phenotype in KEAP1-mutant lung cancer, mediated by stabilisation of EMSY, leading to sensitisation of PARP inhibitor. References:

New Itraconazole, Arsenic trioxide in Basal cell carcinoma, Medulloblastoma with PTCH1 Oncogenic mutations, Truncating mutations: 4

Preclinical study demonstrating in vitro activity of itraconazole. References: 23291299

New Itraconazole, Arsenic trioxide in Basal cell carcinoma, Medulloblastoma with SMO D477G, E522K, G457S, S391N, D388N, N223D, L225R: 4

Preclinical study. Itraconazole and arsenic trioxide block resistant SMO mutation activity in vitro. References: 23291299

New Vismodegib, Sonidegib in Basal cell carcinoma, Medulloblastoma with SMO D477G, E522K, G457S, S391N, D388N, N223D, L225R: 4

References: 23291299

Wednesday, 2 March 2022 (Version: 20220302AU)

Removed MET inhibitor in Solid tumours with MET alterations Alteration: Tier 4

Tuesday, 1 March 2022 (Version: 20220301AU)

New Ceralasertib + Adavosertib in Ovarian cancer, Endometrial cancer with CCNE1 Amplification: 4

Preclinical study. CCNE1 copy numbers predict the response to low-dose WEE1i-ATRi for CCNE-amplified ovarian and endometrial carcinomas. References: 34622231

Sunday, 27 February 2022 (Version: 20220227AU)

New Balstilimab + Zalifrelimab in Cervical cancer with CD274 Protein expression: 3

Phase 2. NCT03495882. ORR in PD-L1 positive subgroup 33% (22/67). ORR in PD-L1 negative subgroup was 9% (3/33). Overall DCR was 52%. The PD-L1 assay was measured by combined positive score >= 1% using 22C3 PharmDx assay. References: 34932394

New Poziotinib in Non-small cell lung cancer with ERBB2 Exon 20 insertion, A775_G776insYVMA, P780_Y781insGSP, G776delinsVC, V777_G778insV: 3

Phase 2. ZENITH20. N=90. In as-treated population across all lines of prior therapies, ORR was 28% (25/90), DCR was 70%, median was DOR 5.1 months and median was PFS 5.5 months. References: 34550757

New T-025 in Solid tumours with MYC Amplification: 4

Cell line study. CLK inhibitor showed stronger anti‐proliferative effects for cell lines of MYC‐amplified solid tumours than non‐amplified counterparts. References: 29769258

New Lapatinib in Glioblastoma with EGFR vIII: R2

References: 19499221

New Lapatinib in Glioblastoma with PTEN Loss of protein expression: R2

References: 19499221

Changed Trastuzumab + Pertuzumab + Docetaxel in Non-small cell lung cancer with ERBB2 Exon 20 insertion, Exon 20 mutation: 3

References changed: 35073148, 10.1200/JCO.2021.39.15_suppl.9015.

Wednesday, 23 February 2022 (Version: 20220223AU)

New Afatinib in Non-small cell lung cancer with EGFR G724S and R776H: 4

Case report. References: 33644199

New Osimertinib in Non-small cell lung cancer with EGFR R776H: 4

Retrospective study. References: 10.1200/JCO.2021.39.15_suppl.e21001

New Erlotinib, Gefitinib, Afatinib in Non-small cell lung cancer with EGFR R776H, L861Q, G719S and E709K, G719S and R776H, L747_T751del and D837T, L833V and H835L, L858R and G873E, L858R and A871E: 4

Retrospective study demonstrating response seen in harbouring the following mutations to first- and- second generation EGFR TKIs. References: 27875527

New JQ1 in Pancreatic adenocarcinoma with KDM6A Oncogenic mutations, Loss-of-function mutations: 4

Cell line study. KDM6A-deficient PDAC is sensitive to BET inhibitors and reversed squamous differentiation. References: 29533787

New Vorinostat, Trichostatin A, Valproic acid in Pancreatic adenocarcinoma with KDM6A Oncogenic mutations, Loss-of-function mutations: 4

Cell line study. Showing KDM6A sensitive cells are sensitive to HDAC inhibition. References: 30556125

Tuesday, 22 February 2022 (Version: 20220222AU)

New Nivolumab + Ipilimumab, Nivolumab + Fluorouracil + Cisplatin in Oesophageal squamous cell carcinoma with CD274 Protein expression: 2

Not TGA approved. FDA approved. Phase 3. CHECKMATE-648. NCT03143153. In PD-L1 positive population (>=1%), the addition of nivolumab to chemotherapy had significant longer median OS (15.4 months, Nivolumab + chemotherapy) vs. 9.1 months (chemotherapy alone). The combination of nivolumab + Ipilimumab was also significantly longer (median OS: 13.7 months). compared with the chemotherapy arm, PFS was significantly longer in chemoimmunotherapy arm (6.9 versus 4.4 months) in the PD-L1 positive population, but not in the nivolumab + ipilimumab arm. No OS difference in either Nivolumab arm from chemotherapy was seen in PD-L1 <1% group. PD-L1 status was primarily stratified by using tumour-cell PD-L1 expression (Dako IHC 28-8 pharmDx assay). References: 35108470

New Adagrasib in Non-small cell lung cancer with KRAS G12C: 3

Phase 1/1B. KRYSTAL-1. At 600mg BD, 10/16 evaluable NSCLC with KRAS G12C achieved objective response. References: 35167329

New Adagrasib in Solid tumours except non-small cell lung cancer with KRAS G12C: 4

Phase 1/1B. KRYSTAL-1. In a total of 7 cases (4 colorectal, 2 appendiceal, 1 duodenal adenocarcinomas) at various dosing levels, 1 (of 4) colorectal achieved an objective response. References: 35167329

Monday, 21 February 2022 (Version: 20220221AU)

New Abemaciclib in Mesothelioma with CDKN2A Loss of protein expression: 3

Phase 2. MiST2. NCT03654833. In p16ink4A-deficient, treatment with single-agent abemaciclib resulted in CBR of 14/26 (54%), with an ORR of 12% (3/26). Median PFS: 128 days. Median OS: 217 days. References: 35157829

New Pemigatinib in Solid tumours with FGFR2 Fusion, FGFR2-BICC1 fusion, FGFR2-CCDC6 fusion, FGFR2-CLIP1 fusion, FGFR2-USP33: 3

Phase 1. FIGHT-101. In FGFR fusion/rearragement cohort (N=20), ORR was 25% (5/20). References: 35176457

New Regorafenib + ABT-737 in Colorectal cancer with FBXW7 Oncogenic mutations: 4

Cell line study. Selective Mcl-1 inhibitors restore regorafenib sensitivty in CRC cell lines due to FBXW7-associated intrinsic or acquired resistance. References: 27399335

New Pemigatinib in Solid tumours with FGFR1 Amplification: 4

Phase 1. FIGHT-101. In the FGFR amplification group (N=26), a single responder was seen in FGFR1 amplification (ORR 3.8%). References: 35176457

New Pemigatinib in Solid tumours with FGFR1 N546K: 4

Phase 1. FIGHT-101. In the FGFR mutation subgroup, ORR was 23% (3/13). References: 35176457

New Pemigatinib in Solid tumours with FGFR2 Amplification: 4

Phase 1. FIGHT-101. In the FGFR amplification group (N=26), a single responder was seen in FGFR1 amplification (ORR 3.8%). References: 35176457

New Pemigatinib in Solid tumours with FGFR2 C382R: 4

Phase 1. FIGHT-101. In the FGFR mutation subgroup, ORR was 23% (3/13). References: 35176457

New Pemigatinib in Solid tumours with FGFR3 Amplification: 4

Phase 1. FIGHT-101. In the FGFR amplification group (N=26), a single responder was seen in FGFR1 amplification (ORR 3.8%). References: 35176457

New Pemigatinib in Solid tumours with FGFR3 S249C: 4

Phase 1. FIGHT-101. In the FGFR mutation subgroup, ORR was 23% (3/13). References: 35176457

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody, Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody, Anti-PD-L1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Urothelial carcinoma with CDKN2A Deletion, Loss-of-function mutations: R2

Retrospective analysis of 789 DFCI and 1250 MSKCC cohorts. CDKN2A genomic alterations were associated with reduced benefit from immune checkpoint blockades in urothelial carcinoma. However, results were inconsistent in gastroesophageal adenocarcinoma, head and neck squamous cell carcinoma, melanoma; non-small cell lung cancer, or renal cell carcinoma. References: 34074656

New Regorafenib in Colorectal cancer with FBXW7 Oncogenic mutations, S668fs*39, L403fs*34, R505C, R505H, R465C, R479Q, G579W, R658Q: R2

Cell line study. CRC cells with FBXW7 mutation has reduced Mcl-1 degradation and regorafenib resistance. References: 27399335

Thursday, 17 February 2022 (Version: 20220217AU)

New RO7428731 in Glioblastoma with EGFR vIII: 4

References: NCT05187624

New Erdafitinib in Non-small cell lung cancer with FGFR2 FGFR2-BICC1 fusion: 4

References: 35050756

Tuesday, 15 February 2022 (Version: 20220215AU)

New Sotorasib in Pancreatic adenocarcinoma with KRAS G12C: 3

Combined Phase 1 and 2 CodebreaK 100. NCT03600883. N=38. ORR was 21% (8/38) with DCR of 84% (32/38). Median PFS was 4.0 months with DOR 2.8 months. Median OS 6.9 months. References: 10.1200/JCO.2022.40.36_suppl.360490

New Dabrafenib in Pancreatic adenocarcinoma with BRAF N486_P490del: 4

Case report. DOR to dabrafenib was 6 months. References: 31519698

New Dabrafenib in Pancreatic adenocarcinoma with BRAF N486_P490del: 4

Cell line study. Demonstrating sensitivty of Dabrafenib in the delNVTAP cell line. References: 26996308

Thursday, 10 February 2022 (Version: 20220210AU)

New Copanlisib in Solid tumours with PIK3CA Oncogenic mutations, C420R, E453K, E542, E545, Q546, E726, H1047: 3

Phase 2. NCI-MATCH Z71F. N=25 in the primary efficacy analysis. ORR was 16% (4/25) versus 5% (null hypothesis). Median PFS 3.4 months. Median OS 5.9 months. CBR was 36%. No objective response was observed in the GI cancers. References: 35133871, 10.1200/JCO.2020.38.15_suppl.3506

Removed Copanlisib in Solid tumours with PIK3CA alterations Oncogenic mutations: Tier 4

Changed Niraparib in Prostate cancer with BRCA1 Oncogenic mutations (germline), Oncogenic mutations: 3

References changed: 3513104010.1016/S1470-2045(21)00757-9.

Changed Niraparib in Prostate cancer with BRCA2 Oncogenic mutations (germline), Oncogenic mutations: 3

References changed: 3513104010.1016/S1470-2045(21)00757-9.

Wednesday, 9 February 2022 (Version: 20220209AU)

New Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with ARID1A Oncogenic mutations: 4

Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status. References: 34375311

New Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with ARID1B Oncogenic mutations: 4

Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status. References: 34375311

New Trametinib in Pancreatic adenocarcinoma with BRAF Fusion; MBNL2-BRAF fusion; SND1-BRAF fusion; LUC7L2-BRAF fusion: 4

Case series. 3 (of 4) responders. References: 34476331

New Trametinib in Pancreatic adenocarcinoma with BRAF N486_P490del: 4

Case series. 1 (of 4 )responders. References: 34476331

New Trametinib, Ulixertinib in Pancreatic adenocarcinoma with BRAF N486_P490del: 4

Case report. DOR of trametinib was 5.5 months. CfDNA Response to Ulixertinib was shown. References: 34476331

New Vemurafenib + Cobimetinib in Pancreatic adenocarcinoma with BRAF T599_V600insT: 4

Case report. Duration of therapy was 20 week. References: 34476331

New Dabrafenib + Trametinib in Pancreatic adenocarcinoma with BRAF V600E: 4

Case series. N=2 Duration of therapy were 48 weeks and >2 years. References: 34476331

New Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with PBRM1 Oncogenic mutations: 4

Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status. References: 34375311

New Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with SMARCA4 Oncogenic mutations: 4

Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status. References: 34375311

New Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with SMARCB1 Oncogenic mutations: 4

Retrospective case series. In PDAC harbouring alterations in the SWI/SWF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status. References: 34375311

New Vemurafenib in Solid tumours with BRAF N486_P490del: R2

References: 26996308

Tuesday, 8 February 2022 (Version: 20220208AU)

New Niraparib in Prostate cancer with BRCA1 Oncogenic mutations (germline), Oncogenic mutations: 3

Phase 2. GALAHAD. NCT02854436. Objective response in the BRCA cohort (N=142) was 34%. References: 10.1016/S1470-2045(21)00757-9

New Niraparib in Prostate cancer with BRCA2 Oncogenic mutations (germline), Oncogenic mutations: 3

Phase 2. GALAHAD. NCT02854436. Objective response in the BRCA cohort (N=142) was 34%. References: 10.1016/S1470-2045(21)00757-9

New Pamiparib + Tislelizumab in Solid tumours with BRCA1 Oncogenic mutations: 4

Phase 1. NCT02660034. ORR 2 of 7 patients (29%) with BRCA1/2 mutation had partial response to the pamiparib and tislelizumab combination. NB in BRCA wild-type population, the overall response rate was 25% (6/24). References: 31378459

New Pamiparib + Tislelizumab in Solid tumours with BRCA2 Oncogenic mutations: 4

Phase 1. NCT02660034. ORR 2 of 7 patients (29%) with BRCA1/2 mutation had partial response to the pamiparib and tislelizumab combination. NB in BRCA wild-type population, the overall response rate was 25% (6/24). References: 31378459

New Pertuzumab + Trastuzumab in Breast cancer with ERBB2 G776V: 4

Case report. Concomitant PIK3CA (H1047R) and two MAP3K1 frameshift mutations. Duration of treatment on Nab-paclitaxel + Pertuzumab + Trastuzumab was 11 months. References: 10.1200/PO.16.00037

Changed Therapy in Colorectal cancer with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Therapy changed: Cetuximab, Panitumumab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI.

Changed Trastuzumab + Pertuzumab in Salivary gland cancers with ERBB2 : 3

Alterations changed: Amplification, Overexpression, L755F, D679H, G766V.

Changed Therapy in Colorectal cancer with BRAF V600E: R1

Therapy changed: Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI.

Friday, 4 February 2022 (Version: 20220204AU)

New RMC-4550 in Solid tumours with BRAF Class III mutations, G466V, G596R: 4

Cell line study demonstrating BRAF class III mutations are sensitive to SHP2 inhibition. References: 30104724

New RMC-4550 in Solid tumours with KRAS G12C: 4

Cell line study. References: 30104724

New RMC-4550 in Solid tumours with NF1 Oncogenic mutations, Loss-of-function mutations, N184fs, Q1336*: 4

Cell line study. References: 30104724

New RMC-4550 in Solid tumours with BRAF V600E, Class I mutations, Class II mutations, G469A: R2

Cell line study. References: 30104724

New RMC-4550 in Solid tumours with PTPN11 E76K: R2

Cell line study. References: 30104724

New RMC-4550 in Solid tumours with RAC1 P29S: R2

Cell line study. References: 30104724

New RMC-4550 in Solid tumours with RAF1 P261L: R2

Cell line study. References: 30104724

Changed Tepotinib in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation

Tier changed: 1B2. Comments changed: TGA approved. FDA approved. VISION trial. NCT02864992. N=152. Detection of MET exon14 skipping mutation was performed on either liquid biopsy or biospy of the archival tumour tissue. Across all lines of therapy in the efficacy population (N=99), ORR was 48% in the liquid-biopsy group and 50% in the tissue-biopsy group. Molecular cfDNA response to tepotinib was defined as complete response at least 75% of depletion of cfDNA.Not TGA approved. FDA approved. VISION trial. ORR 48%. All lines of therapy..

Changed Belvarafenib in Solid tumours with BRAF : 4

Alterations changed: Class III mutations, Class II mutations, Fusion.

Wednesday, 2 February 2022 (Version: 20220202AU)

New Pembrolizumab in Gastric cancer, Gastroesophageal junction adenocarcinoma with Microsatellite Instability High: 2

Not TGA approved. Post hoc analysis of MSI-H group in three Phase 3 RCTs. In single-agent pembrolizumab, the ORR were 57%, 47%, and 57% for KEYNOTE-059, 061, and 062 respectively. The corresponding estimated 12 months OS rate were 71%, 73%, and 79% respectively. Analysis by MSI status was prespecified. Note MSI-H is provisionally approved for solid tumour by the TGA. References: 33792646

New Palbociclib + Avelumab in Solid tumours with CCND1 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CCND2 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CCND3 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CDK4 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CDKN2A Oncogenic mutations, deletions, Truncating mutations, Loss-of-function mutations: 4

References: ACTRN12620000568910

New Olaparib in Mesothelioma with MRE11A L169Rfs*14, oncogenic mutations (germline): 4

Phase 2. NCT03531840. Olaparib has no activity in previously treated mesothelioma harbouring BAP1 mutations, except for a sole responder with germline MRE11A mutation. MRE11A is not in the inclusion criteria. References: 34661178

New Larotrectinib in Solid tumours with NTRK1 High mRNA expression: 4

References: ACTRN12619001147178

New Entrectinib in Pancreatic adenocarcinoma with NTRK1 TPR-NTRK1 fusion: 4

Two case reports. KRAS wild-type PDAC. One PR. References: 10.1200/PO.18.00039

New Larotrectinib in Solid tumours with NTRK2 High mRNA expression: 4

References: ACTRN12619001147178

New Larotrectinib in Solid tumours with NTRK3 High mRNA expression: 4

References: ACTRN12619001147178

New Entrectinib in Pancreatic adenocarcinoma with ROS1 SLC4A4-ROS1 fusion: 4

Case series. KRAS wild-type PDAC. Stable disease with duration of treatment of 7 months. References: 10.1200/PO.18.00039

New H3B-8800 in Myelodysplastic syndrome, Chronic myelomonocytic leukaemia, Acute myeloid leukaemia with SF3B1 Oncogenic mutations: 4

Phase 1. N=27. No CR or PR meeting IWG criteria but nine RBC transfusion free intervals were observed, including 5 of 15 transfusion-dependent MDS cases. References: 34172893

New H3B-8800 in Solid tumours, Liquid cancers with SF3B1 Oncogenic mutations: 4

References: 29457796

New H3B-8800 in Chronic myelomonocytic leukaemia with SRSF2 P95H: 4

References: 29457796

New Olaparib in Mesothelioma with BAP1 Oncogenic mutations, Loss-of-function mutations, Deletion: R2

Phase 2. NCT03531840. Olaparib has no activity in previously treated mesothelioma harbouring BAP1 mutations, except for a sole responder with concomitant germline MRE11A mutation. MRE11A is not in the inclusion criteria. References: 34661178

New Belvarafenib in Solid tumours with BRAF Class III mutations, Class II mutations: 4

TAPISTRY trial. References: NCT04589845

Changed GDC-0077 in Breast cancer with PIK3CA Oncogenic mutations: 4

Comments changed: Phase 1. NCT03006172. First-in-human ORR confirmed PR in 4 pts (20%). Clinical benefit rate was 45%; OncoKB LOE 3.

Sunday, 30 January 2022 (Version: 20220130AU)

New FOLFIRI + Cetuximab in Colorectal cancer with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

TGA approved. FDA approved. CRYSTAL. References: 19339720

Friday, 28 January 2022 (Version: 20220128AU)

New Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 2

Not TGA approved. FDA approved. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%. References: 34551229

New Tebentafusp in Melanoma, Uveal melanoma with HLA-A+PMEL HLA-A:A*02:01 and PMEL:Protein expression: 4

Phase 1. NCT01211262. OS rate at 12 months was 65% in both uveal melanoma and previously treated cutaneous melanoma. Gp100 is lineage-specific for melanocyte and melanoma cells. References: 32816891

New MRTX1133 in Solid tumours with KRAS G12D: 4

Discovery of the KRAS G12D inhibitor MRTX1133 showing reduction in volume in a pancreatic cancer xenograft mouse model. References: 34889605

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody, Avelumab, Nivolumab, Aveliumab + Axitinib in Solid tumours with HLA-A A*03: R2

HLA-A*03 was significantly associated with reduced OS after immune checkpoint inhibitor in the MSK-IMPACT and DFCI studies, JAVELIN solid tumour trials (HR 1.22-1.48), reduced PFS in nivolumab trials (CheckMate 009, 010, 025, HR1.31) and in JAVELIN renal 101 (HR 1.59 per allele) but not the control group. The meta-analysis showed that HLA-A*03 was associated with poor outcomes treated with ICI at genome-wide significance. References: 34895481

Tuesday, 25 January 2022 (Version: 20220125AU)

New Sorafenib in Gastrointestinal stromal tumour with KIT V560D, A502_Y503dup, V654A, T670I, D820A, D820E, D820G, D820Y, N822H, N822K, Y823D, A829P: 4

References: 22665524

New Imatinib in Gastrointestinal stromal tumour with PDGFRA D842V: 4

Cell line study. References: 15928335

New Sorafenib in Chronic eosinophilic leukaemia with PDGFRA FIP1L1-PDGFR fusion, T674I: 4

Cell line study. In transformed Ba/F3 cells, sorafenib inhibited cell growth in models that harbour FIPL1-PDGFRA and PDGFRA T674I. References: 16645167

New Sorafenib in Gastrointestinal stromal tumour with PDGFRA I843_D846del: 4

Case report. Durable response to Sorafenib (12.5 years) following progression on both Sunitinib and Nilotinib. References: 34949997

New Imatinib, Sorafenib, Sunitinib in Gastrointestinal stromal tumour with PDGFRA V561D, D842_H845del: 4

References: 22665524

New Imatinib in Gastrointestinal stromal tumour with PDGFRA V561D, N659K, D842Y, D842_I843delinsIM, D842_H845del, I843_H846del, Exon 18 deletion: 4

Cell line study. References: 15928335

New Sorafenib in Gastrointestinal stromal tumour with KIT D816H, D816V: R2

References: 22665524

New Imatinib, Sorafenib, Sunitinib in Gastrointestinal stromal tumour with PDGFRA D842V: R2

References: 22665524

New Imatinib, Nilotinib, Sorafenib in Chronic eosinophilic leukaemia with PDGFRA FIP1L1-PDGFRA fusion and T674I: R2

References: 21818111

Changed Encorafenib + Cetuximab in Colorectal cancer with BRAF V600E

Tier changed: 1B. Comments changed: PBS reimbursed. TGA approved. FDA approved. In Phase 3 BEACON CRC, OS for the encorafenib and cetuximab doublet was 8.2 months. The ORR was 26%.TGA approved. FDA approved. OS for E+C doublet 9.3 months. ORR 26.8%..

Changed Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Cisplatin + Paclitaxel, Pembrolizumab + Carboplatin + Paclitaxel in Cervical cancer with CD274 Protein expression: 2

Comments changed: Not TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (2021-10-13). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup.Not TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (13/10/2021). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup..

Changed Pembrolizumab + Cisplatin + Fluorouracil in Oesophageal cancer, Oesophageal Adenocarcinoma, Oesophageal squamous cell carcinoma with CD274 Protein expression: 2

Comments changed: Phase 3 KEYNOTE-590. FDA approved 2021-03-22. In the first-line setting, adding pembrolizumab to chemotherapy resulted in superior OS in PD-L1 positive subgroups (defined as CPS ≥ 10%, median 13.5 versus 9.4 mo), but also in ESCC and overall populations. Overall ORR in pembrolizumab arm was 45% (vs control 23%).Phase 3 KEYNOTE-590. FDA approved 22/03/2021. In the first-line setting, adding pembrolizumab to chemotherapy resulted in superior OS in PD-L1 positive subgroups (defined as CPS ≥ 10%, median 13.5 versus 9.4 mo), but also in ESCC and overall populations. Overall ORR in pembrolizumab arm was 45% (vs control 23%)..

Changed Amivantamab in Non-small cell lung cancer with EGFR Exon 20 insertion: 2

Comments changed: Not TGA approved. FDA accelerated approval 2021-05-21. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months.Not TGA approved. FDA accelerated approval 21/05/2021. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months..

Changed Mobocertinib in Non-small cell lung cancer with EGFR Exon 20 insertion: 2

Comments changed: Not TGA approved. FDA approved 2021-09-15. NCT02716116: Phase 1/2 trial. ORR to TAK-788 was 43% in 28 patients who had exon 20 insertion. Median DOR was 14 months. Median PFS was 7.3 months.Not TGA approved. FDA approved 15/09/2021. NCT02716116: Phase 1/2 trial. ORR to TAK-788 was 43% in 28 patients who had exon 20 insertion. Median DOR was 14 months. Median PFS was 7.3 months..

Changed Ivosidenib in Cholangiocarcinoma with IDH1 R132: 2

Comments changed: Not TGA approved. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months).Not TGA approved. FDA approved (25/08/2021). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months)..

Changed Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%.Not TGA approved. FDA approved 13/08/2021. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%..

Changed Imatinib in Sarcoma, Intimal sarcoma with PDGFRA Amplification: R2

Comments changed: Single-centre experience of case series in intimal sarcomas. No objective response to imatinib in 4 patients treated with PDGFR amplification.Single-centre experience of case series in intial sarcomas. No objective response to imatinib in 4 patients treated with PDGFR amplification..

Friday, 21 January 2022 (Version: 20220121AU)

New Repotrectinib in Solid tumours with ROS1 Fusion: 3

Phase 1. NCT03093116, ongoing clinical trial. Confirmed ORR 90% in 10 treatment-naive patients. In 18 pre-treated patients, the ORR was 28% with DOR of 10.2 months. Repotrectinib was shown to be active in patients with brain metastases. References: JCO.2019.37.15_suppl.9011

New Repotrectinib, Crizotinib in Neuroblastoma with ALK F1174V, F1174L, G1128A, I1171N, R1192P, F1245C, R1275Q, Y1278S: 4

Cell line study. Repotrectinib reduced the growth of ALK transfected PC12 cells that harbour constitutively active ALK mutations. References: 32269053

New Repotrectinib in Solid tumours with ALK Fusion, G1202R: 4

Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models. References: 30093503

New Repotrectinib in Solid tumours with NTRK1 Fusion, G595R: 4

Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models. References: 30093503

New Repotrectinib in Solid tumours with NTRK2 Fusion, G639R: 4

Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models. References: 30093503

New Repotrectinib in Solid tumours with NTRK3 Fusion, G623E, G623R: 4

Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models. References: 30093503

New Repotrectinib in Non-small cell lung cancer with ROS1 Fusion, CD74-ROS1 fusion, G2032R: 4

In both cell line and xenograft models, repotrectinib was active against preclinical models harbouring CD74-ROS1 fusion with or without G2032R subsitution. References: 32269053

New Repotrectinib in Solid tumours with ROS1 Fusion, G2032R, D2033N: 4

Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models. References: 30093503

Thursday, 20 January 2022 (Version: 20220120AU)

New Sunitinib in Paraganglioma, Phaeochromocytoma with RET Oncogenic mutations (germline): 3

Phase 2. SNIPP trial. N=25 enrolled. Overall DCR was 83%. Three patients with germline SDHB, SDHA, or RET mutations achieved RECIST objective response. References: 31105270

New Sunitinib in Paraganglioma, Phaeochromocytoma with SDHA Oncogenic mutations (germline): 3

Phase 2. SNIPP trial. N=25 enrolled. Overall DCR was 83%. Three patients with germline SDHB, SDHA, or RET mutations achieved RECIST objective response. References: 31105270

New Sunitinib in Paraganglioma, Phaeochromocytoma with SDHB Oncogenic mutations (germline): 3

Phase 2. SNIPP trial. N=25 enrolled. Overall DCR was 83%. Three patients with germline SDHB, SDHA, or RET mutations achieved RECIST objective response. References: 31105270

Wednesday, 19 January 2022 (Version: 20220119AU)

New Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations: 4

Phase 1. NCT02974738. The dose expansion cohort of this single-arm study with Belzutifan showed an ORR of 25% (14/55). DCR was 80% (44/55). Note VHL mutational status was not reported in this study, although VHL loss is common in RCC. References: 33888901

Tuesday, 18 January 2022 (Version: 20220118AU)

New Pembrolizumab in Endometrial cancer with Microsatellite Instability High: 3

Phase 2. NCT02628067. KEYNOTE-158, pooled analysis from Cohort D and K. N=79. ORR 48%. Median PFS: 13.1 months. Median DOR: not reached. Median OS: Not reached. References: 34990208

New Selumetinib + Irinotecan in Colorectal cancer with KRAS Oncogenic mutations: 4

Phase 2. 3 of 32 patient had partial response. The study was terminated before full accrual. References: 25322874

New AMG 337 in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with MET Amplification: 3

Phase 2. NCT02016534, Cohort 1. ORR was 18% (8/45). Eligibility criteria was MET/CEN-7 ratio ≥2.0 on FISH. References: 30366938

New Crizotinib in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with MET Amplification: 4

Case series. Two partial responders to crizotinib. References: 22042947

New Crizotinib in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with MET Amplification: 3

Phase 2. AcSé-Crizotinib. NCT02034981. In chemorefractory patients, the ORR to Crizotinib was 56% (5/9). Response after two cycles were 33%. PFS 3.2 months. MET amplification was determined by copy number >= 6 copies. References: 33847874

Changed Therapy in Colorectal cancer with KRAS Oncogenic mutations: 4

Therapy changed: Onvansertib + FOLFIRI + Bevacizumab, OnvansertibOnvansertib + FOLFIRI + Bevacizumab, Onvansertib.

Changed PLX4720 with RAF1 S257P, P261T, G356E, G361A, S427T, D447N, M469I, E478K, R554K: R2

Cancer type(s) changed: Solid tumours

Sunday, 16 January 2022 (Version: 20220116AU)

New Ravoxertinib in Solid tumours with BRAF Oncogenic mutations: 4

Phase 1. NCT01875705. N=47. Objective response seen in two BRAF-mutant colorectal cancers. Partial metabolic responses by FDG-PET were seen in 11 of 20 patients. References: 31848189

New SCH772984 in Solid tumours with BRAF Oncogenic mutations: 4

References: 23614898

New Birabresib in NUT carcinoma with BRD3 BRD3-NUTM1 fusion: 4

Phase 1. NCT02259114. 3/10 patients had partial response. Trial entry criteria was determined by ectopic expression of NUT protein or confirmed BRD-NUT translocation by FISH. References: 29733771

New Birabresib in NUT carcinoma with BRD4 BRD4-NUTM1 fusion: 4

Phase 1. NCT02259114. 3/10 patients had partial response. Trial entry criteria was determined by ectopic expression of NUT protein or confirmed BRD-NUT translocation by FISH. References: 29733771

New Birabresib in NUT carcinoma with BRD4 BRD4-NUTM1 fusion: 4

Case series from compassionate access. 2 of 4 patients had rapid response to Birabresib. References: 26976114

New Ravoxertinib in Solid tumours with KRAS Oncogenic mutations: 4

Phase 1. NCT01875705. N=47. Objective response seen in two BRAF-mutant colorectal cancers. Partial metabolic responses by FDG-PET were seen in 11 of 20 patients. References: 31848189

New SCH772984 in Solid tumours with KRAS Oncogenic mutations: 4

References: 23614898

New Crizotinib in Solid tumours with MET+KRAS MET:Amplification and KRAS:G12V: 4

Case report. Durable response over 19 months in a MET-amplified (16 copies, detected by next sequencing) carcinoma of unknown primary, with co-mutation of KRAS G12V. References: 25232318

New SCH772984 in Solid tumours with NRAS Oncogenic mutations: 4

References: 23614898

New Birabresib in NUT carcinoma with NUTM1 Protein expression: 4

Phase 1. NCT02259114. 3/10 patients had partial response. Trial entry criteria was determined by ectopic expression of NUT protein or confirmed BRD-NUT translocation by FISH. References: 29733771

New PLX4720 in with RAF1 S257P, P261T, G356E, G361A, S427T, D447N, M469I, E478K, R554K: R2

Cell line study. Random mutagenesis screen identified CRAF mutations confering resistance to RAF inhibitors. References: 23737487

Wednesday, 12 January 2022 (Version: 20220112AU)

New Crizotinib in Non-small cell lung cancer with MET Amplification: 3

Phase 2. N=38. ORR 38% for high (8/21, >=4 MET-to-CEP7 ratio on FISH), 14% for medium (2/14, >2.2 to <4 MET-to-CEP7 ratio), and 1 in 3 low (≥1.8 to ≤2.2 MET-to-CEP7 ratio). Median PFS were 6.7 months (high), 1.9 months (medium), and 1.8 months (low). References: 33676017

New Tepotinib in Non-small cell lung cancer with MET Amplification: 3

Phase II VISION Cohort B. N=24. MET gene copy number >=2.5 by liquid biopsy. No exon 14 skipping mutations. ORR 42%. In previously untreated patient, ORR 71%. References: 10.1200/JCO.2021.39.15_suppl.9021

New Crizotinib in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 3

Phase 2. NCT02499614. N=26. In previously treated NSCLC patients, the ORR was 27% (7/26). PFS 4.4 months. OS 5.4 months. MET amplification defined as MET/CEP7 ratio > 2.2. References: 31416808

New Crizotinib in Non-small cell lung cancer with ROS1 Fusion: 3

Phase 2. NCT02499614. Cohort A. N=26. In previously treated NSCLC patients, the ORR was 70% (17/26), including 1 CR. Median PFS 22.8 months. OS rate at 12 month 79%. ROS1 rearrangement defined by FISH in >= 15% of cells. References: 31416808

New Trametinib in Melanoma with NF1 Oncogenic mutations, Loss-of-function mutations: R2

Case report. Duration of response 5 months. References: 10.1200/PO.18.00028

New Selpercatinib in Non-small cell lung cancer with RET G810A, G810S, G810C, G810R: R2

Case report and xenograft studies. Acquired resistance after treatment with Selpercatinib as a result by steric hinderance of drug binding. References: 31988000

Changed Capmatinib in Non-small cell lung cancer with MET : 2

Alterations changed: Amplification, Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation. Comments changed: Not TGA approved; FDA approved; GEOMETRY mono-1: ORR 41% in 69 previously treated patients. Median DOR 9.7 months. ORR 68% in 28 treatment naive patients. Median DOR 12.6 months.Not TGA approved; FDA approved; GEOMETRY mono-1: In MET amplified group (defined as gene copy number, GCN, >= 10), ORR 29% (previously treated) versus 40% (previously untreated). Limited response were seen with GCN <10 (ORR 7-12%)..

Changed Therapy in Non-small cell lung cancer with MET Amplification: 3

Therapy changed: CapmatinibTepotinib. Comments changed: GEOMETRY mono-1: In MET amplified group (defined as gene copy number, GCN, >= 10), ORR 29% (previously treated) versus 40% (previously untreated). Limited response were seen with GCN <10 (ORR 7-12%).Phase II VISION Cohort B. N=24. MET gene copy number >=2.5 by liquid biopsy. No exon 14 skipping mutations. ORR 42%.. References changed: 32877583, 10.1200/JCO.2019.37.15_suppl.900410.1200/JCO.2021.39.15_suppl.9021.

Changed Crizotinib in Non-small cell lung cancer with MET Amplification, D1010, Exon 14 Deletion, Exon 14 splicing mutation, Y1003

Tier changed: 32.

Thursday, 6 January 2022 (Version: 20220106AU)

Wednesday, 5 January 2022 (Version: 20220105AU)

New Pexidartinib in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 2

FDA Approved. Phase 3. ENLIVEN. NCT02371369. ORR at week 25 Pexidartinib (39%) compared to placebo (0%). BOR was 53%. FDA approval 02/08/2019. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1. References: 31229240

New Emactuzumab in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 3

Phase 1. NCT01494688. Diffuse-type TGCT. N=28. ORR 84% (24/28) with two CR (7%) in combined dose escalation and expansion cohorts. Significant reduction in CD68/CD163-positive and CSF1R-positive macrophages was seen In 11 evaluable paired biopsy. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1. References: 26179200

New Nilotinib in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 3

N=56. 93% Patients who were progression-free at 12 weeks. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1. References: 29571946

New Pexidartinib in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 3

Phase 1. NCT01004861. N=23. Pexidartinib blocks the activity of CSF1R-dependent tumor-associated macrophage, required for tumour development. ORR was 52% (12/23) with partial response and DCR 83%. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1. References: 26222558

New Panitumumab + Fluorouracil in Colorectal cancer with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 3

Phase 2. PANAMA. N=248. In RAS-wildtype colorectal cancer following first-line induction therapy, maintenance therapy with 5-FU/Leucovorin plus panitumumab was significantly longer than 5-FU/Leucovorin alone (8.8 v 5.7 months, HR, 0.72). References: 34533973

New Imatinib in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 4

Case report. Complete response to Imatinib. References: 18296418

New Imatinib in Tenosynovial giant cell tumor with CSF1 Overexpression, Fusion, Rearrangement: 4

Retrospective study. ORR 19% (5/27) had RECIST-assessed responses, with 1 complete response and 4 partial responses. 20 (74%) had SD. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1. References: 21823110

New Gunagratinib in Solid tumours with FGFR2 Fusion: 4

Phase 1. ORR 33% in 12 patients including 1 CR (cholangiocarcinoma) and 3 PR. DCR 92%. References: 10.1200/JCO.2021.39.15_suppl.4092

New Gunagratinib in Solid tumours with FGFR2 N549H, V564I, K659N: 4

Cell line study. Ba/F3 cells harbouring both FGFR2-BICC1 fusion and secondary mutation remains sensitive to Gunagratinib. References: 10.1200/JCO.2021.39.15_suppl.4092

New PC14586 in Solid tumours with TP53 Y220C: 4

References: 10.1158/1538-7445.AM2021-LB006

New Pyrotinib in Non-small cell lung cancer with ERBB2 S335C: 4

Case report. Partial response to pyrotinib in the non-tyrosine kinase domain mutation S335C. References: 33655632

Changed Capecitabine + Trastuzumab + Tucatinib in Breast cancer with ERBB2 Amplification: 2

Comments changed: Not TGA approved; FDA approved; HER2Climb: PFS: 7.8 (tucatinib) v 5.6 (placebo) months and OS 21.9 v 17.4 month. In the final OS analysis, median OS was also siginificantly longer (24.7 months in the tucatinib combination group) vs 19.2 months (placebo combination group).. References changed: 31825569, 32468955, 34954044, 10.1200/JCO.2020.38.15_suppl.100531825569, 32468955, 10.1200/JCO.2020.38.15_suppl.1005.

Wednesday, 29 December 2021 (Version: 20211229AU)

New Tarloxotinib in Non-small cell lung cancer with ERBB2 Exon 20 insertion, A775_G776insYVMA: 3

Phase 2. RAIN-701 NCT03805841, Cohort B. 4/9 evaluable pts (44%) exhibited tumor reduction by RECIST and 2/9 pts experienced confirmed PR (22%). References: 10.1016/j.annonc.2020.08.2294

New Tarloxotinib in Non-small cell lung cancer with EGFR A763insFQEA, V769insASV, D770insSVD, H773insNPH: 4

Cell line study. References: 33710795

New Tarloxotinib in Non-small cell lung cancer with EGFR Exon 19 deletion and L718V, Exon 19 deletion and G724S, Exon 19 deletion and L792F, Exon 19 deletion and L792H, Exon 19 deletion and C797S, L858R and L718Q, L858R and L718V, L858R and L792F, L858R and L792H, L858R and C797G: 4

Cell line study. References: 33710795

New Afatinib in Non-small cell lung cancer with EGFR Exon 19 deletion and L718V, Exon 19 deletion and G724S, Exon 19 deletion and L792F, Exon 19 deletion and L792H, Exon 19 deletion and C797S, L858R and L718Q, L858R and L718V, L858R and L792F, L858R and L792H, L858R and C797G, L858R and C797S: 4

Cell line study. References: 33710795

New MVC-101 in Head and neck squamous cell carcinoma, Non-small cell lung cancer, Colorectal cancer with EGFR Protein expression: 4

References: NCT04844073

New Tarloxotinib in Solid tumours with ERBB2 Exon 20 insertion: 4

Cell line and xenograft study. Tarloxotinib-E showed activities in the inhibition of two models harboring EGFR exon 20 insertion mutations. References: 33355298

New Tarloxotinib in Solid tumours with ERBB2 Exon 20 insertion, A775_G776insYVMA: 4

Cell line and xenograft studies, and one case report. Tarloxotinib-E inhibits MDA-MB-175VIII cell line harboring HER2 exon 20 insertion or amplifications. Response in a clinical case report with ERBB2 A775_Y776insYVMA was seen. References: 33355298

New Tarloxotinib in Solid tumours with NRG1 DOC4-NRG1 fusion, CLU-NRG1 fusion: 4

Cell line and xenograft studies. Tarloxotinib-E inhibits MDA-MB-175VIII cell model harboring DOC4-NRG1 fusion, and a xenograft model harbouring CLU-NRG1 fusion. References: 33355298

New Afatinib, Poziotinib, Tarloxotinib in Non-small cell lung cancer with EGFR Exon 20 insertion and T790M and C797S: R2

Cell line study. References: 33710795

New Tarloxotinib in Non-small cell lung cancer with EGFR Exon 20 mutation: R2

Phase 2. RAIN-701 NCT03805841, Cohort B. ORR was 0% (N=11) for tumours with EGFR exon 20 mutations. References: 10.1016/j.annonc.2020.08.2294

New Tarloxotinib in Non-small cell lung cancer with EGFR H773insH: R2

Cell line study. References: 33710795

New Tarloxotinib in Non-small cell lung cancer with EGFR L858R and C797S: R2

Cell line study. References: 33710795

New Tarloxotinib, Afatinib, Poziotinib, Osimertinib, Pyrotinib in Non-small cell lung cancer with ERBB2 C805S: R2

Cell line mutagenesis study identified C805S arising in Ba/F3 cells after treatment with Tarloxotinib and other TKIs. C805S is a secondary mutation, homologous to EGFR C797, that interfere with covalent bonding from the irreversible TKIs. References: 34584864

New Tarloxotinib in Non-small cell lung cancer with ERBB3 Amplification, Overexpression: R2

Cell line study. ER3 overexpression was identified as a mechanism of resistance to tarloxotinib-E. References: 34584864

New Entinostat + Exemestane in Breast cancer with ESR1 Protein expression: R2

Phase 3 E2112 trial. NCT02115282. N=608. Entinostat did not improve PFS over placebo (3.3 versus 3.1 months) or OS (23.4 vs 21.7 months) in combination with exemestane. ORR was 6% (Placebo 6%). 35% in the received CDK4/6 prior inhibitor, and 31% received fulvestrant. The Phase 3 data thus contrasts earlier Phase 2 data where a significance improvement of PFS was observed (median PFS 4.3 months versus 2.3 months). References: 34357781, 23650416

Changed Dabrafenib + Trametinib with BRAF V600E: 3

Cancer type(s) changed: Gliomas, High-grade gliomas, Low-grade gliomasGlioma, High-grade glioma, Low-grade glioma

Changed Trastuzumab + Pertuzumab with ERBB2 Amplification; Overexpression: 3

Cancer type(s) changed: Biliary tract cancers, Cholangiocarcinoma, Gallbladder cancer, Ampullary carcinomaBiliary tract cancers, Cholangiocaricnoma, Gallbladder cancer, Ampullary carcinoma

Changed Crizotinib with MET Exon 14 skipping mutation, c.2888-5_2944del: 4

Cancer type(s) changed: Histiocytic sarcomaHistocytic sarcoma

Changed Trametinib with CAMTA1 TAZ-CAMTA1 fusion: R2

Cancer type(s) changed: Epithelioid haemangioendotheliomaEpithelioid hemangioendothelioma

Tuesday, 21 December 2021 (Version: 20211221AU)

New Pamiparib in Ovarian cancer with BRCA1 Oncogenic mutations (germline): 2

Phase 2. NCT03333915. In Chinese patients with advanced ovarian cancer that harbour BRCA mutations, pamiparib achieved ORR of 65% in platinum-sensitive disease (cohort 1, 53/82, including 8 CR) and 32% (cohort 2, 6/19) in platinum-resistant disease. PFS were 15.2 (cohort 1) months and 6.2 (cohort 2) months respectively. Approved in China April 2021. References: 10.1016/j.annonc.2020.08.959, 34844979

New Pamiparib in Ovarian cancer with BRCA2 Oncogenic mutations (germline): 2

Phase 2. NCT03333915. In Chinese patients with advanced ovarian cancer that harbour BRCA mutations, pamiparib achieved ORR of 65% in platinum-sensitive disease (cohort 1, 53/82) and 32% (cohort 2, 6/19) in platinum-resistant disease. PFS were 15.2 (cohort 1) months and 6.2 (cohort 2) months respectively. Approved in China April 2021. References: 10.1016/j.annonc.2020.08.959, 34844979

New Imatinib in Gastrointestinal stromal tumour with NF1+KIT NF1:Oncogenic mutations AND NOT KIT:Oncogenic mutations: R2

In a case series of NF1-associated GIST treated with imatinib, primary resistance was shown in three patients. References: 18628470

Changed Pyrotinib + Irinotecan in Gastric cancer with ERBB3 V104L: 4

References changed: 33500629.

Changed Capivasertib + Paclitaxel in Breast cancer with ESR1+PIK3CA ESR1:protein expression and PIK3CA:oncogenic mutation: R2

References changed: 30860570.

Monday, 20 December 2021 (Version: 20211220AU)

New Nirogacestat in Aggressive fibromatosis with APC Loss-of-function mutations; oncogenic mutations: 3

N=17. A total of 15 patients had APC or CTNNB1 mutations. ORR was 29% (5/17), and 5/17 had stable disease. Neither APC loss-of-function or CTNNB1 gain-of-function mutations was selected prospectively, but are known central alteration in aggressive fibromatosis. Responses were seen regardless of APC or CTNNB1 mutations. References: 28350521

New Nirogacestat in Aggressive fibromatosis with CTNNB1 T41A, S45F, Gain-of-function mutations: 3

N=17. A total of 15 patients had APC or CTNNB1 mutations. ORR was 29% (5/17), and 5/17 had stable disease. Neither APC loss-of-function or CTNNB1 gain-of-function mutations was selected prospectively, but are known central alteration in aggressive fibromatosis. Responses were seen regardless of APC or CTNNB1 mutations. References: 28350521

Removed PF-03084014; Gamma secretase inhibitor in Aggressive fibromatosis with APC alterations Loss-of-function mutations: Tier 4

Removed PF-03084014; Gamma secretase inhibitor in Aggressive fibromatosis with CTNNB1 alterations Gain-of-function mutations: Tier 4

Friday, 17 December 2021 (Version: 20211217AU)

New Zorifertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 3

References: 29056570

New Lucitanib in Breast cancer with FGFR1 Amplification: 3

Phase 2. FINESSE. NCT02053636. In HR+/HER2− metastatic breast cancer, ORR was 19% in the FGFR1-amplified cohort (defined as gene/centromere ratio ≥2 or average copy number ≥6). References: 31619444

New GSK2849330 in Solid tumours with ERBB3 Protein expression: 4

Phase 1. NCT01966445. Escalation and expansion cohort. HER3 positivity is defined by IHC. N=29. No responders apart from 1 PR which harbours NRG1 fusion, 7 SD, 16 PD. References: 34132450

New Sorafenib in Thymic carcinoma with KIT D820E: 4

Case report. PR 15 months. References: 19461405

New Sorafenib in Thymic carcinoma with KIT P577_Y579del: 4

Case report. SD for at least 6 months with metabolic response on FDG-PET. References: 20970876

New Imatinib in Thymic carcinoma with KIT Y553N: 4

Case report. PR 8 months. References: 21969494

New GSK2849330 in Non-small cell lung cancer with NRG1 CD74-NRG1 fusion: 4

Phase 1. NCT01966445. Single responder with durable response. References: 34132450

New Tazemetostat in Ovarian small cell carcinoma with SMARCA2+SMARCA4 SMARCA2:Loss of protein expression and SMARCA4:Loss of protein expression: 4

References: 28292935

New Tazemetostat in Ovarian small cell carcinoma with SMARCA4 Loss of protein expression: 4

References: 26356327

New LY3023414 in Endometrial cancer with AKT1 Oncogenic mutations: R2

N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months. References: 31880826

New Sotorasib in Colorectal cancer with KRAS G12C: R2

Phase 2. CodeBreaK 100. N=62. In heavily previously treated colorectal cancer, single-agent Sotorasib yielded an ORR of 9.7% (6/62, all PR) with lower bound 95% CI not exceeding prespecified benchmark. Median DOR 4.2 months. Median OS 10 months. DCR 51/62 (82.3%). References: 10.1016/S1470-2045(21)00605-7

New LY3023414 in Endometrial cancer with PIK3CA Oncogenic mutations: R2

N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months. References: 31880826

New LY3023414 in Endometrial cancer with PIK3R1 Oncogenic mutations: R2

N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months. References: 31880826

New LY3023414 in Endometrial cancer with PTEN Loss-of-function mutations: R2

N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months. References: 31880826

New Cisplatin in Solid tumours with SMARCA4 Oncogenic mutations: R2

SMARCA4/2 loss reduces apoptosis induced by chemotherapy through disrupting intracellular organelle calcium ion release via IP3R3-mediated mechanism. References: 34518526

Thursday, 16 December 2021 (Version: 20211216AU)

New Crizotinib in Non-small cell lung cancer with ROS1 EZR-ROS1 fusion: 4

Case report. Crizotinib resulted in a 6-month clinical benefit in a NSCLC patient harbouring EZR-ROS1 fusion. References: 29361925

New Entrectinib in Papillary thyroid cancer with ROS1 EZR-ROS1 fusion: 4

References: 32913977

New RLY-4008 in Solid tumours with FGFR2 Fusion: 4

References: 10.1200/JCO.2021.39.15_suppl.TPS4165

Changed Anti-PD-1 monoclonal antibody, immune checkpoint blockade,PD-L1 targeting in Solid tumours with CD274 Amplification: 4

Comments changed: Should validate by IHC, retrospective review suggest ORR 66%.

Friday, 10 December 2021 (Version: 20211210AU)

New Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Promoter methylation: 4

Retrospective analysis of Part 1 of ARIEL2 trial: homozygous or hemizygous BRCA1 methylation is associated with response to rucaparib in BRCA1-methylated platinum-sensitive recurrent high-grade serous ovarian cancer. In BRCA1-methylated PDX models, silencing of BRCA1 copies predicts rucaparib response. References: 30266954

Tuesday, 7 December 2021 (Version: 20211207AU)

New Dabrafenib + Trametinib in Glioma, High-grade glioma, Low-grade glioma with BRAF V600E: 3

Phase 2. NCT02034110. In high-grade gliomas: ORR 33% (15/45), including 3 CR. Median PFS 3.8 months. Median OS 17.6 months. In low-grade gliomas: ORR 69% (9/13), including 1 CR. Median PFS and OS not reached. References: 34838156

Monday, 6 December 2021 (Version: 20211206AU)

New Afatinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

References: 31567148

New Erlotinib, Osimertinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

Case report showing response to both erlotinib and osimertinib (4 and 15 months respectively) in a patient with carcinomatous meningitis. Duplication of intron 17-25 was detected by Sanger sequencing. References: 34240806

New Gefitinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

Case report of tandem duplication of exons 18-25 responding to Gefitinib with durable response. References: 26398831

New Icotinib, Osimertinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

Case report. Response to Icotinib and second line osimertinib. Duration of response 21 months. References: 33392076

New Osimertinib in Non-small cell lung cancer with EGFR Kinase domain duplication: 4

References: 34261918

New Osimertinib, Lazertinib in Non-small cell lung cancer with EGFR Kinase domain duplication AND T790M: 4

Cell line study. EGFR-KDDT790M Ba/F3 cell line. T790M-positive cell lines were sensitive to 3rd generation TKIs. References: 33940786

New RXC004 in Colorectal cancer with RNF43 Oncogenic mutations: 4

Phase 1. EudraCT 2017-000720-98. 2 cases of SD in Wnt ligand dependent group (RNF43 mutation or RSPO1 fusion). References: 10.1016/j.annonc.2021.08.1039

New RXC004 in Colorectal cancer with RSPO1 Fusion: 4

Phase 1. EudraCT 2017-000720-98. 2 cases of SD in Wnt ligand dependent group (RNF43 mutation or RSPO1 fusion). References: 10.1016/j.annonc.2021.08.1039

New Gefitinib, Erlotinib, Afatinib, Dacomitinib in Non-small cell lung cancer with EGFR Kinase domain duplication AND T790M: R2

Cell line study. EGFR-KDDT790M Ba/F3 cell line. T790M-positive Ba/F3 cell lines were resistant to 1st and 2nd generation EGFR TKIs. References: 33940786

New Osimertinib, Lazertinib in Non-small cell lung cancer with EGFR Kinase domain duplication AND T790M AND C797S: R2

Cell line study. EGFR-KDDT790M Ba/F3 cell line. C797S in kinase domain 2 was found mediating resistance mechanism against 3rd generation EGFR TKIs. References: 33940786

Thursday, 2 December 2021 (Version: 20211202AU)

New Belzutifan in Pancreatic neuroendocrine tumour, Hemangioblastoma with VHL Oncogenic mutations (germline): 3

MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas. References: 34818478, 10.1200/JCO.2021.39.15_suppl.4555

New Neratinib in Breast cancer with ERBB2 V777L, D769H, V842I, L755S, R678Q, G309A: 4

Cell line and xenograft studies showing sensitivity to neratinib in selected ERBB2 kinase domain, juxtamembrane, and extracellular domain mutations. References: 23220880

New Belzutifan in Paraganglioma, Somatostatinoma, Polycythemia vera with EPAS1 A530E (germline); Oncogenic mutations (germline): 4

Case report of Pacak-Zhuang syndrome. Treatment with belzutifan led to a rapid and sustained tumour and biochemical response with resolution of polycythemia. References: 34818480

Changed Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. FDA approved 13/08/2021. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%.Not TGA approved. FDA approved 13/08/2021. Study 004. N=61. ORR 36% (22/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%. ORR 80% (16/20) for PNET and 32% (16/50) CNS hemangioblastomas.. References changed: 34818478, 10.1200/JCO.2021.39.15_suppl.4555.

Friday, 26 November 2021 (Version: 20211126AU)

New Trastuzumab + Pertuzumab in Colorectal cancer with ERBB2 ERBB2:amplification: 3

Phase 2. TRUMPH. HER2 amplified and RAS wildtype colorectal cancer. ORR 28% ctDNA-positive group (PFS 3.1 months) and 30% in tissue-positive group (PFS 4.0 months). References: 34764486

Thursday, 25 November 2021 (Version: 20211125AU)

New MGC018 in Prostate cancer with CD276 Protein expression: 4

NCT03729596. Phase 1 expansion cohort studying MGC018 in B7-H3-expressing tumors. One partial radiological response observed, and 11 of 22 PSA response was seen in metastatic castrate-resistant prostate cancers. References: 10.1016/j.annonc.2021.08.1133

New MGC018 in Solid tumours with CD276 Protein expression: 4

NCT03729596. Phase 1 dose escalation study of MGC018. References: 10.1200/JCO.2021.39.15_suppl.2631

Wednesday, 24 November 2021 (Version: 20211124AU)

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody, Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Solid tumours with EPHA7 Oncogenic mutations: 4

Retrospective study showing EPHA7 mutant cancers have better clinical outcomes(higher ORR 53% vs 29% wild type, and duration of clinical benefit, 70 vs 43%) in cancer patients treated with immune checkpoint inhibitors. References: 33526018

Changed Ensartinib in Non-small cell lung cancer with ALK Fusion: 2

References changed: 3447319410.1001/jamaoncol.2021.3523.

Changed Nab-sirolimus in Perivascular epithelioid cell tumour with TSC2 Loss-of-function mutations

Tier changed: 23. Comments changed: FDA approved. Phase 2 AMPECT. ORR was 89% (8/9) in TSC2 mutant group. ORR was 2/16 (13%) in the non-TSC2 mutant group.Phase 2 AMPECT. ORR 89% (8/9) in TSC2 mutant group. ORR 2/16 (13%) in the non-TSC2 mutant group..

Monday, 22 November 2021 (Version: 20211122AU)

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with POLD1 Oncogenic mutations: 4

Retrospective variant registry analysis showing POLE/POLD1 mutants have higher ORR (35%) versus wildtype (20%) when treated with immune checkpoint blockades. References: 33569431

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with POLE Oncogenic mutations: 4

Retrospective variant registry analysis showing POLE/POLD1 mutants have higher ORR (35%) versus wildtype (20%) when treated with immune checkpoint blockades. References: 33569431

New Vemurafenib in Melanoma with BRAF K601E: R2

Case report. Lack of response to melanoma. References: 31182949

Changed LY3009120 in Solid tumours with BRAF : 4

Alterations changed: A400V, G464V, G466V, G464E, L485_P490del, N581S, L597R, K601N, G469A, N581Y, G569RA400V, G464V, G466V, G464E, N581S, L597R, K601N, G469A, N581Y, G569R.

Monday, 15 November 2021 (Version: 20211115AU)

New Sotorasib in Non-small cell lung cancer with BRAF G569R: R2

Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models. References: 34759319

New Sotorasib in Non-small cell lung cancer with KRAS G12V: R2

Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models. References: 34759319

New Sotorasib in Non-small cell lung cancer with MRAS Q71R: R2

Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models. References: 34759319

New Sotorasib in Non-small cell lung cancer with NRAS Q61K, G13R: R2

Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models. References: 34759319

Changed Mobocertinib in Non-small cell lung cancer with EGFR Exon 20 insertion, A763_Y764insFQEA, V769_D770insGG, V769_D770insASV, D770_N771insG, D770_N771insGL, D770_N771insGD, D770delinsGY, N771delinsKH, N771_P772insH, P772_H773insPNP, H773_V774insNPH, V774_C775insHV: 3

Comments changed: NCT02716116. Combined PPP and EXCLAIM cohort..

Thursday, 11 November 2021 (Version: 20211111AU)

New Afatinib, Osimertinib in Non-small cell lung cancer with EGFR T751_I759delinsS: 4

Case report. References: 34729927

New Trametinib in Histiocytosis with MAP2K1 L98_K104delinsQ: R2

References: 29768711

Changed Therapy in Breast cancer with PIK3CA : 4

Therapy changed: Taselisib, Alpelisib, Inavolisib. Alterations changed: E542K and E453, E542K and E726K, E542K and M1043, E545K and E453, E545K and E726, E542K and M1043, H1047R and E453, H1047R and E726K, E543Q and H1047R, E726K and H1047R. Comments changed: Double PIK3CA mutations in cis increased sensitivity to PI3K alpha inhibitors..

Wednesday, 10 November 2021 (Version: 20211110AU)

New Ceralasertib in Solid tumours with ARID1A Oncogenic mutations AND Loss of protein expression: 3

Phase 2. Interim result from NCT03682289. N=10 in the ARID1A-deficient cohort (defined as negative IHC staining for BAF250a). ORR 20% (2/10) with both responders being CR. One patient with prolonged SD (8.8 month). Accrual is ongoing. References: 10.1016/j.annonc.2021.08.1034

New Vemurafenib in Non-small cell lung cancer with BRAF V600E, V600K, V600M: 3

Phase 2. AcSé. NCT02304809. ORR: 43 of 96 (45%) patients. Median PFS 5.2 months. Median OS 10 months. References: 31959346

New Pyrotinib + Irinotecan in Gastric cancer with ERBB3 V104L: 4

References:

New Ceralasertib + Olaparib in Solid tumours with ARID1A Oncogenic mutations AND NOT Loss of protein expression: R2

Phase 2. Interim result from NCT03682289. N=10 in the ARID1A-intact cohort (defined as positive IHC staining for BAF250a). ORR 0% (0/10) with best response of SD in 4/10 patients. References: 10.1016/j.annonc.2021.08.1034

New Vemurafenib in Non-small cell lung cancer with BRAF Oncogenic mutations AND NOT V600: R2

Phase 2. AcSé. NCT02304809. ORR: 0%. References: 31959346

Changed Lapatinib + Trastuzumab in Breast cancer with ERBB3 G284R: 4

Comments changed: Case report. Third-line therapy in HER2-negative breast cancer led to complete metabolic response and radiological partial response..

Changed Afatinib in Urothelial carcinoma with ERBB3 G284R, V104M, R103G: 4

Comments changed: Phase 2. Platinum-Refractory metastatic urothelial carcinoma. Pre-defined patient selection based on ERBB aberrations. While overall the trial did not meet the primary point of PFS3, three patients with ERBB3 mutations achieved PFS at 3 months..

Friday, 5 November 2021 (Version: 20211105AU)

New Enasidenib + Azacitidine in Acute myeloid leukaemia with IDH2 R140, R172: 3

AG221-AML-005. ORR was 50/68 (74%) in the the enasidenib group versus 12/33 (36%) in the azacitidine group. References: 34672961

New Nirogacestat in Adenoid cystic carcinoma with NOTCH1 R2327fs*: 3

Case report. Response of tracheal adenoid cystic carcinoma to the gamma secretase inhibitor with TTP of 6.5 months. References: 10.1200/PO.21.00228

New Nab-sirolimus in Perivascular epithelioid cell tumour with TSC2 Loss-of-function mutations: 3

Phase 2 AMPECT. ORR 89% (8/9) in TSC2 mutant group. ORR 2/16 (13%) in the non-TSC2 mutant group. References: 34637337

New Capivasertib + Paclitaxel in Breast cancer with ESR1+PIK3CA ESR1:protein expression and PIK3CA:oncogenic mutation: R2

Randomized phase 2 study. BEECH. In the PIK3CA+ sub-population, no difference between was found PFS (capivasertib vs placebo: 10.9 v 10.8 months). References:

Changed Olaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations: 1

Comments changed: PBS reimbursed. Requires identification of class 4 or 5 mutation (germline and somatic). SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%). Median PFS was 56.0 months in the olaparib arm versus 13.8 months in the placebo arm.. References changed: 30345884, 34715071.

Friday, 22 October 2021 (Version: 20211022AU)

New Alrizomadlin + Pembrolizumab in Solid tumours with ATM+TP53 ATM:Oncogenic mutations and NOT TP53:Oncogenic mutations: 4

Phase 2 trial (ongoing). NCT03611868. ATM mutant (with wild-type TP53) cohort N=11. ORR 0% and DCR 44%. References: 10.1200/JCO.2021.39.15_suppl.2506

New VX11E in Melanoma with MAP2K2 C125S: 4

Progression biopsy and cell line studies. Mutation conferring on-target acquired resistance to both RAF and MEK inhibition, including C125S, remains sensitive to ERK inhibition. References: 24265153

New Alrizomadlin + Pembrolizumab in Non-small cell lung cancer with STK11 Oncogenic mutations: 4

Phase 2 trial (ongoing). NCT03611868. STK11-mutated lung adenocarcinoma N=5. ORR 0% and DCR 25%. References: 10.1200/JCO.2021.39.15_suppl.2506

New Vemurafenib in Melanoma with MAP2K1 C121S: R2

Progression biopsy study identified MEK C121S as the downstream mechanism for acquired resistance to Vemurafenib. References: 21383288

New Dabrafenib, Trametinib, Dabrafenib + Trametinib in Melanoma with MAP2K2 C125S, V35M, L46F, N126D: R2

Progression biopsy and cell line studies. Acquired C125S (and lesser degree, V35M, L46F, and N126D) confersresistance to both RAF and MEK inhibition. References: 24265153

New Dabrafenib, Trametinib, Dabrafenib + Trametinib in Melanoma with NRAS Q61R, Q61K: R2

Progression biopsy study. Acquired NRAS Q61 mutation confers resistance to both RAF and MEK inhibition. References: 24265153

Removed in Melanoma with BRAF alterations Fusion: Tier 4

Wednesday, 20 October 2021 (Version: 20211020AU)

New LY3009120 in Solid tumours with BRAF A400V, G464V, G466V, G464E, N581S, L597R, K601N, G469A, N581Y, G569R: 4

Class II mutations. A cell line study demonstrating sensitivity to dimer inhibition. References: 26732095

New in Melanoma with BRAF Fusion: 4

References: 31618628

New LY3009120 in Solid tumours with BRAF L485_P490del: 4

Class II mutations. BRAF in-frame deletion in the alpha-C helix favour dimerization and is sensitive to LY3009120 but resistant to Vemurafenib. References: 26732095

New Amivantamab in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 4

CHRYSALIS. NCT02609776. N=16. MET-2 cohort. 4 Confirmed partial responses. References: 10.1016/j.jtho.2021.08.084

New Vemurafenib in Solid tumours with BRAF A400V, G464V, Y519F, E375D, G466V, I326V, G464E, N581S, V226M, L597R, K601N, G469A, G469A, N581Y, G569R: R2

Class II mutations. A cell line study demonstrating lack of sensitivty to vemurafenib. References: 26732095

New LY3009120 in Solid tumours with BRAF L485_P490del: R2

Class II mutations. BRAF in-frame deletion in the alpha-C helix favour dimerization and is sensitive to LY3009120 but resistant to Vemurafenib. References: 26732095

Thursday, 14 October 2021 (Version: 20211014AU)

Changed Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Cisplatin + Paclitaxel, Pembrolizumab + Carboplatin + Paclitaxel in Cervical cancer with CD274 Protein expression: 2

Comments changed: Not TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (13/10/2021). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup.KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS between groups in the PD-L1 CPS < 1 subgroup..

Changed Ipilimumab + Nivolumab in Colorectal cancer with Microsatellite Instability High: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. Phase 2. Checkmate 142. N=45. ORR 69%. DCR 84%. Median PFS and OS not reached after follow up of 24 months. PFS at 24 months: 74%. Responses seen regardless of RAF/RAS mutational status.Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review). References changed: 29355075, 34637336.

Changed Ipilimumab + Nivolumab in Colorectal cancer with Mismatch repair Deficient: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. Phase 2. Checkmate 142. N=45. ORR 69%. DCR 84%. Median PFS and OS not reached after follow up of 24 months. PFS at 24 months: 74%. Responses seen regardless of RAF/RAS mutational status.Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review). References changed: 29355075, 34637336.

Changed Atezolizumab, Atezolizumab + Cobimetinib in Colorectal cancerStable: R2

Biomarker changed: Microsatellite Instability.

Wednesday, 13 October 2021 (Version: 20211013AU)

New Crizotinib, Alectinib in Solid tumours, Histiocytosis, Renal cell carcinoma with ALK Fusion: 4

References: 29079636

Tuesday, 12 October 2021 (Version: 20211012AU)

New Abiraterone Acetate + Leuprorelin, Abiraterone Acetate + Triptorelin, Abiraterone Acetate + Goserelin in Salivary gland cancers with AR Overexpression: 3

Phase 2. NCT02867852. N=24. Median PFS: 3.7 months. Median OS: 22.5 months. ORR 21%. DCR 63%. AR overexpression is defined as combined score expression = 6. References: 34597119

New Ado-Trastuzumab Emtansine in Salivary gland cancers with ERBB2 Amplification: 3

Phase 2 Basket trial. NCT02675829. N=10. ORR 90% (9/10). Median DOR and PFS not reached at follow-up of 12 months. References: 10.1200/JCO.2019.37.15_suppl.6001

New Trastuzumab + Docetaxel in Salivary gland cancers with ERBB2 Amplification, Overexpression: 3

Phase 2. UMIN000009437. N=57. ORR: 70%. CBR: 84%. Median PFS: 8.9 months. Median OS: 39.7 months. References: 30452336

New Crizotinib in Histocytic sarcoma with MET Exon 14 skipping mutation, c.2888-5_2944del: 4

Case report of response Crizotinib in met Exon 14 skipping histocytic sarcoma. References: 25971938

New Durvalumab + Tremelimumab in Colorectal cancer with Tumour Mutational Burden+Microsatellite Tumour Mutational Burden:High and Microsatellite:Stable: 4

Randomized phase 2 study. CCTG CO.26. Durvalumab and tremelimumab combination was associated with an improved OS over best supportive care (6.6 vs 4.1 months). TMB cut off was determined to be 28 mutations per MB (post hoc). POLE status was not determined. References: 32379280

New Durvalumab + Tremelimumab in Colorectal cancer with Tumour Mutational Burden+Mismatch repair Tumour Mutational Burden:High and Mismatch repair:Proficient: 4

Randomized phase 2 study. CCTG CO.26. Durvalumab and tremelimumab combination was associated with an improved OS over best supportive care (6.6 vs 4.1 months). TMB cut off was determined to be 28 mutations per MB (post hoc). POLE status was not determined. References: 32379280

New Enzalutamide in Salivary gland cancers with AR Overexpression: R2

Phase 2. NCT02749903. N=46. ORR 4% (2/46). At 12 months: OS rate 66%, PFS rate 24%. Median PFS was 5.5 months. References: 10.1200/JCO.2019.37.15_suppl.6020

Wednesday, 6 October 2021 (Version: 20211006AU)

New Enasidenib in Myelodysplastic syndrome with IDH2 R140Q, R172K, R172: 3

Phase 1/2. AG221-C-001. ORR 9/17 (53%). Median DOR 9.2 months. Median OS 16.9 months. References: 32145771

New Vorasidenib in Low-grade gliomas, Solid tumours with IDH1 R132H, R132C, R132G, R132L, R132S, R132: 4

Phase 1. NCT02481154. ORR in non-enhancing gliomas was 4/22 (18%). In enhancing gliomas, ORR was 0/30 (0%). In solid tumours, 1/41 responders (2.4%) with median PFS of 1.9 months. References: 34078652

New Vorasidenib in Low-grade gliomas, Solid tumours with IDH2 R140Q, R172K, R172: 4

Phase 1. NCT02481154. ORR in non-enhancing gliomas was 4/22 (18%). In enhancing gliomas, ORR was 0/30 (0%). In solid tumours, 1/41 responders (2.4%) with median PFS of 1.9 months. References: 34078652

New Ivosidenib in Acute myeloid leukaemia with BRAF Oncogenic mutations: R2

RTK pathway mutations are associated with primary resistance to ivosidenib. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with FLT3 Oncogenic mutations: R2

RTK pathway mutations are associated with primary resistance to ivosidenib. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with IDH1 S280F: R2

Sequencing of progression sample revealed S280F at dimer interface resulting in steric hinderence of drug binding in structural modelling, restoring 2HG production. References: 33832922

New Ivosidenib in Acute myeloid leukaemia with IDH1 S280F: R2

References: 32380538

New Ivosidenib in Acute myeloid leukaemia with KIT Oncogenic mutations: R2

RTK pathway mutations are associated with primary resistance to ivosidenib. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with KRAS Oncogenic mutations: R2

RTK pathway mutations are associated with primary resistance to ivosidenib. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with NF1 Oncogenic mutations: R2

RTK pathway mutations are associated with primary resistance to ivosidenib. References: 32380538

New Ivosidenib in Acute myeloid leukaemia with PTPN11 Oncogenic mutations: R2

RTK pathway mutations are associated with primary resistance to ivosidenib. References: 32380538

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification, Overexpression: 2

References changed: 10.1016/j.annonc.2021.08.208710.1016/annonc/annonc741.

Saturday, 2 October 2021 (Version: 20211002AU)

New Gefitinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and C797S, Exon 19 deletion and L718V, E709K and L858R, E709A, S720P, G724S, T725M, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and C797S, L858R and G724S, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Erlotinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and C797S, Exon 19 deletion and L718V, E709K and L858R, E709K and G719S, E709A and G719S, E709A, E709K, G719S, G719A, G719A and L861Q, G719A and R776C, S720P, T725M, I740dupIPVAK, L747S, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, R776H, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Neratinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709K and G719S, E709A and G719S, E709A, E709K, G719S, G719A, G719A and L861Q, G719A and R776C, G719S and T790M, S720P, T725M, I740dupIPVAK, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and V769L, V769L, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L792H, L858R and G724S, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Poziotinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q, L718V, G719S, G719A, G719A and L861Q, G719A and R776C, G719A and T790M, G719S and T790M, S720P, G724S, T725M, I740dupIPVAK, L747P, L747S, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, A767insASV, S768dupSVD, S768dupSVD and V769M, S768I and V769L, S768I and V774M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, V774M, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Afatinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q, L718V, G719S, G719A, G719A and L861Q, G719A and R776C, S720P, G724S, T725M, I740dupIPVAK, L747P, L747S, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and V769L, S768I and V774M, V769L, V774M, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Dacomitinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q, L718V, G719S, G719A, G719A and L861Q, G719A and R776C, S720P, G724S, T725M, I740dupIPVAK, L747P, L747S, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and V769L, S768I and V774M, V769L, V774M, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, E709K and L858R, E709A and G719S, E709A, E709K, G719A and L861Q, G719A and R776C, G719A and T790M, S720P, G724S and T790M, T725M, L747S, L747_K754delInsATSPE, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I, S768I and V774M, S768I and T790M, V774M, R776H, S784F, T790M, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L792H, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and L792H, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L718V, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, G719S, G719A, G719A and R776C, G719A and T790M, G719S and T790M, S720P, T725M, I740dupIPVAK, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and T790M, S784F, T790M, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718V, L858R and T790M and L792H, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Nazartinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and L792H, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L718V, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q and T790M, G719S, G719A, G719A and L861Q, G719A and R776C, G719A and T790M, G719S and T790M, S720P, G724S and T790M, T725M, I740dupIPVAK, L747P, L747S, L747_K754delInsATSPE, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768dupSVD, S768dupSVD and V769M, S768I, S768I and V769L, S768I and V774M, S768I and T790M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, V774M, R776H, R776C, S784F, T790M, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L792H, L861R, L861Q: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Mobocertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, Exon 19 deletion and T790M, E709K and L858R, E709_T710delInsD, G719A and T790M, S720P, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768dupSVD, S768dupSVD and V769M, S768I and V769L, H773insNPH, R776C, S784F, S811F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L861R: 4

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed. References: 34526717

New Osimertinib in Non-small cell lung cancer with EGFR I740_K745dupIPVAIK: 4

Two case reports showing respnses to Osimertinib in metastatic NSCLC harbouring this exon 19 duplication. References: 32216945

New Gefitinib, Erlotinib in Non-small cell lung cancer with EGFR L747_P753delinsS, L747_A750delinsP, Exon 19 indels: 4

Retrospective series. ORR to first generation TKI: L747_P753delinsS (12/24, 50%), L747_A750delinsP (20/23, 87%). References: 33171317

New Telisotuzumab Vedotin in Solid tumours with MET Overexpression: 4

References: 33675179, 10.1200/JCO.2019.37.15_suppl.9023

New Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion and C797S, Exon 19 deletion and T790M and C797S, L718Q, L718Q and T790M, G724S, G724S and T790M, L747P, L747_K754delInsATSPE, A767insASV, S768dupSVD, S768dupSVD and V769M, D770insNPG, H773insNPH, L858R and L718V, L858R and L718Q, L858R and C797S, L858R and T790M and L718Q, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Nazartinib in Non-small cell lung cancer with EGFR Exon 19 deletion and C797S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, L858R and C797S, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion and G724S, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, L718Q, L718Q and T790M, A767insASV, L858R and L718V, L858R and L718Q, L858R and C797S, L858R and T790M and L718Q, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Mobocertinib in Non-small cell lung cancer with EGFR Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and T854I, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, E709K and G719S, E709K, L718Q, L718V, L718Q and T790M, G719S, G724S, G724S and T790M, I740dupIPVAK, L747P, L747S, S768I and T790M, V769L, R776H, L858R and L718V, L858R and L718Q, L858R and C797S, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Gefitinib in Non-small cell lung cancer with EGFR Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and T854I, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, E709_T710delInsD, E709K and G719S, E709A and G719S, L718Q, L718V, L718Q and T790M, G719A, G719A and L861Q, G719A and R776C, G719A and T790M, G719S and T790M, G724S and T790M, I740dupIPVAK, L747P, L747S, L747_K754delInsATSPE, K757R, A767insASV, S768dupSVD, S768dupSVD and V769M, S768I, S768I and V769L, S768I and V774M, S768I and T790M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, V774M, R776C, T790M, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Erlotinib in Non-small cell lung cancer with EGFR Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and T854I, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q, L718V, L718Q and T790M, G719A and T790M, G719S and T790M, G724S, G724S and T790M, L747_K754delInsATSPE, A767insASV, S768dupSVD, S768dupSVD and V769M, S768I and V769L, S768I and T790M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Neratinib in Non-small cell lung cancer with EGFR Exon 19 deletion and L792H, Exon 19 deletion and C797S, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G724S and T790M, L747P, L747S, L747_K754delInsATSPE, A767insASV, S768dupSVD and V769M, S768I, D770insNPG, H773insNPH, V774M, L858R and C797S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Dacomitinib in Non-small cell lung cancer with EGFR Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G719S and T790M, G724S and T790M, L747_K754delInsATSPE, A767insASV, S768dupSVD and V769M, D770insNPG, N771dupN, N771dupN and G724S, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Poziotinib in Non-small cell lung cancer with EGFR Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G724S and T790M, S768I, S768I and T790M, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Afatinib in Non-small cell lung cancer with EGFR Exon 19 deletion and T790M, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G724S and T790M, A767insASV, S768dupSVD and V769M, D770insNPG, H773insNPH, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S: R2

Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed. References: 34526717

New Buparlisib in Solid tumours with PIK3CA Oncogenic mutations; Amplification: R2

Phase 2. NCT01833169. Single-agent Buparlisib has limited clinical activity (ORR 1.4%) in PI3K pathway altered solid tumours. References: 31741715

New Buparlisib in Solid tumours with PIK3R1 Oncogenic mutations: R2

Phase 2. NCT01833169. Single-agent Buparlisib has limited clinical activity (ORR 1.4%) in PI3K pathway altered solid tumours. References: 31741715

New Buparlisib in Solid tumours with PTEN Loss-of-function mutations, loss of protein expression: R2

Phase 2. NCT01833169. Single-agent Buparlisib has limited clinical activity (ORR 1.4%) in PI3K pathway altered solid tumours. References: 31741715

Changed Erlotinib, Gefitinib, Afatinib, Osimertinib in Non-small cell lung cancer with EGFR : 4

Alterations changed: Exon 18 deletion, Exon 18 mutation, E709_T710delinsD, E709K, G719AExon 18 deletion, Exon 18 mutation, E790_T790delinsD, E709K, G917A.

Changed Telisotuzumab Vedotin in Solid tumours with MET Amplification: 4

References changed: 30285518, 34426443, 10.1200/JCO.2019.37.15_suppl.301130285518, 10.1200/JCO.2019.37.15_suppl.3011.

Wednesday, 29 September 2021 (Version: 20210929AU)

New Everolimus in Anaplastic thyroid cancer with TSC2 Loss-of-function mutations, Q1178*: 4

Case report. Exceptional responder to everolimus for 18 months. References: 25295501

New Entrectinib in Solid tumours with KRAS G12C: R2

Cell line study. Bypass mechenism of acquired resistance. References: 31124056

New Everolimus in Anaplastic thyroid cancer with MTOR F2108L: R2

F2108L confers resistance to allosteric mTOR inhibition. References: 25295501

Tuesday, 28 September 2021 (Version: 20210928AU)

New RAF709 + Trametinib in Non-small cell lung cancer with KRAS Q61H: 4

Preclinical study. KRAS Q61H has high affinity to RAS through formation of a cooperative ternary complex with increased MAPK dependency and sensitivity to MEKi and RAFi inhibition. References: 32605999

Monday, 27 September 2021 (Version: 20210927AU)

New Afatinib in Non-small cell lung cancer with EGFR Amplification: 4

Phase 2 EGFR FISH-positive NSCLC. ORR 13%. DCR 51%. References: 25514804

New Afatinib in Non-small cell lung cancer with EGFR Amplification and NOT Oncogenic mutation: 4

Phase 2 EGFR FISH-positive NSCLC. Responders were seen with an ORR 4/43 (9%) in EGFR wild-type amplified patients. PFS 7.9 weeks. References: 25514804

New Gefitinib in Non-small cell lung cancer with EGFR Amplification and NOT Oncogenic mutation: 4

Case report of wild-type amplified EGFR. References: 30622811

New Gefitinib, Erlotinib in Non-small cell lung cancer with EGFR Amplification and NOT Oncogenic mutation: 4

Retrospective study in 502 patients. In 226 patients with EGFR wildtype with amplification (FISH positive) treated with first-generation EGFR TKIs, ORR was 18% (11/62) versus 9% (16/185), and PFS was 4.4 months (FISH-positive) versus 2.0 months (FISH-negative). This is compared to mutation-positive group where ORR was 44% (110/252). References: 23557218

Sunday, 26 September 2021 (Version: 20210926AU)

Changed Pembrolizumab in Urothelial carcinoma with CD274 Protein expression: 1

Comments changed: PBS listed for cisplatin-ineligible urothelial carcinoma with tumours express PD-L1, defined as Combined Positive Score (CPS) >= 10%. TGA approved. In KEYNOTE-052, positive PD-L1 IHC was determined by CPS with 22C3 pharmDx assay. ORR was 24% (38% in CPS >= 10%). Note: pembrolizumab is TGA approved (but not PBS listed) for treatment of advanced urothelial carcinoma after failure of platinum-based chemotherapy. However, this indication is not biomarker-selected. In KEYNOTE-045, pembrolizumab as second-line monotherapy yielded significantly longer OS than chemotherapy (where higher OS benefit vs chemotherapy was seen in subgroups with both CPS >=1% and >= 10%).PBS reimbursed. TGA approved for cisplatin-ineligible patients with tumours express PD-L1. In KEYNOTE-052, positive PD-L1 IHC was determined by with Combined Positive Score (22C3 pharmDx assay). Overall ORR was 24% (38% in CPS >= 10%)..

Changed Pembrolizumab in Colorectal cancer with Mismatch repair Deficient

Tier changed: 1B. Comments changed: PBS listed. TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, the PFS was not significantly different. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC..

Changed Pembrolizumab in Colorectal cancer with Mismatch repair Deficient

Tier changed: 1B. Comments changed: PBS listed. TGA approved. KEYNOTE-164: KEYNOTE-164: In previously treated metastatic colorectal cancer, ORR was 33% and median OS was 31.4mo. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.TGA approved. KEYNOTE-164: Previously treated. ORR 33%. Median OS 31.4mo. MSI-H defined as PCR-based analysis of microsatellite loci by local testing..

Changed Pembrolizumab in Colorectal cancer with Microsatellite Instability High: 1B

Comments changed: TGA approved. KEYNOTE-177: First-line treatment for metastatic CRC. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. MSI-H is defined as PCR-based analysis of 3-5 tumor microsatellite loci by local testing.TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, the PFS was not significantly different. MSI-H defined as PCR-based analysis of 3-5 tumor microsatellite loci by local testing..

Changed Pembrolizumab in Colorectal cancer with Microsatellite Instability High: 1B

Comments changed: TGA approved. KEYNOTE-164: In previously treated metastatic colorectal cancer, ORR was 33% and median OS was 31.4mo. MSI-H is defined as PCR-based analysis of microsatellite loci by local testing.TGA approved. KEYNOTE-164: Previously treated. ORR 33%. Median OS 31.4mo. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC..

Changed Pembrolizumab in Colorectal cancer with KRAS+Microsatellite Instability KRAS:Oncogenic mutations AND Microsatellite Instability:High: R2

Comments changed: KRAS subgroup showed no PFS benefit over chemotherapy in KEYNOTE-177KRAS subgroup showed no PFS benefit in KEYNOTE-177.

Changed Pembrolizumab in Colorectal cancer with KRAS+Mismatch repair KRAS:Oncogenic mutations AND Mismatch repair:deficient: R2

Comments changed: KRAS subgroup showed no PFS benefit over chemotherapy in KEYNOTE-177KRAS subgroup showed no PFS benefit in KEYNOTE-177.

Thursday, 23 September 2021 (Version: 20210923AU)

New Poziotinib in Non-small cell lung cancer with ERBB2 A775_G776insYVMA, G778_P780dup, G776delinsVC, Exon 20 insertion, Exon 20 mutation: 3

N=30. NSCLC subsequent to platinum-based chemotherapy. ORR 27%. Median DOR 5.0 months. Median PFS 5.5 months. Median OS 15 months. References: 34550757

New GSK343 in Multiple myeloma with KDM6A Loss-of-function mutations: 4

Loss of UTX enhances sensitizes multiple myeloma cells to EZH2 inhibition. References: 29045832

New Pembrolizumab, Nivolumab + Ipilimumab in Pancreatic adenocarcinoma with Mismatch repair Deficient: 4

Retrospective series. N=6 (evaluable). Median PFS 8.2 months. References: 10.1200/JCO.2021.39.3_suppl.415

Changed Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Cisplatin + Paclitaxel, Pembrolizumab + Carboplatin + Paclitaxel in Cervical cancer with CD274 Protein expression: 2

References changed: 3453442910.1056/NEJMoa2112435.

Changed Fam-trastuzumab deruxtecan-nxki in Non-small cell lung cancer with ERBB2 S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, G778_P780dup, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation: 2

References changed: 34534430, 10.1016/annonc/annonc74110.1056/NEJMoa2112431, 10.1016/annonc/annonc741.

Monday, 20 September 2021 (Version: 20210920AU)

New Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification, Overexpression: 2

Phase 3 DESTINY-Breast03: PFS was significantly longer in patients treated with trastuzumab deruxtecan (T-DXD, 25.1 months) vs trastuzumab emtansine (T-DM1, 7.2 months). Confirmed ORR: 79% (T-DXD) vs 34% (T-DM1). References: 10.1016/annonc/annonc741

New Fam-trastuzumab deruxtecan-nxki in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression, Protein expression AND Amplification: 2

Phase 2. DESTINY-Gastric02: N=79. Single-arm trial of trastuzumab deruxtecan in patients previously treated with trastuzumab. ORR 38% (30/79). Median PFS 5.5 months. Median DOR 8.1 months. References: 10.1016/annonc/annonc741

New Adagrasib in Colorectal cancer with KRAS G12C: 3

KRYSTAL-1: Multicohort phase 1/2. Adagrasib monotherapy: ORR 22% (10/45). DCR 87% (39/45). Median DOR: 4.2 months and median PFS 5.6 months. References: 10.1016/annonc/annonc741

New Adagrasib + Cetuximab in Colorectal cancer with KRAS G12C: 3

KRYSTAL-1: Multicohort phase 1/2. Adagrasib and cetuximab combination: ORR 43% (12/28). DCR 100%. References: 10.1016/annonc/annonc741

New Adavosertib in Colorectal cancer with TP53+KRAS TP53:Oncogenic mutations AND KRAS:G12, TP53:Oncogenic mutations AND KRAS:G13: 3

FOCUS4-C: Phase 2 KRAS and TP53 mutant treatment-refractory CRC. N=69. Adavosertib was associated with PFS improvement (primary endpoint) over active monitoring (3.6 v 1.9 months). OS not significantly improved. PFS Benefits were seen in the subgroups of left-sided primary tumour location and KRAS codon 12/13. References: 10.1200/JCO.21.01435

Changed Nivolumab + FOLFOX, Nivolumab + CAPOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CD274 Protein expression: 2

Comments changed: Not TGA approved. CheckMate 649: Phase III, First-line, HER2-negative gastric/GOJ carcinoma. Nivolumab plus chemotherapy improved PFS (7.7 vs 6.0 months) over chemotherapy alone in PD-L1 positive population. PD-L1 positivity was defined as CPS ≥ 5%.Not TGA approved. CheckMate 649: Phase III, First-line, HER2-negative gastric/GOJ carcinoma. PD-L1 positivity defined as CPS ≥ 5%. References changed: 34102137, 10.1016/j.annonc.2020.08.2296, 10.1016/annonc/annonc741.

Changed Fam-trastuzumab deruxtecan-nxki in Non-small cell lung cancer with ERBB2 S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, G778_P780dup, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation: 2

References changed: 10.1056/NEJMoa2112431, 10.1016/annonc/annonc741.

Sunday, 19 September 2021 (Version: 20210919AU)

New Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Cisplatin + Paclitaxel, Pembrolizumab + Carboplatin + Paclitaxel in Cervical cancer with CD274 Protein expression: 2

KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS between groups in the PD-L1 CPS < 1 subgroup. References: 10.1056/NEJMoa2112435

New Fam-trastuzumab deruxtecan-nxki in Non-small cell lung cancer with ERBB2 S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, G778_P780dup, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation: 2

DESTINY-Lung01. Phase 1/2. N=91. ORR 50/91 (55%). Median DOR 9.3 months. Median PFS 8.2 months. Median OS 17.8 months. DCR 84/91 (92%). References: 10.1056/NEJMoa2112431

New Erlotinib in Non-small cell lung cancer with EGFR EGFR-RAD51 fusion: 4

References: 27102076

New Afatinib + Bevacizumab in Non-small cell lung cancer with EGFR KIF5B-EGFR fusion: 4

References: 32903808

Friday, 17 September 2021 (Version: 20210917AU)

Changed Mobocertinib in Non-small cell lung cancer with EGFR Exon 20 insertion

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 15/09/2021. NCT02716116: Phase 1/2 trial. ORR to TAK-788 was 43% in 28 patients who had exon 20 insertion. Median DOR was 14 months. Median PFS was 7.3 months.NCT02716116: Phase 1/2 trial. 28 / 136 patient had exon 20 insertion. ORR to TAK-788 was 43%..

Thursday, 16 September 2021 (Version: 20210916AU)

New Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline): 2

Not TGA approved. FDA approved 13/08/2021. Study 004. N=61. ORR 36% (22/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%. ORR 80% (16/20) for PNET and 32% (16/50) CNS hemangioblastomas. References: 10.1200/JCO.2021.39.15_suppl.4555

Wednesday, 15 September 2021 (Version: 20210915AU)

New Mirdametinib in Solid tumours with KRAS G60_A66dup, E62_A66dup, Switch 2 duplication, Exon 3 insertion: 4

Preclinical study showing KRAS Switch II duplication is oncogenic and sensitive to MEK inhibition. References: 26854029

Friday, 10 September 2021 (Version: 20210910AU)

New Talazoparib in Prostate cancer with BRCA2 Oncogenic mutations: 3

TALAPRO-1. Phase 2. ORR 46% (26/57). References: 34388386

New Talazoparib in Prostate cancer with ATM Oncogenic mutations: 4

TALAPRO-1. Phase 2. N=17. 2 responders. 3/6 patients had circulating tumour cell conversion (from >=5 to <5 cells per 5-7 mL of blood). References: 34388386

New Talazoparib in Prostate cancer with BRCA1 Oncogenic mutations: 4

TALAPRO-1. Phase 2. N=4. PR 2/4. References: 34388386

New Talazoparib in Prostate cancer with PALB2 Oncogenic mutations: 4

TALAPRO-1. Phase 2. N=4. 1 PR. References: 34388386

New Talazoparib in Prostate cancer with CHEK2 Oncogenic mutations: R2

TALAPRO-1. Phase 2. N=9. ORR 0%. References: 34388386

Tuesday, 7 September 2021 (Version: 20210907AU)

New Ensartinib in Non-small cell lung cancer with ALK Fusion: 2

Phase 3. eXalt3. Median PFS of Ensartinib was 25.8 months versus 12.7 months (Crizotinib) in the first-line metastatic setting. References: 10.1001/jamaoncol.2021.3523

New Sacituzumab Govitecan in Triple-negative breast cancer with TACSTD2 Protein expression, Overexpression: 3

Pre-specified biomarker analysis from the phase 3 ASCENT trial. High and medium Trop2 expression were associated with higher magnitude of PFS and OS benefit versus standard-of-care chemotherapy. References: 34116144

New Lorlatinib in High-Grade Gliomas with ALK SPECC1L-ALK fusion: 4

Case of a paediatric high-grade glioma harbouring SPECC1L-ALK fusion demonstrating deep and durable response to lorlatinib. References: 34407349

New Alectinib in Breast Cancer with ALK STRN-ALK fusion: 4

Case report. References: 10.1200/PO.21.00142

New Ruxolitinib in Acute lymphoblastic leukaemia with JAK2 PCM1-JAK2 fusion: 4

Case report. References: 33502001

New Ruxolitinib in Chronic eosinophilic leukaemia with JAK2 PCM1-JAK2 fusion: 4

Case report. Complete cytogenetic response. References: 22899477

New Larotrectinib in Ependymoma with NTRK2 KANK1-NTRK2 fusion: 4

Case report. References: 10.1200/PO.20.00375

Removed Palbociclib + Avelumab in Solid tumours with CCND1 alterations Amplification: Tier 4

Removed Palbociclib + Avelumab in Solid tumours with CCND2 alterations Amplification: Tier 4

Removed Palbociclib + Avelumab in Solid tumours with CCND3 alterations Amplification: Tier 4

Removed Palbociclib + Avelumab in Solid tumours with CDK4 alterations Amplification: Tier 4

Removed Palbociclib + Avelumab in Solid tumours with CDKN2A alterations Oncogenic mutations, deletions, Truncating mutations, Loss-of-function mutations: Tier 4

Changed Ivosidenib in Cholangiocarcinoma with IDH1 R132: 2

Comments changed: Not TGA approved. FDA approved (25/08/2021). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months).Not TGA approved. ClarIDHy trial.

Changed ETC-159 in Pancreatic adenocarcinoma with RNF43 : 4

Alterations changed: Truncating mutations, Frameshift mutations, C-terminal truncating mutations, Loss-of-function mutations, Oncogenic mutations, Deletion, R371fs, G659fs, P660fsTruncating mutations, Frameshift mutations, C-terminal truncating mutations, Loss-of-function mutations, Oncogenic mutations, R371fs, G659fs, P660fs.

Wednesday, 18 August 2021 (Version: 20210818AU)

New Avapritinib in Gastrointestinal stromal tumour with KIT Oncogenic mutations, V654A, T670I, Exon 17 mutation: 3

Phase 3. VOYAGER. Avaprintinib vs Regorafenib in biomarker unselected third/fourth-line setting. In non-PDGFRA D842V-mutants, ORR was 16% (38/233). Note Avaprintinib showed no PFS benefit over regorafenib. References: 34343033

New Atezolizumab in Colorectal cancer with Microsatellite Instability High: 4

Phase 3 IMBlaze 370. MSI-H subgroup. 3/6 response (50%) in MSI high group. References: 31003911

New Atezolizumab, Atezolizumab + Cobimetinib in Colorectal cancer with Microsatellite Stable: R2

Phase 3. IMBlaze370. ORR 4/273 (1%) in the Atezolizumab groups. References: 31003911

Changed Avapritinib in Gastrointestinal stromal tumour with PDGFRA Exon 18 mutation, D842V, D842_H845del: 2

Comments changed: Not TGA approved; FDA approved. NAVIGATOR trial; First-line. At 300 mg (RP2D). ORR was 93% (26/28) and CBR was 100%..

Changed Avapritinib in Gastrointestinal stromal tumour with KIT Oncogenic mutations, Exon 11 mutation, Exon 9 mutation, D816E, D816F, D816I, D816V, D816Y, V560G, V559D, D820E, Y823D, D820Y, D557

Tier changed: 32.

Friday, 13 August 2021 (Version: 20210813AU)

New Cabozantinib in Gastrointestinal stromal tumour with KIT Protein expression, Oncogenic mutation, Exon 9 mutation, Exon 11 mutation: 3

Phase 2. CaboGIST. NCT02216578. N=50. Cabozantinib following failure of imatinib, sunitinib, and regorafenib. At 12 weeks, ORR 14%. DCR 82%. Median PFS 5.5 months. References: 32470848

New Cabozantinib in Mastocytosis with KIT D816V: 4

Single case report of telangectasia macularis eruptiva perstans that harbours KIT D816V with clinical response. References: 10.1016/j.jaad.2014.01.550

New Cabozantinib in Gastrointestinal stromal tumour with KIT Exon 9 mutations, A502_Y503dup, Exon 11 mutations, K558_G565delinsR, Exon 17 mutations, D820G: 4

Drug sensitivity screening in GIST xenografts with different KIT mutations. References: 27777285

New Cabozantinib in Gastrointestinal stromal tumour with KIT V559G, T670I, V654A, D816E, D820E, D820G, D820Y, N822K, A829P, V560_Y578del, K624E: 4

Drug sensitivity screen. References: 21926191

New Cabozantinib in Gastrointestinal stromal tumour with MET Y1248H, D1246N, K1262R: 4

References: 21926191

New Cabozantinib in Gastrointestinal stromal tumour with KIT V559A, V559D, D816H, D816V: R2

Drug sensitivity screen. References: 21926191

Thursday, 12 August 2021 (Version: 20210812AU)

New Encorafenib + Binimetinib in Colorectal cancer with BRAF V600E, V600K: 3

Phase 2. NCT01543698. N=11. ORR: 2/11 (18%). DCR at 6 months: 7/11 (64%). References: 32669376

Tuesday, 10 August 2021 (Version: 20210810AU)

Changed Selpercatinib in Medullary thyroid cancer with RET : 2

Alterations changed: Oncogenic mutations and NOT Amplification, M918T, V804M, V804L, C609, C611, C618, C620, C630, C634, D631_L633delinsE, E632_L633del, A883F, D631_L633delinsV, L790F, D898_E901del, D903_S904delinsEP, K666N, T636_V637insCRT, D378_G385delinsEOncogenic mutations and NOT Amplification, M918T, V804M, V804L, C609, C611, C618, C620, C630, C634, D631_L633delinsE, E632_L633del, A883F, D631_L633delinsV, L790F, D898_E901del, D903_S904delinsEP, K666N T636_V637insCRT, D378_G385delinsE.

Changed Dacomitinib in Glioblastoma with EGFR : 4

Alterations changed: Amplification AND G598VAmplification + G598V.

Changed Afatinib + Temozolomide in Glioblastoma with EGFR : 4

Alterations changed: vIII AND D247YvIII + D247Y.

Changed Cabozantinib in Non-small cell lung cancer with MET : 4

Alterations changed: Exon 14 deletion, Exon 14 splicing mutation, Exon 14 skipping mutation, Y1003, D1010, Amplification, D1228, G1163Exon 14 deletion, Exon 14 splicing mutation, Exon 14 skipping mutation, Y1003, D1010, amplifications, D1228, G1163.

Changed Seribantumab in Solid tumours with NRG1 : 4

Alterations changed: Fusion; CD74-NRG1 fusion; VAMP2-NRG1 fusion; SLC3A2-NRG1 fusionFusion; CD74-NRG1fusion; VAMP2-NRG1 fusion; SLC3A2-NRG1 fusion.

Changed Adagrasib in Solid tumours with RET : R2

Alterations changed: CCDC6-RET fusionCCD6-RET fusion.

Friday, 6 August 2021 (Version: 20210806AU)

New Ipatasertib + FOLFOX in Gastroesophageal junction adenocarcinoma, Gastric Cancer with PIK3CA Oncogenic mutations, E542K, E545K, E545, H1074R, Q546X: R2

Randomised phase 2 trial. JAGUAR. No significant PFS benefit was observed in the addition of ipatasertib to FOLFOX or in subgroups with PI3KCA/AKT-alteration. References: 30592991

New Ipatasertib + FOLFOX in Gastroesophageal junction adenocarcinoma, Gastric Cancer with PTEN Oncogenic mutations, Loss-of-function mutations, Loss of protein expression: R2

Randomised phase 2 trial. JAGUAR. No significant PFS benefit was observed in the addition of ipatasertib to FOLFOX or in subgroups with PI3KCA/AKT-alteration. References: 30592991

Wednesday, 4 August 2021 (Version: 20210804AU)

New Trastuzumab + Pertuzumab in Biliary tract cancers, Cholangiocaricnoma, Gallbladder cancer, Ampullary carcinoma with ERBB2 Amplification; Overexpression: 3

Phase 2. MyPathway basket trial. Trastuzumab and Pertuzumab in biliary tract cancers: ORR 9/39 (23%). DCR: 20/39 (51%). PFS 4.0 months. DOR: 10.8 months. Responders were seen in extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinomas. References: 34339623

New Nivolumab in Glioblastoma with MSH2 R359S (germline): 4

Case report of prolonged response to Nivolumab. References: 33140187

New Nivolumab in Glioblastoma with PMS2 K706Sfs: 4

Case series. Germline PMS2 homozygous mutant. All tumours are hypermutants with ultrahigh TMB. Two cases (paediatric) had significant clinical and radiological responses to single agent Nivolumab. References: 27001570

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in High-grade gliomas, Anaplastic astrocytoma, Glioblastoma with Mismatch repair Deficient: R2

A case-control series showed no response to PD-L1 blockade in 11 HGG patients with hypermutant and mismatch repair-deficient HGG. High TMB is associated with few clonal neoantigens and no immunogenic responses in glioma populations. References: 32322066

New Imatinib in Sarcoma, Intimal sarcoma with PDGFRA Amplification: R2

Single-centre experience of case series in intial sarcomas. No objective response to imatinib in 4 patients treated with PDGFR amplification. References: 28501860

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in High-grade gliomas, Anaplastic astrocytoma, Glioblastoma with Tumour Mutational Burden High: R2

A case-control series showed no response to PD-L1 blockade in 11 HGG patients with hypermutant and mismatch repair-deficient HGG. High TMB is associated with few clonal neoantigens and no immunogenic responses in glioma populations. References: 32322066

Changed Therapy in Uterine serous carcinoma, Endometrial cancer with ERBB2 Amplification, Overexpression, Oncogenic mutations, V842I: 3

Therapy changed: Trastuzumab + PertuzumabPertuzumab + Trastuzumab.

Tuesday, 3 August 2021 (Version: 20210803AU)

New Olaparib in Uterine serous carcinoma with BRIP1 Loss-of-function mutations: 4

Case report. BRIP Q554Hfs*35. Complete response after treatment with olaparib for at least 9 months. References: 32923896

New H3Mab-17 in Colorectal cancer with ERBB3 Overexpression: 4

References: 34184091

Changed Amivantamab in Non-small cell lung cancer with EGFR Exon 20 insertion: 2

Comments changed: Not TGA approved. FDA accelerated approval 21/05/2021. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months.Not TGA approved. FDA accelerated approval 21/05/2021. CHRYSALIS. ORR 36%. References changed: 34339292, 32414908, 10.1200/JCO.2020.38.15_suppl.9512.

Monday, 26 July 2021 (Version: 20210726AU)

Changed Binimetinib + Encorafenib in Melanoma with BRAF V600E, V600K: 1

Comments changed: TGA approved. PBS reimbursed. COLUMBUS trial.TGA approaved. PBS reimbursed. COLUMBUS trial..

Friday, 23 July 2021 (Version: 20210723AU)

Thursday, 22 July 2021 (Version: 20210722AU)

Changed Lenvatinib + Pembrolizumab in Endometrial cancer with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: 1B

Comments changed: TGA provisional approval. FDA Approved. In KEYNOTE-146: ORR was 38% (out of 94 patients) including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS). In the confirmatory trial (KEYNOTE-775), primary point was met in non-MSI-H/dMMR patients who have progressed through one previous line of platinum-based chemotherapy: median PFS was 6.6 (pembrolizumab + lenvatinib) vs 3.8 months (investigator choice of chemotherapy) and median OS: 17.4 vs 12 months (chemotherapy). ORR: 30% vs 15%.TGA/FDA provisional approval. KEYNOTE-146. ORR 38% of 94 patients, including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS)..

Changed Ipatasertib + Abiraterone in Prostate cancer with PTEN Loss of protein expression; Loss-of-function mutations: 2

Comments changed: Not TGA approved. IPATential150. Radiological PFS of predefined subgroup by PTEN loss by IHC (co-primary endpoint) was significantly higher (18.5 months) in the ipatasertib group (vs 16.5 months in the abiraterone only group). Radiological PFS also corresponds to percentage of PTEN loss in tumour cells and PTEN loss by NGS.Not TGA approved. IPATential150. Predefined NGS concordant with IHC.. References changed: 34246347, 10.1016/j.annonc.2020.08.2250NCT03072238, 10.1016/j.annonc.2020.08.2250.

Changed ETC-159 in Pancreatic adenocarcinoma with RNF43 Truncating mutations, Frameshift mutations, C-terminal truncating mutations, Loss-of-function mutations, Oncogenic mutations, R371fs, G659fs, P660fs: 4

Comments changed: RNF43 truncating and frameshift mutations, and are sensitive to PORCN inhibitors in cell line assay.RNF43 truncating and frameshift mutations are sensitive to PORCN inhibitors.

Wednesday, 21 July 2021 (Version: 20210721AU)

New ETC-159 in Pancreatic adenocarcinoma with RNF43 Truncating mutations, Frameshift mutations, C-terminal truncating mutations, Loss-of-function mutations, Oncogenic mutations, R371fs, G659fs, P660fs: 4

RNF43 truncating and frameshift mutations are sensitive to PORCN inhibitors. References: 33067269

Changed Therapy in Solid tumours with RNF43 Oncogenic mutations: 4

Therapy changed: Wnt-C59PORCN inhibitor.

Tuesday, 20 July 2021 (Version: 20210720AU)

New Cabozantinib in Non-small cell lung cancer with RET Fusions, KIF5B-RET fusion: 4

Case report. Best response is SD for 9 months. References: 30653139

Changed Cabozantinib in Non-small cell lung cancer with RET : 4

Alterations changed: Fusions, TRIM33-RET fusion, KIF5B-RET fusion. Comments changed: Case series from a Phase 2 study of XL-184 in RET-positive NSCLC. Two responders. DOR not reported.Not TGA approved. Case reports only. References changed: 23533264, 30653139.

Tuesday, 13 July 2021 (Version: 20210713AU)

New ABN401 in Solid tumours with MET Amplification, Overexpression, Exon 14 skipping mutation: 4

References: 32549194

Monday, 12 July 2021 (Version: 20210712AU)

New Afatinib in Non-small cell lung cancer with EGFR E709_T710delinsD: 4

Case report. Partial response to afatinib with clinical benefit of 23 months. References: 34178699

New Afatinib in Non-small cell lung cancer with EGFR E709_T710delinsD: 4

Case report. Both CT and metabolic response to afatinib. References: 28625646

New Gefitinib in Non-small cell lung cancer with EGFR E709_T710delinsD: 4

Case report. References: 22982663

New Gefitinib, Erlotinib in Non-small cell lung cancer with EGFR E709_T710delinsD, L747P, V774M, F784F, K806E, N826Y, N842S, T847I, V851I: R2

No responders in patients harbouring certain uncommon mutations in retrospective series. References: 21531810

Changed Therapy in Non-small cell lung cancer with EGFR : 4

Therapy changed: Erlotinib, Gefitinib, Afatinib, OsimertinibErlotinib, Gefitinib, Osimertinib. Alterations changed: Exon 18 deletion, Exon 18 mutation, E790_T790delinsD, E709K, G917A. Comments changed: OncoKB LOE 3. Cell line study. In Ba/F3 cells transfected with exon 18 deletion or mutations, Afatinb demonstrated higher relative sensitivity (IC90) than Gefitinib, Erlotinib, as well as third-generation TKIs Osimertinib and CO1686..

Sunday, 11 July 2021 (Version: 20210711AU)

New Mirvetuximab soravtansine in Ovarian cancer with FOLR Overexpression: 3

Phase 3. FORWARD I. In patient with platinum-resistant ovarian cancer, mirvetuximab soravtansine did improvement in PFS compared with chemotherapy versus chemotherapy in patients. In exploratory analysis, however, ORR (24% vs 10%), CA-125 response, as well as PFS and OS improvement over chemotherapy were seen in FR alpha-high subgroup (N=147). References: 33667670

Saturday, 10 July 2021 (Version: 20210710AU)

New GSK2636771 in Gastric cancer with PTEN Loss-of-function mutations, loss of protein expression: 3

References: 10.1016/j.annonc.2021.05.034

New Crizotinib in Non-small cell lung cancer with ROS1 SLC12A2-ROS1 fusion: 4

Case report. References: 33682977

Changed Enfortumab Vedotin in Urothelial carcinoma with NECTIN4 Protein expression: 2

Comments changed: Not TGA approved. FDA approved. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells.Not TGA approved. FDA accelerated approval. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells..

Thursday, 8 July 2021 (Version: 20210708AU)

New Encorafenib + capmatinib in Colorectal cancer with BRAF+MET Amplification: 4

Case report: MET amplification was identified as the off-target resistance mechanism to Encorafenib + cetuximab and was sensitive to incorporation of type I c-met inhibitor. References: 10.1200/PO.21.00107

New Imatinib + Hydroxyurea in Glioblastoma with KIT Amplification: 4

Negative phase 2 study in GBM patients with ORR of 3.5% and CBR of 23% in unselected population. Note: exploratory biomarker analysis identified a single case -KIT amplification was identified by FISH had SD for 9.7 months (overall cohort PFS 5.6 months). KIT copy number not quantified. References: 19904263

New Encorafenib + binimetinib + cetuximab, Encorafenib + cetuximab in Colorectal cancer with BRAF+MET Amplification: R2

Case report: MET amplification was identified as the off-target resistance mechanism to Encorafenib + cetuximab and was sensitive to incorporation of type I c-met inhibitor. References: 10.1200/PO.21.00107

New Gefitinib in Non-small cell lung cancer with EGFR L747_A750delinsP: R2

Case report of primary Gefitinib resistance. TP53 co-mutation was present. References: 32883519

New Gefitinib, Erlotinib in Non-small cell lung cancer with EGFR T751_I759delinsS, S752_I759del: R2

Retrospective study. EGFR exon 19 deletion with starting codon of T751or S752 have a comparatively shorter median PFS. References: 32418166

Wednesday, 7 July 2021 (Version: 20210707AU)

Removed Ibrutinib in Waldenstroms macroglobulinaemia with CXCR4 alterations Oncogenic mutations: Tier 2

Removed Palbociclib + Avelumab in Solid tumours with CDK6 alterations Amplification: Tier 4

Changed Ado-Trastuzumab Emtansine in Breast cancer with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Changed Lapatinib + Capecitabine in Breast cancer with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Changed Trastuzumab in Breast cancer with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Changed Trastuzumab + Capecitabine in Breast cancer with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Changed Trastuzumab + Paclitaxel in Breast cancer with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Changed Trastuzumab + Pertuzumab + Docetaxel in Breast cancer with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Changed Trastuzumab + Capecitabine + Oxaliplatin in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Changed Trastuzumab + Cisplatin + Fluorouracil, Trastuzumab + Cisplatin + Capecitabine in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 : 1

Alterations changed: Amplification, Overexpression.

Tuesday, 6 July 2021 (Version: 20210706AU)

New Pyrotinib + Capecitabine in Breast cancer with ERBB2 Amplification, Overexpression: 2

Phase 3. PHOEBE. Patients treated with pyrotinib with capecitabine had longer PFS (12.5 mo) vs Lapatinib and capacitabine (6.8 months) in HER2-positive breast cancers. HER2-positivity defined as IHC 3+ or amplification identified on FISH. References: 33581774

New Pyrotinib in Breast cancer with ERBB2 S310F, S310Y, L403V, L755S, D769Y, A775_Y776insYVMA, V777L, T862A: 4

References: 33145402

New Pemigatinib in Cholangiocarcinoma with FGFR2 FGFR2-NRBF2 fusion, FGFR2-KIAA1217 fusion, FGFR2-CCDC170 fusion, FGFR2-AHCYL1 fusion, FGFR1-WDHD1 fusion, FGFR2-PAWR fusion, FGFR2-ATAD2 fusion, FTFR2-TRIM8 fusion: 4

Exploratory analysis in patients with clinical benefits in the FIGHT-202 trial. References: 33218975

New GSK343, EPZ6438 in High-grade gliomas, Diffuse intrinsic pontine glioma, H3K27M-mutant glioma with H3F3A K27M, K28M: 4

EZH2 activities is required for growth of DIPG cells in cell line models of pediatric gliomas. All H3K27M cell lines were sensitive to EZH2 inhibition. The inhibition of EZH2 is dependent on function of p16INK4A. References: 28263309

New Pemigatinib in Cholangiocarcinoma with FGFR2 N549K, N549H, E565A, L617V, K641R, K659M: R2

Exploratory analysis of on-target secondary mutations from FIGHT-202 trial. No gatekeepter V564 mutations were identified. References: 33218975

Changed Atezolizumab + nab-Paclitaxel in Triple-negative breast cancer with CD274 Protein expression: 1B

Comments changed: TGA provisional approval based on PFS data. Not PBS reimbursed. IMpassion130. PD-L1 positive is defined as >= 1% immune cells as percentage of tumour area. (IC1/2/3). Note: In the ITT population, the OS was 21.0 months in the Atezolizumab group vs 18.7 months in the placebo group (not statistically significant), with an exploratory signal of OS improvement seen in the subgroup analysis in the PD-L1 IC-positive population (25.4 vs 17.9 months).. References changed: 30345906, 34219000.

Changed Pyrotinib in Non-small cell lung cancer with ERBB2 A775_G776insYVMA, G776ins, G776R, G776C, P780_Y781insGSP, V777L: 3

Comments changed: Phase 2. N=60. Previously treated NSCLC. ORR: 30%. DOR: 6.9mo. Median PFS: 6.9mo. NCT02834936.

Changed Pyrotinib + Capecitabine in Breast cancer with ERBB2 Amplification: 3

Comments changed: Randomized phase 2. ORR Pyrotinib + capecitabine was 79%. Median PFS 18.1 months..

Saturday, 3 July 2021 (Version: 20210703AU)

New Mogamulizumab in Cutaneous T-cell lymphoma, Sézary syndrome, Mycosis fungoides with CCR4 Protein expression: 1B

FDA approved. Phase 3 MAVORIC trial. Comparing with vorinostat, mogalizumab extended the PFS to 7.7 vs 3.1 months (vorinostat) in previously treated cutaneous T-cell lymhpomas. Exploratory analysis showed that CCR4 expression was ubiquitously expressed (97% had at least 10% infiltrating lymphoid cells), but CCR4 was not a requirement for participation. References: 30100375

Friday, 2 July 2021 (Version: 20210702AU)

New Pimitespib in Gastrointestinal stromal tumour with KIT Protein expression, Oncogenic mutations: 2

Phase 3. CHAPTER-GIST-301. Single-agent Pimitespib in treat-refractory GIST patients after imatinib, sunitinib, and regorafenib failure. Median PFS was 2.8 vs. 1.4 mo (placebo). Median OS: 13.8 vs 9.6 mo (placebo). Pimitespib was also effective in patients who had secondary KIT resistance. References: 10.1200/JCO.2021.39.15_suppl.11524

New Pimitespib in Gastrointestinal stromal tumour with PDGFRA Oncogenic mutations: 2

Phase 3. CHAPTER-GIST-301. Single-agent Pimitespib in treat-refractory GIST patients after imatinib, sunitinib, and regorafenib failure. Median PFS was 2.8 vs. 1.4 mo (placebo). Median OS: 13.8 vs 9.6 mo (placebo). Pimitespib was also effective in patients who had secondary KIT resistance. References: 10.1200/JCO.2021.39.15_suppl.11524

New Olutasidenib in Acute myeloid leukaemia with IDH1 R132: 3

Phase 2. NCT02719574. Interim anaylsis. ORR 57% (46/123). CR 30% (37/123). Median OS 10.5 months with duration of treatment 5.5 months. References: 10.1200/JCO.2021.39.15_suppl.7006

New Nivolumab in Solid tumours with POLE P286R, V411L: 3

Phase 2. AcSé. NCT03012581. N=15 (10 evaluable). Mismatch proficient tumours with POLE exonuclease domain mutations. Responders were seen in three patients with P286R and V411L mutations and in colorectal and cervical cancers. No response in non-pathogenic mutations. References: 10.1016/j.annonc.2020.08.640

Changed Binimetinib + Encorafenib in Melanoma with BRAF V600E, V600K: 1

Comments changed: TGA approaved. PBS reimbursed. COLUMBUS trial.TGA approaved. PBS reimbursed. COLOMBUS trial.. References changed: 30219628, 10.1200/JCO.2021.39.15_suppl.9507.

Changed Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2+KRAS ERBB2:Amplification and ERBB2:Protein expression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E, ERBB2:Overexpression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E: 3

References changed: 33961795, 10.1200/JCO.2020.38.15_suppl.4000, 10.1200/JCO.2021.39.15_suppl.3505.

Thursday, 1 July 2021 (Version: 20210701AU)

New Pertuzumab + Trastuzumab in Uterine serous carcinoma, Endometrial cancer with ERBB2 Amplification, Overexpression, Oncogenic mutations, V842I: 3

Phase 2. TAPUR. DCR at 16 weeks: 37%, which met the primary endpoint. Note 1 patient had ERBB3 amplification. ORR 7.1%. References: 10.1200/JCO.2021.39.15_suppl.5508

New Vistusertib + Anastrozole in Endometrial cancer with ESR1 Protein expression: 3

Randomized phase 2: VICTORIA. N=73. In ER/PR-positive endometrial carcinoma, progression-free rate at 8 weeks was 67% vs 39%. ORR: 25% (combination) vs 17.4% (anastrozole alone). References: 10.1200/JCO.2021.39.15_suppl.5507

New Mirvetuximab soravtansine + Bevacizumab in Ovarian cancer with FOLR Protein expression: 3

Phase 1b FORWARD II trial. N=60. ORR 47%. In patients with high FR expression, confirmed ORR was 64%. In platinum-resistance disease with high FR expression, ORR was 59%. Median PFS 10.1 months. References: 10.1200/JCO.2021.39.15_suppl.5504

New Imatinib in Adenoid cystic carcinoma with KIT Protein expression: 4

Case reports of response. References: 15350030

New Imatinib in Adenoid cystic carcinoma with KIT Overexpression: R2

Phase II consortium-based study. N=15. ORR 0%. References: 15659505

New Imatinib in Adenoid cystic carcinoma with KIT Protein expression, Overexpression: R2

Phase 2. N=10. In patients with c-Kit advanced adenoid cystic carcinoma of the salivary gland, there was no responder to imatinib. Two patients had stable disease. References: 16757202

Changed Sapanisertib + Metformin in Solid tumours with AKT1 Oncogenic mutations: 4

References changed: 10.1200/JCO.2021.39.15_suppl.301710.1200/JCO.2021.39.15_suppl.3009.

Changed Sapanisertib + Metformin in Solid tumours with AKT2 Oncogenic mutations: 4

References changed: 10.1200/JCO.2021.39.15_suppl.301710.1200/JCO.2021.39.15_suppl.3009.

Changed Imatinib in Adenoid cystic carcinoma with KIT Overexpression: 4

Comments changed: Mixed results in one case series (one responder of 8).Mixed results in one case series (one responder of 8), but no response in a separate Phase II consortium study (N=15). References changed: 16135502, 15659505.

Changed Sapanisertib + Metformin in Solid tumours with MTORC1 Oncogenic mutations: 4

References changed: 10.1200/JCO.2021.39.15_suppl.301710.1200/JCO.2021.39.15_suppl.3009.

Changed Sapanisertib + Metformin in Solid tumours with PIK3CA Oncogenic mutations: 4

References changed: 10.1200/JCO.2021.39.15_suppl.301710.1200/JCO.2021.39.15_suppl.3009.

Changed Sapanisertib + Metformin in Solid tumours with PTEN Loss-of-function mutations: 4

References changed: 10.1200/JCO.2021.39.15_suppl.301710.1200/JCO.2021.39.15_suppl.3009.

Monday, 28 June 2021 (Version: 20210628AU)

New Ceralasertib + Olaparib in Ovarian cancer with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 3

Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13). References: 10.1200/JCO.2021.39.15_suppl.5516

New Ceralasertib + Olaparib in Ovarian cancer with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 3

Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13). References: 10.1200/JCO.2021.39.15_suppl.5516

New Ceralasertib + Olaparib in Ovarian cancer with Homologous Recombination Deficiency Score High: 3

Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13). References: 10.1200/JCO.2021.39.15_suppl.5516

New Tepotinib in Non-small cell lung cancer with MET Amplification: 3

Phase II VISION Cohort B. N=24. MET gene copy number >=2.5 by liquid biopsy. No exon 14 skipping mutations. ORR 42%. References: 10.1200/JCO.2021.39.15_suppl.9021

Sunday, 27 June 2021 (Version: 20210627AU)

New CB-103 in Adenoid cystic carcinoma with NOTCH1 Oncogenic mutations, Alterations: 4

Phase 1. NCT03422679. First-in-class CSL-NICD transcription factor complex inhibitor. SD as best response observed in 10 ACC patients (8 with NOTCH alterations). Two case of adenoid cystic carcinoma had prolonged disease control. References: 10.1200/JCO.2021.39.15_suppl.3020

Friday, 25 June 2021 (Version: 20210625AU)

New Afatinib in Pancreatic adenocarcinoma with NRG1 Fusions, ATP1B1-NRG1 fusion: 4

References: 31068372

New Adagrasib in Solid tumours with ALK EML4-ALK fusion: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with BRAF V600E, AKAP9-BRAF fusion: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with EGFR A289V: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with FGFR3 FGFR3-TACC3 fusion: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with KRAS G12C AND Amplification, G12D, G12R, G12V, G12W, G13D, Q61H, R68S, H95D, H95Q, H95R, Y96C: R2

Phase 1/2 KRYSTAL-1: on-target acquired resistance identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Sotorasib in Solid tumours with KRAS V8L, G13D, V14L, K16T, A59S, Q61R, R68S, G77V, Y96D, Y96C, K117N, D119H, A146P: R2

On-target resistance identified by deep mutational scanning and in vitro validated. References: 34161704

New Adagrasib in Solid tumours with KRAS V9F, G13D, V14L, K16T, A59S, Q61R, E62D, Y64N, R68S, M72L, G77V, H95D, H95Q, H95R, Y96D, Y96C, Q99K, K117N, D119H, A146P: R2

On-target resistance identified by deep mutational scanning and in vitro validated. References: 34161704

New Adagrasib in Solid tumours with MAP2K1 K57T, I99_K104del, E102_I103del: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with MET Amplification: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Pembrolizumab in High-grade gliomas, Anaplastic astrocytoma, Glioblastoma with Mismatch repair Deficient: R2

N=13. ORR 0%. All patients were microsatellite stable. References: 32823925

New Adagrasib in Solid tumours with NF1 R2637*: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with NRAS Q61K: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with PIK3CA H1047R: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with PIK3R1 S361fs: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with PTEN N48K, G209V: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with RAF1 RAF1-CCDC176 fusion, RAF1-TRAK1 fusion, Fusions: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with RET CCD6-RET fusion: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with RET M918T: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

New Adagrasib in Solid tumours with RIT1 P128L: R2

Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. References: 34161704

Changed Lutetium-177-PSMA-617 in Prostate cancer with PSMA Protein expression: 2

References changed: 34161051, 10.1200/JCO.2021.39.15_suppl.LBA4.

Changed Selinexor with XPO1 C528S: R2

Cancer type(s) changed: Chronic myelogenous leukaemia, Acute lymphoblastic leukaemia, Acute promyelocytic leukaemiaChronic myelogenous leukaemia, Acute lymphoblastic leukaemia, Acute promyelocytic leukaemia

Wednesday, 23 June 2021 (Version: 20210623AU)

New Pembrolizumab in Thymic carcinoma with CD274 Protein expression: 4

Phase 2. High PD-L1 expression is significantly correlating to responders in post hoc analysis. PD-L1 was positive if TPS >= 50%. Median PFS was longer in PD-L1 High group 24 v 9 months (PD-L1 low group). References: 29395863

New AZD8055, AZD8055 + Trametinib, AZD8055 + JQ1, JQ1, Trametinib in Thyroid cancer with EIF1AX A113_splice, N-terminal tail mutation, G6_splice, G8V, G9, K10N, R13, G15D: 4

Cell line model showing mutations in EIF1AX cooperate with RAS via ATF4/c-MYC and generates vulnerability to mTOR kinase inhibitors. References: 30305285

New AZD8055, AZD8055 + Trametinib, AZD8055 + JQ1, JQ1, Trametinib in Thyroid cancer with EIF1AX+NRAS EIF1AX:Oncogenic mutations and NRAS:Oncogenic mutations; EIF1AX:A113splice and NRAS:Oncogenic mutations: 4

Cell line model showing mutations in EIF1AX cooperate with RAS via ATF4/c-MYC and generates vulnerability to mTOR kinase inhibitors. References: 30305285

New Trastuzumab, Pertuzumab, Afatinib, Neratinib, Lapatinib in Solid tumours with ERBB2 V659E, G660D, G660R, R678Q, V697L, Q709, Transmembrane domain mutation, Juxtamembrane domain mutation: 4

Transmembrane and juxtamembrane domain mutations. References: 30449325

Tuesday, 22 June 2021 (Version: 20210622AU)

New HB-201, HB-201 + HB-202 in HPV16-positive cancers with HPV genotype HPV16-positive: 4

NCT04180215. References: 10.1200/JCO.2021.39.15_suppl.2502

Changed Abemaciclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: TGA approved. PBS reimbursed. MONARCH-2TGA approved. Not PBS reimbursed. MONARCH-2.

Changed Palbociclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: TGA approved. PBS reimbursed. PALOMA-3TGA approved. Not PBS reimbursed. PALOMA-3.

Changed Ribociclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: TGA approved. PBS reimbursed. MONALEESA-3TGA approved. Not PBS reimbursed. MONALEESA-3.

Changed Imatinib in Dermatofibrosarcoma protuberans with PDGFB COL1A1-PDGFB Fusion: 1

Comments changed: TGA approved. PBS reimbursedTGA approved. Not PBS reimbursed.

Changed Imatinib in Chronic eosinophilic leukaemia with PDGFRA FIP1L1-PDGFRA Fusion; Fusion: 1

Comments changed: TGA approved. PBS reimbursedTGA approved. Not PBS reimbursed.

Changed Encorafenib + Cetuximab in Colorectal cancer with BRAF V600E: 1B

Comments changed: Not TGA approved. FDA approved. OS for E+C doublet 9.3 months. ORR 26.8%..

Changed Olaparib in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 1B

Comments changed: Not TGA approved. POLO trial..

Changed Pembrolizumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with CD274 Protein expression: 3

Comments changed: Not TGA approved. KEYNOTE-059: Phase 2 single arm study in previously treated disease (third-line and beyond). ORR: 16% in PD-L1 positive group (defined as CPS >= 1%, 22C3 pharmDx assay). DOR: 16.3 months. FDA accelerated approval in 2017, but reviewed 2021 due to low response rate and negative confirmatory trial KEYNOTE-061.Not TGA approved. KEYNOTE-059: Phase 2 single arm study in previously treated disease (third-line and beyond). ORR 16% in PD-L1 positivity (defined as CPS >= 1%, 22C3 pharmDx assay). DOR: 16.3 months. FDA accelerated approval in 2017, but reviewed 2021 due to low response rate and negative confirmatory trial KEYNOTE-061..

Changed Trastuzumab + Pertuzumab in Colorectal cancer with ERBB2 Amplification: 3

Comments changed: Phase 2 Basket trial. MyPathway. Colorectal cohort. ORR: 32% (18/57).Phase 2 Basket trial. MyPathway. Colorectal cohort. ORR 18 / 57 patients (32%)..

Changed Savolitinib in Papillary renal cell carcinoma with MET Oncogenic mutations, Amplification: 3

Comments changed: Type 1 papillary renal cell carcinoma. Note: statistical significance for the primary endpoint, PFS, was not demonstrated in the phase 3 SAVOIR trial due to poor recruitment.Type 1 PRCC. SAVOIR, NS P3 study due to by recruitment..

Changed Dostarlimab in Solid tumours with Mismatch repair Deficient: 3

Comments changed: GARNET: ORR 39% in dMMR patients across tumour types. Note: no responses seen in 4 pancreatic cancer cases.GARNET: ORR 39% in dMMR patients across tumour types. Note no response seen in 4 pancreatic cancer cases..

Changed BOS172738 in Medullary thyroid cancer with RET Fusions: 3

Comments changed: ORR 44% (7/16), including 1 CRORR 7/16 (44%), including 1 CR.

Changed BOS172738 in Non-small cell lung cancer with RET Fusions: 3

Comments changed: ORR 33% (10/30)ORR 10/30 (33%).

Changed Vandetanib in Non-small cell lung cancer with RET Fusions: 3

Comments changed: Single-arm phase 2. LURET. ORR 47%. PFS 4.7moLURET. Single-arm phase 2. ORR 47%. PFS 4.7mo.

Changed Belvarafenib in Solid tumours with ARAF K336M, K336M and G387D, R362H and G387D: 4

Comments changed: K336M is a kinase-dead mutation but remains sensitive to belvarafenibK336M is a kinase dead mutation but remains sensitive to belvarafenib.

Changed Dasatinib in Ovarian Clear Cell Carcinoma with ARID1A Oncogenic mutations: 4

Comments changed: Dasatinib inhibits YES1, which is addicted in ARID1A-deficient tumoursDasatinib inhibits YES1, which is addicted in ARID1A deficient tumours.

Changed BAY-1895344 in Solid tumours with ATM Loss of protein expression; Loss-of-function mutations: 4

Comments changed: Phase 1 study of BAY-1895344. 4 of 11 patients with ATM protein loss or loss-of-function mutations had objective response in appendiceal, endometrial, breast, and urothelial carcinomas. SD was seen in 8 patients.Phase 1 study of BAY-1895344. 4 of 11 patients with ATM protein loss or loss of function mutations had objective response in appendiceal, endometrial, breast, and urothelial carcinomas. SD was seen in 8 patients..

Changed Afatinib in Non-small cell lung cancer with EGFR Amplification AND NOT Oncogenic mutations: 4

Comments changed: . ORR of 4/43 (9%) in the EGFR FISH-positive subgroup (gene/chr ratio >= 2, or Copy number >= 15) without EGFR sensitising mutation..

Changed Debio1347 in Solid tumours with FGFR1 Fusion: 4

Comments changed: Cholangiocarcinoma: 2 PR. CRC: 1PR2 PR Cholangiocarcinoma; 1PR CRC.

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours except Colorectal cancer with Tumour Mutational Burden High

Tier changed: 43. Comments changed: MSS with High TMB Benefit from IO: However this is a retrospective, hypothesis seeking study. 4 is more appropriate than 3 unless prospective trials.

Changed Larotrectinib in Solid tumours with NTRK1 Alterations AND NOT fusion: R2

Comments changed: One PR (of 73) with short DOR.One of 73 patient with short PR with short direction..

Changed Larotrectinib in Solid tumours with NTRK2 Alterations AND NOT fusion: R2

Comments changed: One PR (of 73) with short DOR.One of 73 patient with short PR with short direction..

Changed Larotrectinib in Solid tumours with NTRK3 Alterations AND NOT fusion: R2

Comments changed: One PR (of 73) with short DOR.One of 73 patient with short PR with short direction..

Monday, 21 June 2021 (Version: 20210621AU)

New Regorafenib in Gastrointestinal stromal tumour with KIT Protein expression: 1B

PBS reimbursed based on CD117 (c-KIT) IHC. NCCN Category 1. References: 23177515

New Lutetium-177-PSMA-617 in Prostate cancer with PSMA Protein expression: 2

Phase 3. VISION. N=831. PSMA-positive metastatic lesion defined as Gallium-68 positive. Median OS: 15.3 v 11.3 months (HR: 0.62). Radiological PFS: HR 0.40. 8.7 v 3.4 months. References: 10.1200/JCO.2021.39.15_suppl.LBA4

New PDS0101 + M9241 + Bintrafusp alpha in HPV16-positive cancers, Cervical cancer, Anal cancer, Head and neck squamous cell carcinoma, Vulvar cancer, Vaginal cancer with HPV genotype HPV16-positive: 3

NCT04287868. ORR 56%. ORR 42% (N=5/12) in checkpoint inhibitor refractory disease. HPV16 genotyping determined by PCR-based assay. References: 10.1200/JCO.2021.39.15_suppl.2501

Removed Ibrutinib in Non-Hodgkin’s lymphoma with CD20 alterations Protein expression: Tier 1B

Changed Binimetinib + Encorafenib in Melanoma with BRAF V600E, V600K

Tier changed: 1B. Comments changed: TGA approaved. PBS reimbursed. COLOMBUS trial.Encorafenib is not PBS reimbursed. COLOMBUS trial..

Changed Olaparib + Bevacizumab in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations, Oncogenic mutations (germline)

Tier changed: 12. Comments changed: Combination not TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX..

Changed Olaparib + Bevacizumab in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations, Oncogenic mutations (germline)

Tier changed: 12. Comments changed: Combination not TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX..

Changed Ibrutinib in Mantle cell lymphoma with CD20 Protein expression: 1

References changed: 23782157, 23782157.

Changed Daratumumab + Bortezomib + Dexamethasone in Multiple myeloma with CD38 Overexpression

Tier changed: 1B.

Changed Fulvestrant in Breast cancer with ESR1 Protein expression

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursedTGA approved. Not PBS reimbursed.

Changed Abemaciclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression

Tier changed: 1B.

Changed Palbociclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression

Tier changed: 1B.

Changed Ribociclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression

Tier changed: 1B.

Changed Therapy in Gastrointestinal stromal tumour with KIT Protein expression: 1

Therapy changed: Imatinib, Sunitinib, Regorafenib. References changed: 12181401, 17046465, 23177515.

Changed Imatinib in Dermatofibrosarcoma protuberans with PDGFB COL1A1-PDGFB Fusion

Tier changed: 1B.

Changed Imatinib in Chronic eosinophilic leukaemia with PDGFRA FIP1L1-PDGFRA Fusion; Fusion

Tier changed: 1B.

Changed Encorafenib + Cetuximab in Colorectal cancer with BRAF V600E

Tier changed: 1B2.

Changed Olaparib in Prostate cancer with BRCA1 Oncogenic mutations

Tier changed: 1B2. Comments changed: TGA Approved. Not PBS reimbursed. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). FoundationOne CdxNot TGA Approved. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). FoundationOne Cdx.

Changed Olaparib in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline)

Tier changed: 1B2.

Changed Olaparib in Prostate cancer with BRCA2 Oncogenic mutations

Tier changed: 1B2. Comments changed: TGA Approved. Not PBS reimbursed. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control).Not TGA Approved. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control)..

Changed Vemurafenib in Erdheim-Chester disease with BRAF V600E

Tier changed: 21B.

Changed Ofatumumab in Chronic lymphocytic leukaemia with CD20 Protein expression

Tier changed: 21B.

Changed Therapy in Prostate cancer with PSMA Protein expression: 3

Therapy changed: Lutetium-177-PSMA-617177Lu-PSMA radioconjugate. Comments changed: Phase 2. PSARR: 66% v Cabazitaxel.

Changed Vismodegib in Basal cell carcinoma with PTCH1 Truncating mutations: 3

Comments changed: STEVIE trial. The drug is TGA-approved but not selected by PTCH1 mutation..

Friday, 18 June 2021 (Version: 20210618AU)

New Sapanisertib + Metformin in Solid tumours with AKT1 Oncogenic mutations: 4

References: 10.1200/JCO.2021.39.15_suppl.3009

New Sapanisertib + Metformin in Solid tumours with AKT2 Oncogenic mutations: 4

References: 10.1200/JCO.2021.39.15_suppl.3009

New BI907828 in Dedifferentiated liposarcoma with MDM2 Amplification: 4

References: 10.1200/JCO.2021.39.15_suppl.3016

New Sapanisertib + Metformin in Solid tumours with MTORC1 Oncogenic mutations: 4

References: 10.1200/JCO.2021.39.15_suppl.3009

New Sapanisertib + Metformin in Solid tumours with PIK3CA Oncogenic mutations: 4

References: 10.1200/JCO.2021.39.15_suppl.3009

New Sapanisertib + Metformin in Solid tumours with PTEN Loss-of-function mutations: 4

References: 10.1200/JCO.2021.39.15_suppl.3009

Changed Avapritinib in Mastocytosis with KIT D816V

Tier changed: 23. Comments changed: Not TGA approved. FDA approved 16/6/2021 based on EXPLORER (NCT02561988) and PATHFINDER (NCT03580655) data..

Wednesday, 16 June 2021 (Version: 20210616AU)

New Pralsetinib in Medullary thyroid cancer, Thyroid cancer with RET Oncogenic mutations and NOT Amplification, M918T, V804L, V804M, Cysteine rich domain mutation: 2

Not TGA approved. FDA approved. Phase 2 ARROW. ORR 60% (33/55) in previously-treated MTC, 71% (15/21) treatment-naive MTC, and 89% (8/9) other RET-altered thyroid cancers. References: 34118198, 10.1200/JCO.2019.37.15_suppl.6018

New Famitinib + Camrelizumab + Nab-paclitaxel in Triple-negative breast cancer with Tumour microenvironment Immunomodulatory subtype: 3

Phase 2. FUTURE-C-PLUS. N=46: The immunomodulatory (IM) subtype is defined by CD8+ IHC in tumour >= 10%. ORR: 81% in patient (39/48 in ITT population). References: 10.1200/JCO.2021.39.15_suppl.1007

New Atezolizumab + Nab-paclitaxel in Triple-negative breast cancer with Molecular subtype BLIA molecular subtype: 4

Retrospective analysis from IMpassion130. BLIA molecular subtypes showed both improved PFS and OS in PD-L1 IC-positive subgroup. Molecular subtypes assessed using Burstein classification. References: 10.1200/JCO.2021.39.15_suppl.1006

New Atezolizumab + Nab-paclitaxel in Triple-negative breast cancer with Tumour microenvironment Inflamed immune phenotype: 4

Retrospective analysis from IMpassion130. Inflammed immune phenotype showed both improved PFS and OS in PD-L1 IC-positive subgroup. References: 10.1200/JCO.2021.39.15_suppl.1006

New Venetoclax + Fulvestrant in Breast cancer with ESR1 Protein expression: R2

Phase 2 VERONICA. N=103. ER-positive, HER2-negative locally advanced or metastatic breast cancer treated with prior CDK4/6i. CBR at 24 weeks: 12 (Venetoclax + Fulvestrant) vs 14% (Fulvestrant alone). ORR 4%. References: 10.1200/JCO.2021.39.15_suppl.1004

New Lapatinib, Neratinib, Tucatinib, Trastuzumab in Breast cancer with ERBB2 L755S: R2

HER2+ BT474 cell model study. References: 10.1158/1538-7445.SABCS20-PD3-09

New Ado-Trastuzumab Emtansine, Poziotinib in Breast cancer with ERBB2 L755S: 4

HER2+ BT474 cell model study. References: 10.1158/1538-7445.SABCS20-PD3-09

Removed Pralsetinib in Medullary thyroid cancer with RET alterations Oncogenic mutations and NOT Amplification: Tier 2

Changed Pralsetinib in Non-small cell lung cancer with RET : 2

Alterations changed: Fusions, CCDC6-RET fusion, KIF5B-RET fusion. Comments changed: Not TGA approved. FDA approved. ARROW. ORR 61% (53/87) with DCR 91% (79/87) in previous platinum group.Not TGA approved. FDA approved. ARROW. ORR 65%. DCR 93%. References changed: 34118197, 10.1200/JCO.2019.37.15_suppl.9008; 10.1200/JCO.2020.38.15_suppl.9515.

Tuesday, 15 June 2021 (Version: 20210615AU)

New Durvalumab + Savolitinib in Papillary renal cell carcinoma with MET Alteration, Amplification, Oncogenic mutations: 3

Phase 2 CALYPSO: MET-driven PRCC. ORR 57% (8/14). References: 10.1200/JCO.2021.39.15_suppl.4511

New Durvalumab + Savolitinib in Papillary renal cell carcinoma with HGF Amplification: 3

Phase 2 CALYPSO: MET-driven PRCC. ORR 57% (8/14). References: 10.1200/JCO.2021.39.15_suppl.4511

Changed TK216 + Vincristine in Ewing sarcoma with FLI1 EWSR1-FLI1 Fusion: 4

Comments changed: Phase 1 and 2: NCT02657005: ORR 7% (3/31 with 2 CR) and CBR 45% (14/31) in the dose expansion cohort at RP2D. mPFS 1.9 months.CBR 62%. References changed: 10.1200/JCO.2021.39.15_suppl.11500, 10.1016/j.annonc.2020.08.1846NCT02657005, 10.1016/j.annonc.2020.08.1846.

Thursday, 10 June 2021 (Version: 20210610AU)

New Amivantamab + Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 3

Phase 1 CHRYSALIS. Combination treatment after osimertinib relapse. Dose expansion N=45. ORR 36%. References: 10.1200/JCO.2021.39.15_suppl.9006

New Mobocertinib in Non-small cell lung cancer with EGFR Exon 20 insertion, A763_Y764insFQEA, V769_D770insGG, V769_D770insASV, D770_N771insG, D770_N771insGL, D770_N771insGD, D770delinsGY, N771delinsKH, N771_P772insH, P772_H773insPNP, H773_V774insNPH, V774_C775insHV: 3

Combined PPP and EXCLAIM cohort. References: 10.1200/JCO.2021.39.15_suppl.9014

New Amivantamab + Lazertinib in Non-small cell lung cancer with EGFR+EGFR C797S and Exon 19 deletion, C797S and L858R, L718 and Exon 19 deletion, L718 and L858R, G724S and Exon 19 deletion, G724S and L858R, L792H and Exon 19 deletion, L792H and L858R, G796S and Exon 19 deletion, G796S and L858R, E709K and Exon 19 deletion, E709K and L858R, Amplification and Exon 19 deletion, Amplification and L858R: 3

Phase 1 CHRYSALIS. Combination treatment after osimertinib relapse. Dose expansion N=45. ORR 36%. The ORR in 17/45 (47%) with EGFR or MET-based resistance mechanism identified by NGS. References: 10.1200/JCO.2021.39.15_suppl.9006

New Amivantamab + Lazertinib in Non-small cell lung cancer with EGFR+MET EGFR:Exon 19 deletion and MET:amplification, EGFR:L858R and MET:amplification, EGFR:Exon 19 deletion and MET:exon 14 skipping mutation, EGFR:L858R and MET:exon 14 skipping mutation: 3

Phase 1 CHRYSALIS. Combination treatment after osimertinib relapse. Dose expansion N=45. ORR 36%. The ORR in 17/45 (47%) with EGFR or MET-based resistance mechanism identified by NGS. References: 10.1200/JCO.2021.39.15_suppl.9006

New Trastuzumab + Pertuzumab + Docetaxel in Non-small cell lung cancer with ERBB2 Exon 20 insertion, Exon 20 mutation: 3

Phase 2 IFCT-1703 R2D2. ORR 29% (13/45) in patients treated with at least one prior line of therapy. References: 10.1200/JCO.2021.39.15_suppl.9015

New Amivantamab + Lazertinib in Non-small cell lung cancer with MET Overexpression: 3

Phase 1 CHRYSALIS. ORR 90% (9 in 10) in patients with IHC positive (defined as combined EGFR+MET H score >= 400). References: 10.1200/JCO.2021.39.15_suppl.9006

New Sotorasib in Non-small cell lung cancer with KEAP1+KRAS KRAS:G12C AND NOT KEAP1:Oncogenic mutations: 4

Higher ORR (44%) was identified in patients with KEAP oncogenic mutations treated with Sotorasib in the CodeBreak100 trial. References: 34096690, 10.1200/JCO.2021.39.15_suppl.9003

New Rucaparib in Non-small cell lung cancer with BRCA1 Oncogenic mutations: R2

Phase 2 Lung-MAP Sub-Study, S1900A. ORR 7%. In BRCA1/2 cohort, ORR 13%. References: 10.1200/JCO.2021.39.15_suppl.9024

New Rucaparib in Non-small cell lung cancer with BRCA2 Oncogenic mutations: R2

Phase 2 Lung-MAP Sub-Study, S1900A. ORR 7%. In BRCA1/2 cohort, ORR 13%. References: 10.1200/JCO.2021.39.15_suppl.9024

New Fulvestrant + Palbociclib in Breast cancer with CCNE1 mRNA expression: R2

Exploratory analysis from Phase III PEARL study: high tumour CCNE mRNA expression is correlated to relevance. References: 10.1200/JCO.2021.39.15_suppl.1014

New Rucaparib in Non-small cell lung cancer with Loss-of-heterozygosity score High: R2

Phase 2 Lung-MAP Sub-Study, S1900A. ORR 7%. Genomic LOH does not predict activity. References: 10.1200/JCO.2021.39.15_suppl.9024

New Amivantamab + Lazertinib in Non-small cell lung cancer with MET No protein expression: R2

Phase 1 CHRYSALIS. ORR 10% (1 in 10 patients) with negative IHC (defined as combined EGFR+MET H score < 400). References: 10.1200/JCO.2021.39.15_suppl.9006

New Trametinib in Epithelioid hemangioendothelioma with CAMTA1 TAZ-CAMTA1 fusion: R2

Phase 2 P10015/SARC033: ORR 0% (0/26) in patients with EHE habouring TAZ-CAMTA1 fusion treated with trametinib. However, 40% patient had SD > 6 months. References: 10.1200/JCO.2021.39.15_suppl.11503

Changed Sotorasib in Non-small cell lung cancer with KRAS G12C: 2

References changed: 32955176, 34096690, 10.1016/j.jtho.2019.09.020, 10.1200/JCO.2021.39.15_suppl.900332955176, 10.1016/j.jtho.2019.09.020.

Wednesday, 9 June 2021 (Version: 20210609AU)

New Nab-sirolimus in Solid tumours with TSC1 Oncogenic mutations: 4

Case series. References: 10.1200/JCO.2021.39.15_suppl.3111

New Nab-sirolimus in Solid tumours with TSC2 Oncogenic mutations: 4

Case series. References: 10.1200/JCO.2021.39.15_suppl.3111

New Olaparib, PDD00017273 in Breast cancer with BRCA1 Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib, PDD00017273 in Breast cancer with BRCA2 Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib in Breast cancer with PALB2 Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib in Breast cancer with RAD51C Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib, PDD00017273 in Breast cancer with BARD1 Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib, PDD00017273 in Breast cancer with MRE11A Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib in Breast cancer with RAD50 Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib, PDD00017273 in Breast cancer with FAM175A Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib in Breast cancer with ATM Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

New Olaparib in Breast cancer with XRCC2 Loss-of-function mutations: 4

Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. References: 28254358

Tuesday, 8 June 2021 (Version: 20210608AU)

New DZD9008 in Non-small cell lung cancer with EGFR Exon 20 insertion, V769_D770insASV, D770_N771insG, D770_N771insSVD, D770delinsDV, N771_P772insSVDN, H773_V774insH, H773_V774insAH, H773_V774insPHPH, V774_C775insHV: 3

Phase 1 WU-KONG1/2 trials. At the RP2D dose, ORR 48% (15/31). DCR 90% (28/31). References: 10.1200/JCO.2021.39.15_suppl.9008

New Patritumab Deruxtecan in Non-small cell lung cancer with EGFR Oncogenic mutations, Exon 20 insertions, Exon 19 deletions, G719, G724S, G719Y, T790M, C797S, L858R, L861Q: 3

Phase 1. Efficacy population (N=57). ORR 39% (22/57). DCR 72%. Median DCR 6.9 months. Similar efficacy seen in prior Osimertinib population. ORR 32% (8/25) in patients with brain metastasis. Response not dependent on HER3 membrane H-scores. References: 10.1200/JCO.2021.39.15_suppl.9007

New Belvarafenib in Solid tumours with ARAF K336M, K336M and G387D, R362H and G387D: 4

K336M is a kinase dead mutation but remains sensitive to belvarafenib. References: 33953400

New Belvarafenib in Melanoma, Colorectal cancer with BRAF V600E: 4

NCT02405065, NCT03118817. References: 33953400

New Belvarafenib in Melanoma with NRAS Q61R, Q61S: 4

NCT02405065, NCT03118817. References: 33953400

New Afatinib in Non-small cell lung cancer with NRG1 Fusions: 4

Retrospective registry-based study. Afatinib ORR 25%. CD74-NRG1 and non-CD74-NRG1 have similar ORR (22% and 27% respectively). References: 34077268

New Belvarafenib in Solid tumours with ARAF G377R, G387D, G387R, G387S, P462L, Overexpression: R2

Activating ARAF mutation propagates MAPK signaling through dimer- and a kinase activity-dependent mechanism, bypassing inhibition of RAF dimer inhibition. References: 33953400

New Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2 No protein expression, Low protein expression: R2

Phase 2 DESTINY-CRC01. No objective responses seen in cohort B (IHC2+ and ISH-negative) or cohort C (IHC1+). References: 33961795, 10.1200/JCO.2020.38.15_suppl.4000

New Defactinib in Solid tumours with NF2 Loss-of-function mutations: R2

NCI-MATCH Arm U: ORR 3% (1/31) with the only responder in choroid meningioma. PFS 1.3 months. NCT04439331. References: 10.1200/JCO.2021.39.15_suppl.3087

New Binimetinib in Solid tumours except melanoma with NRAS G12, G13, Q61: R2

NCI-MATCH. NRAS subprotocol. ORR 2% with a single responder. References: 33637626

New Pembrolizumab + Carboplatin + Pemetrexed in Non-small cell lung cancer with NRG1 Fusions: R2

Retrospective registry-based study. Chemoimmunotherapy ORR 0%. References: 34077268

New Vemurafenib + Cobimetinib in Langerhans cell sarcoma with RASA1 Loss-of-function mutations: R2

References: 30977771

New Selinexor in Chronic myelogenous leukaemia, Acute lymphoblastic leukaemia, Acute promyelocytic leukaemia with XPO1 C528S: R2

References: 27634897

Removed Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2+KRAS alterations ERBB2:Overexpression and NOT KRAS:Oncogenic mutations: Tier 3

Changed Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2+KRAS : 3

Alterations changed: ERBB2:Amplification and ERBB2:Protein expression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E, ERBB2:Overexpression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600EERBB2:Amplification and NOT KRAS:Oncogenic mutations. Comments changed: Phase 2 DESTINY-CRC01. ORR 45% (24/53) in HER2-positive (Cohort A, IHC 3+ or IHC2+ and ISH-positive) population.. References changed: 33961795, 10.1200/JCO.2020.38.15_suppl.4000.

Monday, 7 June 2021 (Version: 20210607AU)

New AMG-650 in Solid tumours with TP53 Oncogenic mutations: 4

NCT04293094. References: 10.1200/JCO.2021.39.15_suppl.TPS5600

New Pamiparib in Breast cancer with BRCA1 Oncogenic mutations (germline): 3

Phase 2: NCT03575065. ORR 38% in TNBC and 62% in HR-positive germline BRCA mutated population. Median PFS 5.5 months (TNBC) and 9.2 months (HR-positive) respectively. References: 10.1200/JCO.2021.39.15_suppl.1087

New Pamiparib in Breast cancer with BRCA2 Oncogenic mutations (germline): 3

Phase 2: NCT03575065. ORR 38% in TNBC and 62% in HR-positive germline BRCA mutated population. Median PFS 5.5 months (TNBC) and 9.2 months (HR-positive) respectively. References: 10.1200/JCO.2021.39.15_suppl.1087

New Giredestrant in Breast cancer with ESR1 Protein expression: 4

NCT03332797. References: 10.1200/JCO.2021.39.15_suppl.1017

New H3B-6545 in Breast cancer with ESR1 Protein expression, Y537S: 4

Phase 1/2: ORR 17% (12/72) at RP2D in heavily pretreated patients and visceral metastases. 7/10 PR and SD seen in clonal Y537S mutation. References: 10.1200/JCO.2021.39.15_suppl.1018

New H3B-6545 in Breast cancer with ESR1 D538G: R2

Phase 1/2: ORR 17% (12/72) at RP2D in heavily pretreated patients and visceral metastases, but ORR 0% (0/17) responses seen in D538G. References: 10.1200/JCO.2021.39.15_suppl.1018

New Proxalutamide in Breast cancer with AR Protein expression: 3

Phase 1B: NCT04103853. AR positivity defined as >1% IHC. References: 10.1200/JCO.2021.39.15_suppl.1019

New Enobosarm in Breast cancer with AR+ESR1 AR:Protein expression and ESR1:Protein expression: 3

AR positivity is defined as percentage of IHC positive cells. Postmenopausal women ER positive. CBR at 24 weeks. 32% in 9mg cohort. 29% in 18mg cohort. % nuclei staining correlates with ORR and CBR. References: 10.1200/JCO.2021.39.15_suppl.1020

New RC48-ADC in Breast cancer with ERBB2 Amplification, Overexpression, Protein expression, Low protein expression: 3

Pooled analysis of two phase 1 studies. ORR at 2mg/kg: 43% HER2-positive, 40% in HER2-2+, and 31% in HER2 IHC 1+. References: 10.1200/JCO.2021.39.15_suppl.1022

New Durvalumab + Paclitaxel + Trastuzumab deruxtecan in Triple-negative breast cancer with ERBB2 Protein expression, Low protein expression: 4

BEGONIA Arm 6: Confirmed ORR 4/4. Ongoing enrollment. NCT03742102. References: 10.1200/JCO.2021.39.15_suppl.1023

Changed Therapy in Renal cell carcinoma with VHL Oncogenic mutations (germline): 3

Therapy changed: BelzutifanMK-6482.

Sunday, 6 June 2021 (Version: 20210606AU)

New Trastuzumab + Capecitabine + Oxaliplatin in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification: 1

TGA approved. PBS reimbursed. Three Phase 2 trials. Ryu et al, HEROX, and CGOG1001. HER2 positivity was defined as IHC 3+ or FISH-positive in all three studies. References: 25661103, 30927036, 26857702

New Pembrolizumab + Trastuzumab + Cisplatin + Fluorouracil, Pembrolizumab + Trastuzumab + Capecitabine + Oxaliplatin in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification: 3

Phase 3: KEYNOTE-811 (NCT03615326). First interim analysis. ORR 74% for pembro + SOC vs 52% for SOC alone. DOR 10.6 vs 9.5mo. PFS and OS are not yet mature. References: 10.1200/JCO.2021.39.15_suppl.4013

New Selumetinib in Solid tumours with BRAF V600E: R2

Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed. References: 10.1200/JCO.2021.39.15_suppl.10008

New Selumetinib in Solid tumours with HRAS Oncogenic mutations: R2

Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed. References: 10.1200/JCO.2021.39.15_suppl.10008

New Selumetinib in Solid tumours with KRAS Oncogenic mutations: R2

Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed. References: 10.1200/JCO.2021.39.15_suppl.10008

New Selumetinib in Solid tumours with NRAS Oncogenic mutations: R2

Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed. References: 10.1200/JCO.2021.39.15_suppl.10008

Changed Entrectinib in Solid tumours with NTRK1 : 1B

Alterations changed: Fusions, CD74-NTRK1 fusion, CDC42BPA-NTRK1 fusion, CGN-NTRK1 fusion, EPS15L1-NTRK1 fusion, ERC1-NTRK1 fusion, LMNA-NTRK1 fusion, PDIA3-NTRK1 fusion, PEAR1- NTRK1 fusion, PLEKHA6-NTRK1 fusion, SQSTM1-NTRK1 fusion, TPM3-NTRK1 fusion, TPR-NTRK1 fusion, TRIM33-NTRK1 fusionFusions, CD74-NTRK1 fusion, CDC42BPA-NTRK1 fusion, CGN-NTRK1 fusion, EPS15L1-NTRK1 fusion, ERC1-NTRK1 fusion, LMNA-NTRK1 fusion, PDIA3-NTRK1 fusion, PEAR1- NTRK1 fusion, PLEKHA6-NTRK1 fusion, SQSTM1-NTRK1 fusion, TPM3-NTRK1 fusion, TPR-NTRK1 fusion, TRIM33- NTRK1 fusion.

Changed Sotorasib in Non-small cell lung cancer with KRAS G12C: 2

Comments changed: Not TGA approved. FDA approved for second-line and beyond. Phase 2 CODEBREAK100. Previously treated patients. ORR 37%. PFS 6.8mo. OS 12.5mo.Not TGA approved. FDA approved for second-line and beyond. CODEBREAK 100 ORR 32.2%.

Saturday, 5 June 2021 (Version: 20210605AU)

New Trastuzumab + Pertuzumab in Solid tumours with ERBB2 Amplification, Oncogenic mutations, Overexpression: 3

Phase 2 Basket trial. MyPathway. N=258. ORR 60/258 (23%). ORR in KRAS-wild type: 26%. HER2 status determined by local testing (FISH HER2/Chr17 ratio > 2.0 or HER2 CN > 6.0 or IHC 3+). References: 10.1200/JCO.2021.39.15_suppl.3004

New Belvarafenib + Cobimetinib in Melanoma with NRAS Q61R, Q61K: 3

Phase 1 Dose expansion. ORR: 5/13 (38%) including patients with prior exposure. Median PFS 7.3 mo. However, no responses seen in G12S. References: 10.1200/JCO.2021.39.15_suppl.3007

New Zenocutuzumab in Solid tumours with NRG1 Fusions, ATP1B1-NRG1 fusion, SLC3A2-NRG1 fusion, CD74-NRG1 fusion: 3

Phase 1/2 trial. N=51. Solid tumours including pancreatic adenocarcinoma, non-small cell lung cancer. ORR entire cohort 29%. ORR pancreatic cancer: 5/12 (42%) with durable analysis 100% CA19-9 reduction. ORR NSCLC 6/24 (25%). References: 10.1200/JCO.2021.39.15_suppl.3003

New BOS172738 in Medullary thyroid cancer with RET Fusions: 3

ORR 7/16 (44%), including 1 CR. References: 10.1200/JCO.2021.39.15_suppl.3008

New BOS172738 in Non-small cell lung cancer with RET Fusions: 3

ORR 10/30 (33%). References: 10.1200/JCO.2021.39.15_suppl.3008

New Trastuzumab + Pertuzumab in Solid tumours with ERBB2+KRAS ERBB2:Amplification AND KRAS:Oncogenic mutations; ERBB2:Oncogenic mutations AND KRAS:Oncogenic mutations; ERBB2:Overexpression AND KRAS:Oncogenic mutations: R2

Phase 2 Basket trial. MyPathway. ORR in KRAS-co-mutations: 1 / 26 (4%). References: 10.1200/JCO.2021.39.15_suppl.3004

Changed Trastuzumab + Pertuzumab in Colorectal cancer with ERBB2 Amplification: 3

Comments changed: Phase 2 Basket trial. MyPathway. Colorectal cohort. ORR 18 / 57 patients (32%)..

Changed Trastuzumab + Pertuzumab in Salivary gland cancers with ERBB2 : 3

Alterations changed: Amplification, OverexpressionAmplification; Overexpression.

Friday, 4 June 2021 (Version: 20210604AU)

New Vemurafenib + Cobimetinib in Papillary craniopharyngioma with BRAF V600E: 3

Phase II Alliance A071601. NCT03224767. Objective response in 15 of 16 patients. References: 10.1200/JCO.2021.39.15_suppl.2000

New Olaparib in High-grade gliomas, Anaplastic astrocytoma, Glioblastoma with IDH1 R132H, Oncogenic mutations: 3

Phase 2 OLAGLI. In heavily pretreated recurrent high-grade glioma, single-agent olaparib resulted in ORR 5% and CBR 31% at 6 months. DOR 9 months. References: 10.1200/JCO.2021.39.15_suppl.2007

Changed Medroxyprogesterone Acetate with PGR Protein expression: 1

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Changed Lenvatinib + Pembrolizumab with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: 1B

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Changed Ibrutinib with CXCR4 Oncogenic mutations: 2

Cancer type(s) changed: Waldenstroms macroglobulinaemiaWaldenstroms macroglobulinemia

Changed Dostarlimab with Microsatellite Instability High: 2

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Changed Dostarlimab with Mismatch repair Deficient: 2

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Changed Ibrutinib with MYD88 Oncogenic mutations, L265P: 2

Cancer type(s) changed: Waldenstroms macroglobulinaemiaWaldenstroms macroglobulinemia

Changed Tamoxifen + Medroxyprogesterone Acetate, Fulvestrant, Exemestane, Everolimus + Letrozole with ESR1 Protein expression: 3

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Changed Tipifarnib with HRAS Oncogenic mutations: 3

Cancer type(s) changed: Head and neck squamous cell carcinoma , Salivary gland cancers, Urothelial carcinomaHead and Neck Squamous Cell Carcinoma, Salivary Gland Cancers, Urothelial Carcinoma

Changed Letrozole, Anastrozole with ESR1 Protein expression: 4

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Changed Dovitinib with FGFR2 S252W, N549K, C382R, Oncogenic mutations: 4

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Changed Fadraciclib with MCL1 Amplification: 4

Cancer type(s) changed: Endometrial cancerEndometrial Carcinoma

Thursday, 3 June 2021 (Version: 20210603AU)

Changed Atezolizumab in Non-small cell lung cancer with CD274+EGFR+ALK : 1B

Alterations changed: CD274:Protein expression and NOT EGFR:Oncogenic mutations and NOT ALK:fusionCD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion.

Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with CD274+EGFR+ALK : 1B

Alterations changed: CD274:Protein expression and NOT EGFR:Oncogenic mutations and NOT ALK:fusionCD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion.

Changed Sorafenib in Gastrointestinal Stromal Tumour with KIT : 2

Alterations changed: Oncogenic mutations, V654A, T670I, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829POncogenic mutation, V654A, T670I, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P.

Changed Ipatasertib + Abiraterone in Prostate cancer with PTEN : 2

Alterations changed: Loss of protein expression; Loss-of-function mutations.

Changed Osimertinib + Savolitinib in Non-Small Cell Lung Cancer with EGFR+MET : 3

Alterations changed: EGFR:Oncogenic mutations and MET:amplificationEGFR:oncogenic mutation and MET:amplification.

Changed Fam-trastuzumab deruxtecan-nxki in Colorectal Cancer with ERBB2+KRAS : 3

Alterations changed: ERBB2:Amplification and NOT KRAS:Oncogenic mutations.

Changed Fam-trastuzumab deruxtecan-nxki in Colorectal Cancer with ERBB2+KRAS : 3

Alterations changed: ERBB2:Overexpression and NOT KRAS:Oncogenic mutations.

Changed Bevacizumab + erlotinib in Papillary Renal Cell Carcinoma with FH : 3

Alterations changed: Loss-of-function mutations (germline)Loss-of-function mutation (germline).

Changed Azacitidine + Venetoclax in Acute Myeloid Leukaemia with IDH1 : 3

Alterations changed: Oncogenic mutations.

Changed Azacitidine + Venetoclax in Acute Myeloid Leukaemia with IDH2 : 3

Alterations changed: Oncogenic mutations.

Changed Pazopanib in Gastrointestinal Stromal Tumour with KIT : 3

Alterations changed: Oncogenic mutations.

Changed Savolitinib in Papillary Renal Cell Carcinoma with MET : 3

Alterations changed: Oncogenic mutations, AmplificationOncogenic mutation, Amplification.

Changed GSK2256098 in Meningioma with NF2 : 3

Alterations changed: Oncogenic mutations.

Changed Capivasertib + Paclitaxel in Triple-negative breast cancer with PTEN : 3

Alterations changed: Loss-of-function mutations.

Changed Ipatasertib + Paclitaxel in Breast Cancer with AKT1 : 4

Alterations changed: Oncogenic mutations.

Changed PF-03084014, Gamma secretase inhibitor in Aggressive Fibromatosis with APC : 4

Alterations changed: Loss-of-function mutations.

Changed Olaparib in Neuroblastoma with ATRX : 4

Alterations changed: Loss-of-function mutations.

Changed Adavosertib in Solid tumours with ATRX : 4

Alterations changed: Loss-of-function mutations.

Changed CX-5461, CX-5461 + Olaparib in Ovarian cancer with BRCA1 : 4

Alterations changed: Oncogenic mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with BRCA2 : 4

Alterations changed: Oncogenic mutations.

Changed CX-5461, CX-5461 + Olaparib in Ovarian cancer with BRCA2 : 4

Alterations changed: Oncogenic mutations.

Changed Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Melanoma with BRD7 : 4

Alterations changed: Loss-of-function mutations.

Changed Olaparib in Prostate cancer with BRIP1 : 4

Alterations changed: Oncogenic mutations.

Changed Crizotinib, Foretinib in Breast Cancer with CDH1 : 4

Alterations changed: Loss-of-function mutations.

Changed Pembrolizumab, Atezolizumab, Nivolumab + Ipilimumab, Durvalumab + Tremelimumab in Prostate cancer with CDK12 : 4

Alterations changed: Loss-of-function mutations.

Changed Palbociclib in Pancreatic Adenocarcinoma with CDKN2A : 4

Alterations changed: Loss-of-function mutations.

Changed VE-821 in Solid tumours with CHEK1 : 4

Alterations changed: Loss-of-function mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with CHEK1 : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with CHEK1 : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with CHEK2 : 4

Alterations changed: Oncogenic mutations.

Changed Afatinib in Non-Small Cell Lung Cancer with EGFR : 4

Alterations changed: Amplification AND NOT Oncogenic mutations.

Changed Patritumab Deruxtecan in Non-Small Cell Lung Cancer with EGFR : 4

Alterations changed: Oncogenic mutations.

Changed Osimertinib + Crizotinib, Osimertinib + Alectinib in Non-Small Cell Lung Cancer with EGFR+ALK : 4

Alterations changed: EGFR:Oncogenic mutations and ALK:fusionEGFR:oncogenic mutation and ALK:fusion.

Changed Dabrafenib + Trametinib + Osimertinib in Non-Small Cell Lung Cancer with EGFR+BRAF : 4

Alterations changed: EGFR:Oncogenic mutations and BRAF:V600EEGFR:oncogenic mutation and BRAF:V600E.

Changed Osimertinib + Ado-Trastuzumab Emtansine in Non-Small Cell Lung Cancer with EGFR+ERBB2 : 4

Alterations changed: EGFR:Oncogenic mutations and ERBB2:amplificationEGFR:oncogenic mutation and ERBB2:amplification.

Changed Gefitinib + Savolitinib in Non-Small Cell Lung Cancer with EGFR+MET : 4

Alterations changed: EGFR:Oncogenic mutations and MET:amplification and NOT EGFR:T790MEGFR:oncogenic mutation and MET:amplification and NOT EGFR:T790M.

Changed Osimertinib + Pralsetinib in Non-Small Cell Lung Cancer with EGFR+RET : 4

Alterations changed: EGFR:Oncogenic mutations and RET:fusionEGFR:oncogenic mutation and RET:fusion.

Changed Osimertinib + Crizotinib in Non-Small Cell Lung Cancer with EGFR+ROS1 : 4

Alterations changed: EGFR:Oncogenic mutations and ROS1:fusionEGFR:oncogenic mutation and ROS1:fusion.

Changed Afatinib in Lung adenocarcinoma with ERBB2 : 4

Alterations changed: Oncogenic mutations.

Changed Erlotinib in Cholangiocarcinoma with ERRFI1 : 4

Alterations changed: E384X, Loss-of-function mutations, deletionE384X, Loss-of-function mutation, deletion.

Changed Tazemetostat in Non-Hodgkin’s Lymphoma with EZH2 : 4

Alterations changed: Oncogenic mutations, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687VOncogenic mutation, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687V.

Changed Tazemetostat in Solid tumours with EZH2 : 4

Alterations changed: Oncogenic mutations, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687VOncogenic mutation, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687V.

Changed Talazoparib in Lung Squamous Cell Carcinoma with FANCC : 4

Alterations changed: Oncogenic mutations.

Changed Veliparib in Non-Small Cell Lung Cancer with FANCD2 : 4

Alterations changed: Loss-of-function mutations, Oncogenic mutationsLoss-of-function mutation, Oncogenic mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with FANCM : 4

Alterations changed: Oncogenic mutations.

Changed ATR inhibitor in Solid tumours with FANCM : 4

Alterations changed: S1045, Loss-of-function mutations.

Changed AZD4547 in Solid tumours with FGFR1 : 4

Alterations changed: Amplification, Fusion, Oncogenic mutations.

Changed Erdafitinib in Solid tumours with FGFR1 : 4

Alterations changed: Amplification, Fusion, Oncogenic mutations and NOT V561Amplification, Fusion, Oncogenic mutation and NOT V561.

Changed Erdafitinib in Lung Squamous Cell Carcinoma with FGFR1 : 4

Alterations changed: Amplification, Oncogenic mutations.

Changed Erdafitinib in Solid tumours with FGFR2 : 4

Alterations changed: Amplification, Fusion, Oncogenic mutations and NOT V564Amplification, Fusion, Oncogenic mutation and NOT V564.

Changed Erdafitinib in Lung Squamous Cell Carcinoma with FGFR3 : 4

Alterations changed: Amplification, Fusion, Oncogenic mutations.

Changed Erdafitinib in Solid tumours with FGFR3 : 4

Alterations changed: Amplification, Fusion, Oncogenic mutations and NOT V565 and NOT V550Amplification, Fusion, Oncogenic mutation and NOT V565 and NOT V550.

Changed SHP2 inhibitor in Non-Small Cell Lung Cancer with KRAS : 4

Alterations changed: Oncogenic mutations.

Changed Trametinib in Non-Small Cell Lung Cancer with KRAS : 4

Alterations changed: Oncogenic mutations.

Changed Trametinib + Ponatinib in Non-Small Cell Lung Cancer with KRAS : 4

Alterations changed: Oncogenic mutations.

Changed Binimetinib in Ovarian cancer with KRAS : 4

Alterations changed: Oncogenic mutations.

Changed GGTI-2418 in Solid tumours with KRAS : 4

Alterations changed: Oncogenic mutations.

Changed Trametinib in Chronic myelogenous leukaemia with LZTR1 : 4

Alterations changed: Loss-of-function mutations.

Changed Olaparib in Prostate cancer with NBN : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with NBN : 4

Alterations changed: Oncogenic mutations.

Changed SHP099 in Malignant peripheral nerve sheath tumor with NF1 : 4

Alterations changed: Loss-of-function mutations, deletionLoss-of-function mutation, deletion.

Changed Trametinib + RMC-4550, SHP099 in Malignant peripheral nerve sheath tumor with NF1 : 4

Alterations changed: Loss-of-function mutations, deletionLoss-of-function mutation, deletion.

Changed RMC-4630 + Cobimetinib in Solid tumours with NF1 : 4

Alterations changed: Oncogenic mutations.

Changed Mirdametinib + JQ1 in Malignant peripheral nerve sheath tumor with NF1+SUZ12 : 4

Alterations changed: NF1:Loss-of-function mutations AND SUZ12:Loss-of-function mutationsNF1:loss-of-function mutation AND SUZ12:loss-of-function mutation.

Changed Everolimus + Docetaxel in Urothelial Carcinoma with NF2 : 4

Alterations changed: Loss-of-function mutations.

Changed VT3989 in Mesothelioma, Solid tumours with NF2 : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with PALB2 : 4

Alterations changed: Oncogenic mutations.

Changed Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Melanoma with PBRM1 : 4

Alterations changed: Loss-of-function mutations.

Changed Talazoparib, Olaparib, Rucaparib, Berzosertib, Ceralasertib in Renal Cell Carcinoma, Solid tumours with PBRM1 : 4

Alterations changed: Loss-of-function mutations; Oncogenic mutationsLoss-of-function mutation; Oncogenic mutation.

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with PRKDC : 4

Alterations changed: Oncogenic mutations, Loss-of-function mutations.

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with PRKDC : 4

Alterations changed: Oncogenic mutations, Loss-of-function mutations.

Changed Ipatasertib in Solid tumours with PTEN : 4

Alterations changed: Loss-of-function mutations.

Changed Ipatasertib + Paclitaxel in Breast Cancer with PTEN : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with RAD51B : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with RAD51D : 4

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with RAD54L : 4

Alterations changed: Oncogenic mutations.

Changed Trametinib in Non-Small Cell Lung Cancer with RASA1 : 4

Alterations changed: Loss-of-function mutations; Oncogenic mutationsLoss-of-function mutation; Oncogenic mutation.

Changed LY3295668 in Solid tumours with RB1 : 4

Alterations changed: Oncogenic mutations, Loss-of-function mutations, loss of protein expressionOncogenic mutations, Loss-of-function mutation, loss of protein expression.

Changed Olaparib in Solid tumours with SLX4 : 4

Alterations changed: Loss-of-function mutations.

Changed Tazemetostat in Ovarian Small Cell Carcinoma with SMARCA2 : 4

Alterations changed: Loss-of-function mutations.

Changed Palbociclib in Non-Small Cell Lung Cancer with SMARCA4 : 4

Alterations changed: Loss-of-function mutations.

Changed Palbociclib in Ovarian Small Cell Carcinoma with SMARCA4 : 4

Alterations changed: Loss-of-function mutations.

Changed Tazemetostat in Ovarian Small Cell Carcinoma with SMARCA4 : 4

Alterations changed: Loss-of-function mutations.

Changed Tazemetostat in Ovarian Small Cell Carcinoma with SMARCA4 : 4

Alterations changed: Loss-of-function mutations.

Changed Tazemetostat in Rhabdoid tumors with SMARCB1 : 4

Alterations changed: Oncogenic mutations.

Changed JQ1 in Solid tumours with SUZ12 : 4

Alterations changed: Loss-of-function mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with ATM : R2

Alterations changed: Oncogenic mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with ATR : R2

Alterations changed: Oncogenic mutations.

Changed Nilotinib, Dasatinib, Ponatinib in Chronic myelogenous leukaemia with BAP1 : R2

Alterations changed: Loss-of-function mutations.

Changed Olaparib, Talazoparib in Mesothelioma with BAP1 : R2

Alterations changed: Loss-of-function mutations.

Changed Osimertinib in Non-Small Cell Lung Cancer with BRAF : R2

Alterations changed: Oncogenic mutations, fusionOncogenic mutation, fusion.

Changed Dabrafenib + Trametinib in Non-Small Cell Lung Cancer with BRAF+PTEN : R2

Alterations changed: BRAF:V600E AND PTEN:Oncogenic mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with BRCA1 : R2

Alterations changed: Oncogenic mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with BRCA2 : R2

Alterations changed: Oncogenic mutations.

Changed Palbociclib in Pancreatic Adenocarcinoma, Cholangiocarcinoma, Gallbladder Cancer with CDKN2A : R2

Alterations changed: Loss-of-function mutations, Oncogenic mutationsLoss-of-function mutation, oncogenic mutations.

Changed Palbociclib in Triple-negative breast cancer with CDKN2A : R2

Alterations changed: Oncogenic mutations.

Changed Pembrolizumab, Atezolizumab, Nivolumab, Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-Small Cell Lung Cancer with EGFR : R2

Alterations changed: Oncogenic mutations.

Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+ALK : R2

Alterations changed: EGFR:Oncogenic mutations and ALK:fusionEGFR:oncogenic mutation and ALK:fusion.

Changed Osimertinib in Non-Small Cell Lung Cancer with EGFR+BRAF : R2

Alterations changed: EGFR:Oncogenic mutations and BRAF:V600EEGFR:oncogenic mutation and BRAF:V600E.

Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+RB1 : R2

Alterations changed: EGFR:Oncogenic mutations and RB1:Oncogenic mutationsEGFR:oncogenic mutation and RB1:oncogenic mutation.

Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+RET : R2

Alterations changed: EGFR:Oncogenic mutations and RET:fusionEGFR:oncogenic mutation and RET:fusion.

Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+ROS1 : R2

Alterations changed: EGFR:Oncogenic mutations and ROS1:fusionEGFR:oncogenic mutation and ROS1:fusion.

Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+TP53 : R2

Alterations changed: EGFR:Oncogenic mutations and TP53:Oncogenic mutationsEGFR:oncogenic mutation and TP53:oncogenic mutation.

Changed Neratinib in Solid tumours with ERBB3 : R2

Alterations changed: Oncogenic mutations, R103G, V104L, V104M, G284R, D297Y, T355A, E928GOncogenic mutation, R103G, V104L, V104M, G284R, D297Y, T355A, E928G.

Changed Cetuximab in Head and Neck Squamous Cell Carcinoma with ERBB4 : R2

Alterations changed: Oncogenic mutations.

Changed Pembrolizumab in Melanoma with FBXW7 : R2

Alterations changed: Loss-of-function mutations, R505Loss-of-function mutation, R505.

Changed Pembrolizumab in Colorectal Cancer with KRAS+Microsatellite Instability : R2

Alterations changed: KRAS:Oncogenic mutations AND Microsatellite Instability:HighKRAS:oncogenic mutation AND Microsatellite Instability:High.

Changed Pembrolizumab in Colorectal Cancer with KRAS+Mismatch repair : R2

Alterations changed: KRAS:Oncogenic mutations AND Mismatch repair:deficientKRAS:oncogenic mutation AND Mismatch repair:deficient.

Changed Imatinib, Ponatinib in Chronic myelogenous leukaemia with LZTR1 : R2

Alterations changed: Loss-of-function mutations.

Changed Crizotinib in Non-Small Cell Lung Cancer with MET+TP53 : R2

Alterations changed: MET:Exon 14 skipping mutation and TP53:Oncogenic mutations.

Changed Imatinib, Nilotinib, Dasatinib, Bosutinib, Ponatinib in Chronic myelogenous leukaemia with NF1 : R2

Alterations changed: Loss-of-function mutations.

Changed Crizotinib in Non-Small Cell Lung Cancer with NF1 : R2

Alterations changed: Oncogenic mutations.

Changed Talazoparib in Lung Squamous Cell Carcinoma with PALB2 : R2

Alterations changed: Oncogenic mutations.

Changed MK2206 in Colorectal Cancer with PIK3CA : R2

Alterations changed: Oncogenic mutations.

Changed Taselisib in Lung Squamous Cell Carcinoma with PIK3CA : R2

Alterations changed: Oncogenic mutations.

Changed Osimertinib in Non-Small Cell Lung Cancer with PIK3CA : R2

Alterations changed: Oncogenic mutations.

Changed Olaparib in Prostate cancer with PPP2R2A : R2

Alterations changed: Oncogenic mutations.

Changed GSK2636771 in Solid tumours with PTEN : R2

Alterations changed: Loss-of-function mutations, loss of protein expressionLoss-of-function mutation, loss of protein expression.

Changed Imatinib, Nilotinib, Dasatinib, Ponatinib in Chronic myelogenous leukaemia with PTPN11 : R2

Alterations changed: Loss-of-function mutations.

Changed Vismodegib in Basal Cell Carcinoma with SUFU : R2

Alterations changed: Loss-of-function mutations.

Changed Imatinib, Nilotinib, Dasatinib, Bosutinib, Ponatinib in Chronic myelogenous leukaemia with WT1 : R2

Alterations changed: Loss-of-function mutations.

Wednesday, 2 June 2021 (Version: 20210602AU)

Changed Adavosertib in Uterine Serous Carcinoma with TP53 Oncogenic mutations: 3

Comments changed: Single arm phase II trial with adavosertib in USC with TP53 alterations (predefined hypothesis). ORR 29% with PFS at 6 months 47%. Note: TP53 mutation was prespecified in the hypothesis of study, although TP53 alone is likely insufficient for predicting sensitivity to WEE1 inhibition..

Changed Therapy in Solid tumours except Colorectal Cancer with Tumour Mutational Burden High: 3

Therapy changed: Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibodyAnti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody.

Changed Therapy in Solid tumours with LRP1B Oncogenic mutations, deletions, truncating mutations, loss-of-function mutations: 4

Therapy changed: Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibodyAnti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody.

Changed Therapy in Solid tumours with Tumour Mutational Burden High: 4

Therapy changed: Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, immune checkpoint blockade,PD-1 targeting, immune checkpoint blockade,PD-L1 targetingAnti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, immune checkpoint blockade,PD-1 targeting, immune checkpoint blockade,PD-L1 targeting.

Changed Therapy in Non-Small Cell Lung Cancer with ALK Fusion: R2

Therapy changed: Pembrolizumab, Atezolizumab, Nivolumab, Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibodyPembrolizumab, Atezolizumab, Nivolumab, Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody.

Changed Therapy in Non-Small Cell Lung Cancer with EGFR Oncogenic mutation: R2

Therapy changed: Pembrolizumab, Atezolizumab, Nivolumab, Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibodyPembrolizumab, Atezolizumab, Nivolumab, Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody.

Changed Everolimus in Solid tumours with PIK3CA

Alterations changed: Amplification, Oncogenic mutations. Tier changed: R24. Comments changed: Phase II Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.Negative Phase 2 but small sample size..

Changed Everolimus in Solid tumours with PTEN

Alterations changed: Loss of protein expression, Loss-of-function mutations. Tier changed: R24. Comments changed: Phase II Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.Negative Phase 2 but small sample size..

Tuesday, 1 June 2021 (Version: 20210601AU)

New Osimertinib in Non-Small Cell Lung Cancer with EGFR G719, L747S, S768I, L861Q: 3

Phase II KCSG-LU15-09: Osimertinib for Patients With NSCLC harboring uncommon EGFR Mutations. N=37, ORR 50%. References: 31825714

New Osimertinib in Non-Small Cell Lung Cancer with EGFR G719, S768I, L861Q: 4

Patient-derived xenografts (PDX) and cell lines studies. References: 32943544

Removed RAF dimer inhibitor in Solid tumours with BRAF alterations L597, L597Q: Tier 4

Changed BCL6 inhibitor with BCL6 Protein expression: 4

Cancer type(s) changed: Breast cancer, Diffuse Large B-Cell lymphomaBreast cancer, Diffuse Large B Cell lymphoma

Changed RAF dimer inhibitor in Solid tumours with BRAF : 4

Alterations changed: L597, L597Q, K601, K601E.

Changed Osimertinib in Glioblastoma with EGFR vIII: 4

Comments changed: Osimertinib inhibited an EGFR vIII glioblastoma cell line and associated xenograft models.Osimertinib inhibited cell line and xenograft models of an EGFR vIII cell line..

Monday, 31 May 2021 (Version: 20210531AU)

New Osimertinib in Glioblastoma with EGFR A289V: 4

Case report of complete response of left frontal lobe tumor after 4 weeks of osimertinib. References: 31769726

New Osimertinib in Glioblastoma with EGFR vIII: 4

Osimertinib inhibited cell line and xenograft models of an EGFR vIII cell line. References: 32547705

Changed Brentuximab Vedotin with CD30 Protein expression: 1

Cancer type(s) changed: Hodgkin’s LymphomaHodgkins Lymphoma

Changed Selumetinib with NF1 Oncogenic mutations (germline): 2

Cancer type(s) changed: Glioma, Paediatric low grade gliomas, Type 1 neurofibromatosisGliomas, Paediatric low grade gliomas, Type 1 neurofibromatosis

Changed Pembrolizumab with Tumour Mutational Burden High: 2

Cancer type(s) changed: Cervical cancer, Endometrial cancer, Neuroendocrine tumour, Salivary gland cancers, Small-cell lung cancer, Thyroid cancer, Vulvar cancerCervical cancer, Endometrial cancer, Neuroendocrine tumour, Salivary gland carcinoma, Small-cell lung cancer, Thyroid cancer, Vulvar cancer

Changed Capmatinib + Gefitinib in Non-Small Cell Lung CancerMET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R: 3

Biomarker changed: EGFR+METMET+EGFR.

Changed Tepotinib + Gefitinib in Non-Small Cell Lung CancerMET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R: 3

Biomarker changed: EGFR+METMET+EGFR.

Changed Ibrutinib with TP53 Alteration: 3

Cancer type(s) changed: Chronic lymphocytic leukaemiaChronic Lymphocytic Leukemia

Changed CYP17A1 inhibitor with AR Protein expression: 4

Cancer type(s) changed: Gliomas

Changed Nivolumab, Atezolizumab in Urothelial Carcinoma with ARID1A : 4

Alterations changed: Oncogenic mutations.

Changed Anti-PD-1 monoclonal antibody in Melanoma with ARID2 : 4

Alterations changed: Loss-of-function mutations.

Changed Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Melanoma with ARID2 : 4

Alterations changed: Loss-of-function mutations.

Changed BAY-1895344 in Solid tumours with ATM : 4

Alterations changed: Loss of protein expression; Loss-of-function mutations.

Changed Olaparib in Prostate cancer with BARD1 : 4

Alterations changed: Oncogenic mutations.

Changed Venetoclax with BCL2 Amplification: 4

Cancer type(s) changed: Small-Cell Lung CancerSmall Cell Lung Cancer

Changed Amivantamab in Non-Small Cell Lung CancerMET:Alteration and EGFR:Oncogenic mutations: 4

Biomarker changed: EGFR+METMET+EGFR.

Changed Tazemetostat with EZH2 Oncogenic mutation, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687V: 4

Cancer type(s) changed: Non-Hodgkin’s LymphomaNon-Hodgkin Lymphoma

Changed Trametinib with LZTR1 Loss-of-function mutation: 4

Cancer type(s) changed: Chronic myelogenous leukaemiaChronic myeloid leukaemia

Changed Ipatasertib + Paclitaxel in Breast Cancer with PIK3CA : 4

Alterations changed: Oncogenic mutations.

Changed Therapy in Non-Small Cell Lung Cancer with ALK L1196M and L1198F, L1198F and C1156Y, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A: R2

Therapy changed: Alectinib, Brigatinib, Ceritinib, LorlatinibAlectinib, Brigatinib, Ceritinib, Lorlatinib.

Changed Nilotinib, Dasatinib, Ponatinib with BAP1 Loss-of-function mutation: R2

Cancer type(s) changed: Chronic myelogenous leukaemiaChronic myeloid leukaemia

Changed Imatinib, Ponatinib with LZTR1 Loss-of-function mutation: R2

Cancer type(s) changed: Chronic myelogenous leukaemiaChronic myeloid leukaemia

Changed Imatinib, Nilotinib, Dasatinib, Bosutinib, Ponatinib with NF1 Loss-of-function mutation: R2

Cancer type(s) changed: Chronic myelogenous leukaemiaChronic myeloid leukaemia

Changed Imatinib, Nilotinib, Dasatinib, Ponatinib with PTPN11 Loss-of-function mutation: R2

Cancer type(s) changed: Chronic myelogenous leukaemiaChronic myeloid leukaemia

Changed Imatinib, Nilotinib, Dasatinib, Bosutinib, Ponatinib with WT1 Loss-of-function mutation: R2

Cancer type(s) changed: Chronic myelogenous leukaemiaChronic myeloid leukaemia

Sunday, 30 May 2021 (Version: 20210530AU)

Changed Lenvatinib in Pancreatic neuroendocrine tumour, neuroendocrine tumour with SSTR2 Protein expression: 3

References changed: 33945297.

Saturday, 29 May 2021 (Version: 20210529AU)

New Lenvatinib in Pancreatic neuroendocrine tumour, neuroendocrine tumour with SSTR2 Protein expression: 3

Phase 2 TALENT trial. In patients with pancreatic and gastrointestinal NET previously treated with somatostatin analogues and/or targeted agents, Lenvatinib resulted in 30% with DOR of 21.5 months. Somatostatin receptor positivity is implied. References:

New Dabrafenib + Trametinib + Osimertinib in Non-Small Cell Lung Cancer with EGFR+BRAF EGFR:oncogenic mutation and BRAF:V600E: 4

Case report. References: 33580193

New Osimertinib in Non-Small Cell Lung Cancer with EGFR+BRAF EGFR:oncogenic mutation and BRAF:V600E: R2

Case report. References: 33580193

Changed Infigratinib in Cholangiocarcinoma with FGFR2 Fusions

Tier changed: 23. Comments changed: Not TGA approved. FDA accelerated approved for use in second-line and beyond. Phase II study (NCT02150967) with N=108. ORR: 23%. Median PFS 7.3 months.Activities seen, but not superior to chemotherapy in a retrospective review. References changed: 10.1200/JCO.2021.39.3_suppl.265, 10.1200/JCO.2020.38.15_suppl.4591.

Changed Sotorasib in Non-Small Cell Lung Cancer with KRAS G12C

Tier changed: 23. Comments changed: Not TGA approved. FDA approved for second-line and beyond. CODEBREAK 100 ORR 32.2%.

Friday, 28 May 2021 (Version: 20210528AU)

Changed MEK inhibitor + anti-EGFR monoclonal antibody in Solid tumours with BRAF : 4

Alterations changed: Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596RClass III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R.

Changed RMC-4630 + Cobimetinib in Solid tumours with BRAF : 4

Alterations changed: Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596RClass III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R.

Changed PLX8394 in Solid tumours with BRAF : R2

Alterations changed: Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596RClass III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R.

Changed Vemurafenib, Dabrafenib in Solid tumours with BRAF : R2

Alterations changed: Class III mutations, D287H, V459L, G466V, G466E, G466A, S467L, N581S, N581I, D594N, D594G, D594A, D594H, F595L, G596D, G596RClass III mutations, D287H, V459L, G466V, G466E, G466A, S467L, G469E, N581S, N581I, D594N, D594G, D594A, D594H, F595L, G596D, G596R.

Thursday, 27 May 2021 (Version: 20210527AU)

Changed Erlotinib in Non-Small Cell Lung Cancer with EGFR : 4

Alterations changed: Amplification AND L858R; Amplification AND Exon 19 deletion. Comments changed: Retrospective study showing the subgroup with EGFR amplification and sensitizing mutations had prolonged PFS and ORR than those without..

Changed Afatinib in Non-Small Cell Lung Cancer with EGFR : 4

Alterations changed: Amplification AND NOT Oncogenic mutation. Comments changed: . ORR of 4/43 (9%) in the EGFR FISH-positive subgroup (gene/chr ratio >= 2, or Copy number >= 15) without EGFR sensitising mutation.Poor ORR 4/43 (9%) without mutation.

Changed Afatinib in Solid tumours with EGFR Amplification

Tier changed: R24. Comments changed: Phase 2 study. Five patients in the EGFR amplified, FISH-Positive subgroup had ORR 0%.Poor ORR (5%). Negative phase 2 study.

Changed Gefitinib in Solid tumours with EGFR Amplification

Tier changed: R24. Comments changed: Phase 2 study (N=15) with 1 PR in EGFR-amplified glioblastoma multiforme. ORR 7%.Poor ORR (7%). Negative phase 2 study.

Wednesday, 26 May 2021 (Version: 20210526AU)

Changed Neratinib in Solid tumours with ERBB3 : R2

Alterations changed: Oncogenic mutation, R103G, V104L, V104M, G284R, D297Y, T355A, E928G. Comments changed: SUMMIT. No response seen in patients with ERBB3 hotspot mutations..

Tuesday, 25 May 2021 (Version: 20210525AU)

New Talazoparib, Olaparib, Rucaparib, Berzosertib, Ceralasertib in Renal Cell Carcinoma, Solid tumours with PBRM1 Loss-of-function mutation; Oncogenic mutation: 4

PARP and ATR inhibitors were shown to be synthetically lethal in PBRM1-deficient tumours in cell line and Xenograft models. References: 33888468

Monday, 24 May 2021 (Version: 20210524AU)

New Anti-PD-1 monoclonal antibody in Melanoma with ARID2 Loss-of-function mutation: 4

ARID2 deficiency leads increased CD274 expression, increased expression of T-cell-attracting chemokines, and effectiveness of anti-PD-L1 therapy in murine melanoma model. References: 33333124

New Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Melanoma with ARID2 Loss-of-function mutation: 4

Inactivation of genes encoding components of the PBAF complex complex sensitised mouse B16F10 melanoma cells to killing by T cells. References: 29301958

New BAY-1895344 in Solid tumours with ATM Loss of protein expression; Loss-of-function mutation: 4

Phase 1 study of BAY-1895344. 4 of 11 patients with ATM protein loss or loss of function mutations had objective response in appendiceal, endometrial, breast, and urothelial carcinomas. SD was seen in 8 patients. References: 32988960

New Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Melanoma with BRD7 Loss-of-function mutation: 4

Inactivation of genes encoding components of the PBAF complex complex sensitised mouse B16F10 melanoma cells to killing by T cells. References: 29301958

New Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody in Melanoma with PBRM1 Loss-of-function mutation: 4

Inactivation of genes encoding components of the PBAF complex complex sensitised mouse B16F10 melanoma cells to killing by T cells. References: 29301958

Saturday, 22 May 2021 (Version: 20210522AU)

Changed Amivantamab in Non-Small Cell Lung Cancer with EGFR C797S, Exon 20 insertion

Tier changed: 24.

Changed Amivantamab in Non-Small Cell Lung Cancer with EGFR Exon 20 insertion

Tier changed: 24. Comments changed: Not TGA approved. FDA accelerated approval 21/05/2021. CHRYSALIS. ORR 36%.

Changed Selumetinib with NF1 Oncogenic mutations (germline): 2

Cancer type(s) changed: Gliomas, Paediatric low grade gliomas, Type 1 neurofibromatosisGliomas, Paediatric low grade gliomas, Type 1 neurofibromatosis

Wednesday, 19 May 2021 (Version: 20210519AU)

New Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab in Ovarian cancer with CD274 Protein expression: 4

IMagyn050/GOG3015/ENGOT-OV39: Phase III trial of Chemotherapy and Bevacizumab with or without Atezolizumab. In intention-to-treat population, the median PFS was 19.5 vs 18.4 months (for IO+Chemo+Bevacizumab vs Chemo+Bevacizumab) respectively. Exploratory analysis as shown in PFS in subgroup analysis suggests that improvement in small population with IC >= 5% (HR 0.64) and TC >= 1% (HR 0.41). References: 33891472

Wednesday, 12 May 2021 (Version: 20210512AU)

New Rucaparib in Pancreatic Adenocarcinoma with BRCA1 Oncogenic mutations (germline): 3

Phase 2 trial of maintenance Rucaparib (after first-line chemotherapy) in platinum-sensitive advanced pancreatic cancer. PFS6 60% with median 13.1 months. ORR 42% in 36 patients. References: 33970687

New Rucaparib in Pancreatic Adenocarcinoma with BRCA2 Oncogenic mutations (germline), Oncogenic mutations: 3

Phase 2 trial of maintenance Rucaparib (after first-line chemotherapy) in platinum-sensitive advanced pancreatic cancer. PFS6 60% with median 13.1 months. ORR 42% in 36 patients. References: 33970687

New Rucaparib in Pancreatic Adenocarcinoma with PALB2 Oncogenic mutations (germline): 3

Phase 2 trial of maintenance Rucaparib (after first-line chemotherapy) in platinum-sensitive advanced pancreatic cancer. PFS6 60% with median 13.1 months. ORR 42% in 36 patients. References: 33970687

Tuesday, 11 May 2021 (Version: 20210511AU)

New Carboxyamidotriazole Orotate + Temozolomide in Glioblastoma with EGFR Amplification: 4

Exploratory analysis from the phase 1 study showed high rate of responses in EGFR-amplified tumors. References: 29683790

New Dacomitinib in Glioblastoma with EGFR Amplification + G598V: 4

Phase II: Dacomitinib was not effecitive in EGFR-amplified GBM (5/30 patients in arm B achieved PFS6 and did not meet the primary endpoint). References: 10.1200/PO.19.00295

New Afatinib + Temozolomide in Glioblastoma with EGFR vIII + D247Y: 4

Case report: prolonged response to afatinib with temozolomide in recurrent multifocal GBM. References: 26423602

New Lapatinib in Glioblastoma with EGFR vIII, T263P, A289D, A289V, G598V: 4

Cells with EGFR ectodomain mutation have increased sensitivity to lapatinib, but lapatinib did not achieve sufficient intratumoral concentrations in GBM patients. Response to lapatinib was not assessable. References: 22588883

New Dacomitinib in Glioblastoma with EGFR Amplification: R2

Phase II: Dacomitinib was not effecitive in EGFR-amplified GBM. A subset experienced a durable, clinically meaningful benefit (2/4 G598V with TTP>=6 months). References: 10.1200/PO.19.00295

New Depatuxizumab mafodotin in Glioblastoma with EGFR Amplification: R2

INTELLANCE 2/EORTC 1410: Randomized Phase 2 trial. No evidence of efficacy in the monotherapy arm was observed (vs. control arm Temozolomide or Lomustine). References: 31747009

Thursday, 6 May 2021 (Version: 20210506AU)

New TetMYB in Solid tumours, Adenoid cystic carcinoma, Colorectal cancer with MYB Alteration; Overexpression: 4

References: 31650066

Tuesday, 4 May 2021 (Version: 20210504AU)

Changed Sacituzumab Govitecan in Triple-negative breast cancer with ESR1+ERBB2 NOT ESR1:protein expression and NOT ERBB2:amplified: 2

Comments changed: Not TGA approved; FDA approved. Anti Trop-2 ADC. Phase 1/2: ORR 33%. Median DOR 7.7 months. CBR 45%. Median PFS: 5.5 months. Phase 3 ASCENT trial: OS: 12.1 vs 6.7 months (chemotherapy).. References changed: 30786188, 33882206.

Friday, 30 April 2021 (Version: 20210430AU)

Changed Pembrolizumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with CD274 Protein expression

Tier changed: 32. Comments changed: Not TGA approved. KEYNOTE-059: Phase 2 single arm study in previously treated disease (third-line and beyond). ORR 16% in PD-L1 positivity (defined as CPS >= 1%, 22C3 pharmDx assay). DOR: 16.3 months. FDA accelerated approval in 2017, but reviewed 2021 due to low response rate and negative confirmatory trial KEYNOTE-061.Not TGA approved. FDA approved. KEYNOTE-059: Phase 2 single arm study in previously treated disease. ORR 16% in PD-L1 positivity (defined as CPS >= 1%, 22C3 pharmDx assay). DOR: 16.3 months..

Wednesday, 28 April 2021 (Version: 20210428AU)

New Cetuximab, Cetuximab + Irinotecan in Colorectal Cancer with KRAS G13D: R2

ORR 0% in G13D mutant mCRC. References: 27114605

New Dabrafenib + Trametinib in Melanoma with MAPK1 Y131F, A189V, S202P, D321G, E322K: R2

Cell line mutagenesis screen following RAF/MEKi exposure. References: 25320010

New VX11E in Melanoma with MAPK1 Y36N, Y36H, P58S, P58L, P58T, Y64N, C65Y: R2

Cell line mutagenesis screen following ERKi exposure. References: 25320010

New Dabrafenib + Trametinib in Melanoma with MAPK3 C82Y, R84H, Q90R, Y148H, A206V, S219P: R2

Cell line mutagenesis screen following RAF/MEKi exposure. References: 25320010

New VX11E in Melanoma with MAPK3 Y53H, G54A, S74G, P75L, Y81C, C82Y, G186D: R2

Cell line mutagenesis screen following ERKi exposure. References: 25320010

New Trametinib in Non-Small Cell Lung Cancer with RASA1 Loss-of-function mutation; Oncogenic mutation: 4

References: 29127119

Removed Olaparib + Durvalumab in Breast Cancer with BRCA1 alterations Oncogenic mutations (germline): Tier 3

Removed Durvalumab + Olaparib in Breast Cancer with BRCA2 alterations Oncogenic mutations (germline): Tier 3

Changed Durvalumab + Olaparib in Breast Cancer with BRCA1 Oncogenic mutations (germline): 3

Comments changed: MEDIOLA breast cancer cohort, including both TNBC and non-TNBC. Maximum of two lines of prior treatments. ORR 63%. DCR 28 weeks: 50%. Note: PD-L1 (at 1%) status NS.MEDIOLA. ORR 63%.

Changed Therapy in Non-Small Cell Lung Cancer with ALK L1196M and L1198F, L1198F and C1156Y, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A: R2

Therapy changed: Alectinib, Brigatinib, Ceritinib, LorlatinibAlectinib, Brigatinib, Ceritinib, Lolartinib.

Saturday, 24 April 2021 (Version: 20210424AU)

New TPX-0131 in Non-Small Cell Lung Cancer with ALK Fusion, T1151M, T1151_L1152insT, L1152R, L1152P, C1156Y, I1171N, F1174L, F1174S, F1174C, V1180L, L1196M and L1198F, L1198F and C1156Y, L1198F, G1202R and L1198F, G1202R, G1202del, D1203N, D1203N and E1210K, S1206R, E1210K and S1206C, E1210K, L1196M, F1245C, G1269A, S1269S, R1275Q: 4

Cell line assays comparing TPX-0131 against Approved ALK inhibitors. References: 10.1158/1538-7445.AM2020-5226

New Crizotinib in Non-Small Cell Lung Cancer with ALK G1269S: R2

Cell line assays comparing TPX-0131 against Approved ALK inhibitors. References: 10.1158/1538-7445.AM2020-5226

New Alectinib in Non-Small Cell Lung Cancer with ALK I1171N, G1202R, G1202del: R2

Cell line assays comparing TPX-0131 against Approved ALK inhibitors. References: 10.1158/1538-7445.AM2020-5226

New Crizotinib in Non-Small Cell Lung Cancer with ALK L1196M and L1198F, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A: R2

Cell line assays comparing TPX-0131 against Approved ALK inhibitors. References: 10.1158/1538-7445.AM2020-5226

New Alectinib, Brigatinib, Ceritinib, Lolartinib in Non-Small Cell Lung Cancer with ALK L1196M and L1198F, L1198F and C1156Y, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A: R2

Cell line assays comparing TPX-0131 against Approved ALK inhibitors. References: 10.1158/1538-7445.AM2020-5226

New Ceritinib in Non-Small Cell Lung Cancer with ALK L1198F, G1202R: R2

Cell line assays comparing TPX-0131 against Approved ALK inhibitors. References: 10.1158/1538-7445.AM2020-5226

Friday, 23 April 2021 (Version: 20210423AU)

New Dostarlimab in Endometrial Carcinoma with Microsatellite Instability High: 2

GARNET trial: dMMR as assessed by IHC or MSI-H by PCR or NGS. ORR 43% with 13% CR. Duration of response at 6 months: 96%. FDA approved. References: 33001143

New Dostarlimab in Endometrial Carcinoma with Mismatch repair Deficient: 2

GARNET trial: dMMR as assessed by IHC or MSI-H by PCR or NGS. ORR 43% with 13% CR. Duration of response at 6 months: 96%. FDA approved. References: 33001143

New Dostarlimab in Solid tumours with Mismatch repair Deficient: 3

GARNET: ORR 39% in dMMR patients across tumour types. Note no response seen in 4 pancreatic cancer cases. References: 10.1200/JCO.2021.39.3_suppl.9

Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan in Colorectal Cancer with BRAF V600E: R1

Comments changed: Not explicitly excluded by TGA but not recommended by NCCN and ESMO 2016 consensus guidelines..

Tuesday, 20 April 2021 (Version: 20210420AU)

New Trametinib + RMC-4550, SHP099 in Malignant peripheral nerve sheath tumor with NF1 Loss-of-function mutation, deletion: 4

Combined MEK/SHP2 inhibition was shown to be effective in models of NF1-deficient MPNST cell line models. References: 33032988

New SHP099 in Malignant peripheral nerve sheath tumor with NF1 Loss-of-function mutation, deletion: 4

References: 10.1158/1538-7445.AM2020-1889

New Trametinib in Malignant peripheral nerve sheath tumor with NF1+SUZ12 NF1:deletion AND SUZ12:deletion: 4

Case report of an exception responder to trametinib (complete response), with tumour harbouring biallelic deletion of NF1 and SUZ12. References: 33580196

Changed Rucaparib in Pancreatic Adenocarcinoma with BRCA2 Oncogenic mutations

Tier changed: 34.

Changed Rucaparib with BRCA2 Reversion mutations: 4

Cancer type(s) changed: Pancreatic AdenocarcinomaPancreatic cancer

Saturday, 17 April 2021 (Version: 20210417AU)

Friday, 16 April 2021 (Version: 20210416AU)

New Rucaparib in Pancreatic cancer with BRCA2 Reversion mutations: 4

RUCAPANC: two cases of reversion mutations restoring the open reading frame near the germline mutation detected on ctDNA. References: 30051098

New VT3989 in Mesothelioma, Solid tumours with NF2 Oncogenic mutation: 4

References: NCT04665206

New Rucaparib in Ovarian cancer with BRCA1 Reversion mutations: R2

Retrospective cfDNA analysis: platinum-resistant/refractory HGSOC are associated with decreased clinical benefit from rucaparib with significantly reduced mPFS (9.0 vs 1.8 months). References: 30425037

New Rucaparib in Ovarian cancer with BRCA2 Reversion mutations: R2

Retrospective cfDNA analysis: platinum-resistant/refractory HGSOC are associated with decreased clinical benefit from rucaparib with significantly reduced mPFS (9.0 vs 1.8 months). References: 30425037

Wednesday, 14 April 2021 (Version: 20210414AU)

New Pembrolizumab in Breast Cancer with Tumour Mutational Burden High: 3

TAPUR: N=28, HTMB ranging from 9 to 37 mutations/megabase. ORR 21%. Median PFS 10.6 weeks. Both TNBC and non-TNBC were included. References: 33844595

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with PRKDC Oncogenic mutations, Loss-of-function mutation: 4

CT26 animal model with PRKDC-KO showed enhanced efficacy to anti-PD-1 monoclonal antibody. References: 32238472

New Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with PRKDC Oncogenic mutations, Loss-of-function mutation: 4

Retrospective analysis showed that PRKDC mutation is associated with better response to ICI. References: 32502294

New Palbociclib in Non-Small Cell Lung Cancer with SMARCA4 Loss-of-function mutation: 4

SMARCA4 loss is synthetic lethal with palbociclib in NSCLC cell line. References: 30718506

New Palbociclib in Ovarian Small Cell Carcinoma with SMARCA4 Loss-of-function mutation: 4

References: 30718512

Wednesday, 7 April 2021 (Version: 20210407AU)

New Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 Oncogenic mutations (germline): 1

TGA approved. PBS reimbursed. SOLO2 trial. References: 28754483, 33743851

New Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 Oncogenic mutations (germline): 1

TGA approved. PBS reimbursed. SOLO2 trial. References: 28754483, 33743851

New Alpelisib + Fulvestrant in Breast Cancer with PIK3CA E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y: 3

BYLieve single-arm Phase 2 trial. In PIK3CA mutated HR-positive, HER2-negative metastatic breast cancer after CDK4/6 inhibitor therapy, ORR 17%. Median DOR 6.6 months. Median PFS 7.3 mo. References: 33794206

New Ipilimumab + Nivolumab + Carboplatin + Pemetrexed, Ipilimumab + Nivolumab + Cisplatin + Pemetrexed, Ipilimumab + Nivolumab + Carboplatin + Paclitaxel in Non-Small Cell Lung Cancer with Tumour Mutational Burden High: 3

Checkmakte 9LA: In non-EGFR/ALK-altered NSCLC, the prespecified subgroup analysis showed that high tumour TMB (at cut off of 10 mut/MB) is associated with high ORR in the chemo + IO group (46 v 28%), also mPFS (8.9 vs 4.7mo) and OS (15.0 vs 10.8 mo). Similar benefit was was also observed in bTMB at the 16 and 20 mut/MB thresholds. References: 10.1016/S1556-0864(21)01940-7

New Cetuximab, Panitumumab in Colorectal Cancer with BRAF F247L, G466E, G466V, Q524L, R558Q, N581I, N581S, N581T, D594G, D594N, F595L, Class III mutations: 4

Retrospective study. ORR 37% in class III BRAF mutants in third-and-later lines treatment. References: 31515458

New Adagrasib in Non-Small Cell Lung Cancer with KRAS+STK11 KRAS:G12C and STK11:Oncogenic mutations: 4

KRYSTAL-1. Higher ORR was seen in 64% (9/14) with STK11 mutations. References: 10.1016/S1556-0864(21)01941-9

New Cetuximab, Panitumumab in Colorectal Cancer with BRAF G469A, G469V, L485F, L525R, L597R, T599_V600TinsT, K601E, Class II mutations: R2

Retrospective study. ORR 0% in class II BRAF mutants in third-and-later lines treatment. References: 31515458

Changed Brigatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed; FDA approvedTGA approved. Not PBS reimbursed; FDA approved.

Changed BGB659, TAK632, LY3009120 in Solid tumours with BRAF : 4

Alterations changed: Class II mutations, G469A, L597R, K601N.

Changed MEK inhibitor + anti-EGFR monoclonal antibody in Solid tumours with BRAF : 4

Alterations changed: Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R.

Changed RMC-4630 + Cobimetinib in Solid tumours with BRAF : 4

Alterations changed: Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R.

Changed Vemurafenib, Dabrafenib in Solid tumours with BRAF : R2

Alterations changed: Class II mutations, K601E, K601N, K601T, L597Q, L597V, G469A, G469V, G469R, G464V, G464E, Fusions.

Changed PLX8394 in Solid tumours with BRAF : R2

Alterations changed: Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R.

Changed Vemurafenib, Dabrafenib in Solid tumours with BRAF : R2

Alterations changed: Class III mutations, D287H, V459L, G466V, G466E, G466A, S467L, G469E, N581S, N581I, D594N, D594G, D594A, D594H, F595L, G596D, G596R.

Tuesday, 6 April 2021 (Version: 20210406AU)

New Erdafitinib in Non-Small Cell Lung Cancer with FGFR2 FGFR2-BICC1 fusion: 4

Case report showing partial response to erdafitinib. References: 10.1200/PO.20.00110

New Selumetinib in Non-Small Cell Lung Cancer with MAP2K1 K57N, Q56P: 4

Cell line study showing NSCLC cells sensitive to AZD6244. References: 18632602

New Crizotinib in Ovarian cancer with ROS1 Fusion; GOPC-ROS1 Fusion: 4

Case report of high-grade serous ovarian cancer. References: 32652753

New Dabrafenib + Trametinib in Non-Small Cell Lung Cancer with BRAF+KRAS BRAF:V600E AND KRAS:Q61R: R2

References: 32388065

New Dabrafenib + Trametinib in Non-Small Cell Lung Cancer with BRAF+MAP2K1 BRAF:V600E AND MAP2K1:K57N: R2

References: 32388065

New Dabrafenib + Trametinib in Non-Small Cell Lung Cancer with BRAF+NRAS BRAF:V600E AND NRAS:Q61R: R2

References: 32388065

New Dabrafenib + Trametinib in Non-Small Cell Lung Cancer with BRAF+PTEN BRAF:V600E AND PTEN:Oncogenic mutation: R2

References: 32388065

Saturday, 3 April 2021 (Version: 20210403AU)

Thursday, 1 April 2021 (Version: 20210401AU)

New Adavosertib in Uterine Serous Carcinoma with TP53 Oncogenic mutations: 3

Single arm phase II trial with adavosertib in USC with TP53 alterations (predefined hypothesis). ORR 29% with PFS at 6 months 47%. References: 33705205

New Ribociclib + Tamoxifen, Ribociclib + Fulvestrant, Ribociclib + Letrozole, Ribociclib + Anastrozole in Breast Cancer with Intrinsic subtype Luminal A; Luminal B; HER2-enriched; Normal-like: 4

Exploratory analysis from MONALEESA-7, -3, 2 using intrinsic subtype 152 gene expression panel for classification into PAM50-subtypes. Higher ORR was seen in HER2E and LumB subtypes, and PFS benefit was seen in all except Basal subtypes (LumA, LumB, HER2E, and Normal subtypes). References: 33769862

New Ribociclib + Tamoxifen, Ribociclib + Fulvestrant, Ribociclib + Letrozole, Ribociclib + Anastrozole in Breast Cancer with Intrinsic subtype Basal-like: R2

Exploratory analysis from MONALEESA-7, -3, 2 using intrinsic subtype 152 gene expression panel for classification into PAM50-subtypes. No difference in ORR was seen in basal-like molecular subtype (Ribociclib 25 vs Placebo 29%, NS). No difference in was seen in mPFS. References: 33769862

Changed Eprenetapopt + Azacitidine in Myelodysplastic syndrome, Acute myeloid leukaemia with TP53 : 3

Alterations changed: Oncogenic mutations.

Changed Therapy with EGFR Amplification: 4

Therapy changed: FOLFOX + ABT-806, FOLFIRI + Cetuximab, CetuximabABT-806, Cetuximab. Cancer type(s) changed: Gastric cancer, Gastroesophageal junction adenocarcinoma Comments changed: Four of 7 patients with high-level amplification with three complete responses. Minimum EGFR copy number in tissue was 54..

Wednesday, 31 March 2021 (Version: 20210331AU)

New Ipatasertib + Paclitaxel in Breast Cancer with AKT1 Oncogenic mutation: 4

HR-positive disease. IPATunity130 Cohort B. ORR 47% in both ipatasertib and placebo arms but there was no significant difference in median PFS (ipatasertib vs placebo: 9.2 vs 8.5 mo). Ongoing follow-up. References: 10.1016/j.annonc.2020.08.385

New Afatinib in Non-Small Cell Lung Cancer with EGFR L747_A750delinsP: 4

Cell line and in silico structural study demonstrating increased sensitivity to afatinib over erlotinib and osimertinib. References: 31182434

New Afatinib in Non-Small Cell Lung Cancer, Solid tumours with NRG1 Fusion; CD74-NRG1 fusion; POMK-NRG1 fusion; APP-NRG1 fusion: 4

Case series. Partial response seen in patients with fusion in two NSCLC, one colorectal cancer, and one pancreatic cancer treated with afatinib. Two NSCLC patients treated with afatinib were seen with prolonged responses. References: 10.1200/JGO.2019.5.suppl.110

New Afatinib in Non-small cell lung cancer with NRG1 Fusion; CD74-NRG1 fusion; SLC3A2-NRG1 fusion: 4

Case reports. Partial response seen in patients with fusion in two NSCLC with responses of 6 and 10 months respectively. References: 28502724

New Seribantumab in Solid tumours with NRG1 Fusion; CD74-NRG1fusion; VAMP2-NRG1 fusion; SLC3A2-NRG1 fusion: 4

References: 10.1016/S0959-8049(20)31105-9

New Afatinib in Non-small cell lung cancer, Cholangiocarcinoma with NRG1 Fusion; SDC4-NRG1 fusion; ATP1B1-NRG1 fusion: 4

Case reports. Partial response seen in patients with fusion in two NSCLC. References: 28950338

New Lumretuzumab + Erlotinib in Non-small cell lung cancer with NRG1 Fusion; SLC3A2-NRG1 fusion: 4

Case report of invasive mucinous adenocarcinoma of lung. NRG fusion. References: 30268483

New Ipatasertib + Paclitaxel in Breast Cancer with PIK3CA Oncogenic mutation: 4

HR-positive disease. IPATunity130 Cohort B. ORR 47% in both ipatasertib and placebo arms but there was no significant difference in median PFS (ipatasertib vs placebo: 9.2 vs 8.5 mo). Ongoing follow-up. References: 10.1016/j.annonc.2020.08.385

New Ipatasertib + Paclitaxel in Breast Cancer with PTEN Oncogenic mutation: 4

HR-positive disease. IPATunity130 Cohort B. ORR 47% in both ipatasertib and placebo arms but there was no significant difference in median PFS (ipatasertib vs placebo: 9.2 vs 8.5 mo). Ongoing follow-up. References: 10.1016/j.annonc.2020.08.385

New Erlotinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR L747_A750delinsP: R2

Cell line and in silico structural study demonstrating increased sensitivity to afatinib over erlotinib and osimertinib. References: 31182434

Changed Tipifarnib in Head and Neck Squamous Cell Carcinoma, Salivary Gland Cancers, Urothelial Carcinoma with HRAS Oncogenic mutations: 3

Comments changed: Single arm Phase II of Tipifarnib in R/M HNSCC patients. ORR 55%. mPFS tipifarnib: 5.6 months. KO-TIP-001. References changed: 33750196, 10.1200/JCO.2020.38.15_suppl.6504.

Changed BGB659, TAK632, LY3009120 in Solid tumours with BRAF : 4

Alterations changed: G469A, L597R, K601ND287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R. Comments changed: Class II mutation; Sensitive to Group 2 inhibitorsClass III mutation; Sensitive to Group 2 inhibitors.

Changed Therapy in Solid tumours with BRAF D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R: R2

Therapy changed: PLX8394, RAF dimer inhibitor.

Sunday, 28 March 2021 (Version: 20210328AU)

New Enfortumab vedotin in Urothelial Carcinoma with NECTIN4 Protein expression: 4

NECTIN4 mediates sensitivity to enfortumab vedotin, and its downregulation leads to treatment resistance. NECTIN4 is enriched in luminal subtypes of bladder cancer. References: 10.1200/JCO.2021.39.6_suppl.463

Changed Durvalumab in Urothelial Carcinoma with CD274 Protein expression

Tier changed: 31B. Comments changed: TGA conditionally approved but not PBS reimbursed. ORR difference was found between PD-L1 high vs low groups. PD-L1 positivity is defined as >= 25% of either tumour or immune cells staining for PD-L1 using Ventana SP-263 assay. NB: TGA approval was based on response rate. NCT01693562. Note FDA Approval withdrawn in Feb 2021, based on Phase III DANUBE trial results.TGA approved. Not PBS reimbursed. ORR difference between PD-L1 high vs low groups. PD-L1 positivity is defined as >= 25% of either tumour or immune cells staining for PD-L1 using Ventana SP-263 assay. NB: TGA approval was based on response rate. NCT01693562..

Wednesday, 24 March 2021 (Version: 20210324AU)

New Larotrectinib in Oesophageal Squamous Cell Carcinoma with NTRK1 Amplification: 4

Single case report showing partial response to larotrectinib with DOR 3.7 month. References: 32323889

New Gilteritinib in Acute Myeloid Leukaemia with NRAS Q61K, G12C: R2

Mutations in MAPK pathway mediate secondary clinical resistance to FLT3-mutated AML. References: 31088841

New Larotrectinib in Solid tumours with NTRK1 Alterations AND NOT fusion: R2

One of 73 patient with short PR with short direction. References: 10.1158/1538-7445.AM2020-CT062

New Larotrectinib in Solid tumours with NTRK2 Alterations AND NOT fusion: R2

One of 73 patient with short PR with short direction. References: 10.1158/1538-7445.AM2020-CT062

New Larotrectinib in Solid tumours with NTRK3 Alterations AND NOT fusion: R2

One of 73 patient with short PR with short direction. References: 10.1158/1538-7445.AM2020-CT062

Changed Pembrolizumab + Cisplatin + Fluorouracil in Oesophageal Cancer, Oesophageal Adenocarcinoma, Oesophageal Squamous Cell Carcinoma with CD274 Protein expression: 2

Comments changed: Phase 3 KEYNOTE-590. FDA approved 22/03/2021. In the first-line setting, adding pembrolizumab to chemotherapy resulted in superior OS in PD-L1 positive subgroups (defined as CPS ≥ 10%, median 13.5 versus 9.4 mo), but also in ESCC and overall populations. Overall ORR in pembrolizumab arm was 45% (vs control 23%).Phase 3 KEYNOTE-590. FDA approved 22/03/2021. ORR in pembrolizumab arm was 45% (vs control 23%); Superior OS was seen in ESCC, PD-L1 positive (defined as CPS ≥ 10%) but also seen in overall groups..

Tuesday, 23 March 2021 (Version: 20210323AU)

Changed Pembrolizumab + Cisplatin + Fluorouracil in Oesophageal Cancer, Oesophageal Adenocarcinoma, Oesophageal Squamous Cell Carcinoma with CD274 Protein expression: 2

Comments changed: Phase 3 KEYNOTE-590. FDA approved 22/03/2021. ORR in pembrolizumab arm was 45% (vs control 23%); Superior OS was seen in ESCC, PD-L1 positive (defined as CPS ≥ 10%) but also seen in overall groups.Phase 3 KEYNOTE-590. ORR in pembrolizumab arm was 45% (vs control 23%); Superior OS was seen in ESCC, PD-L1 positive (defined as CPS ≥ 10%), and overall groups..

Sunday, 21 March 2021 (Version: 20210321AU)

New Capecitabine + Bevacizumab in Colorectal Cancer with Consensus molecular subtype CMS2, CMS3: 4

MAX: Exploratory analysis showed CMS2 and CMS3 is associated with longer PFS in bevacizumab groups, but not OS. References: 30247524

New FOLFIRI + Cetuximab in Colorectal Cancer with Consensus molecular subtype CMS4: 4

FIRE-3: for RAS wild-type tumours, CMS4 was associated with longer PFS (HR 0.67, p=0.048) and OS (HR 0.57, p=0.008) in Cetuximab versus Bevacizumab in combination with FOLFIRI in the first-line setting. References: 31868905

Friday, 19 March 2021 (Version: 20210319AU)

New Pembrolizumab in Triple-negative breast cancer with CD274 Protein expression: 3

KEYNOTE-119 previously treated TNBC: Single-agent pembrolizumab versus investigator-choice chemotherapy. Failed to meet prespecified primary point of OS (12.7 v 11.6mo) and pre-specified PD-L1 endpoint (as assessed by combined positive score of 1% or greater). However, in the exploratory anaylsis, CPS of 20 or more was associated with higher ORR (26% vs 12%) and OS (14.9 vs 12.5 months). References: 33676601

New Olaparib in Chondrosarcoma with IDH1 R132C, R132S, R132: 3

Phase II Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified. References: 10.1200/PO.20.00247

New Olaparib in Epithelioid haemangioendothelioma with IDH2 V305M: 3

Phase II Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified. References: 10.1200/PO.20.00247

New Olaparib, Veliparib in Solid tumours, Glioma, Glioblastoma, Cholangiocarcinoma with IDH1 R132C, R132H, R132: 4

Cell line study. Mutant IDH cells were demonstrated to be deficient in DNA DSB break repair. References: 28148839, 32494639

New Olaparib, Veliparib in Solid tumours, Glioma, Glioblastoma, Cholangiocarcinoma with IDH2 R172K: 4

Cell line study. Mutant IDH cells were demonstrated to be deficient in DNA DSB break repair. References: 28148839, 32494639

New Olaparib in Cholangiocarcinoma with IDH1 R132C, R132: R2

Phase II Basket trial. Olaparib for IDH mutations. No responders in four cholangiocarcinoma cases (3 cases with R132C). References: 10.1200/PO.20.00247

Thursday, 18 March 2021 (Version: 20210318AU)

New Palbociclib + Avelumab in Solid tumours with CCND1 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CCND2 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CCND3 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CDK4 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CDK6 Amplification: 4

References: ACTRN12620000568910

New Palbociclib + Avelumab in Solid tumours with CDKN2A Oncogenic mutations, deletions, truncating mutations, loss-of-function mutations: 4

References: ACTRN12620000568910

New Ado-Trastuzumab Emtansine in Colorectal Cancer with ERBB2 ERBB2:amplification and KRAS:G12D: 4

Single case report of durable response (15 months) with partial regression of metastases in trastuzumab-resistant disease. References: 32913966

New Lapatinib, Afatinib, Neratinib, Osimertinib in Solid tumours with ERBB2 Extracellular domain mutations; transmembrane domain mutations: 4

High throughput screening of VUS in ERBB2. References: 29967253

New Trastuzumab in Solid tumours with ERBB2 Transmembrane domain mutations: 4

High throughput screening of VUS in ERBB2. References: 29967253

New Ado-Trastuzumab Emtansine in Colorectal Cancer with ERBB2+KRAS ERBB2:amplification and KRAS:G12D: 4

Single case report of clinical response with partial regression of lung metastases (overall stable disease). Post-exposure to trastuzumab and pertuzumab. References: 32023524

New Olaparib in Pancreatic Adenocarcinoma with PALB2 Oncogenic mutations (germline): 4

Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. One responder seen in PALB2 germline mutation. References: 33662100

New Olaparib in Pancreatic Adenocarcinoma with ARID1A Oncogenic mutations: R2

Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. ARID1A (N=3). References: 33662100

New Olaparib in Pancreatic Adenocarcinoma with ATM Oncogenic mutations, Oncogenic mutations (germline): R2

Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. In ATM subgroup, response was seen in 1/14 patients with ATM mutation (somatic). References: 33662100

New Osimertinib in Solid tumours with ERBB2 A775_G776insYVMA: R2

High throughput screening of VUS in ERBB2. References: 29967253

New Ado-Trastuzumab Emtansine + Pertuzumab in Colorectal Cancer with ERBB2 Amplification, Overexpression: R2

Phase II HERACLES-B. N=31. The combination did not reach the primary endpoint (ORR 9.7%), but DCR 77.4% with median PFS 4.1mo. References: 32988996

New Lapatinib in Solid tumours with ERBB2 L755M, L755S, A775_G776insYVMA, G776delinsLC, G776delinsVC, S779_P780insVGS, V842I, T862A: R2

High throughput screening of VUS in ERBB2. References: 29967253

New Trastuzumab in Solid tumours with ERBB2 R487W, L755P, L755S, D769Y, A775_G776insYVMA, G776S, G776V, G776delinsLC, G776delinsVC, V777L, G778_S779insG, P780_Y781insGSP, L841V, V842I, N857S, T862A, D962N, P1199T: R2

High throughput screening of VUS in ERBB2. References: 29967253

New Olaparib in Pancreatic Adenocarcinoma with FANCD2 Oncogenic mutations, Oncogenic mutations (germline): R2

Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. References: 33662100

New Olaparib in Pancreatic Adenocarcinoma with PTEN Oncogenic mutations: R2

Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. PTEN (N=2). References: 33662100

New Olaparib in Pancreatic Adenocarcinoma with RAD51C Oncogenic mutations, Oncogenic mutations (germline): R2

Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. References: 33662100

Changed PARP inhibitor in Solid tumours with BARD1 Oncogenic mutations: 4

References changed: 30925164, 27197561, NCT02401347, NCT02489006, NCT02760849, NCT02952534, NCT02993068, NCT03207347, NCT03377556, NCT03495544, NCT03786796, NCT04171700, NCT04190667, NCT0427637630925164, 27197561, NCT02401347, NCT02401347, NCT02489006, NCT02760849, NCT02952534, NCT02993068, NCT03207347, NCT03377556, NCT03495544, NCT03786796, NCT04171700, NCT04190667, NCT04276376.

Changed Venetoclax with BCL2 Amplification: 4

Cancer type(s) changed: Non-Small Cell Lung Cancer Comments changed: Downgraded; Preclinical data only.

Changed Erdafitinib in Solid tumours with FGFR3 Amplification, Fusion, Oncogenic mutation and NOT V565 and NOT V550: 4

Comments changed: NCT01703481, Phase I dose escalation and expansion. ORR 46% in urothelial carcinoma and 27% in cholangiocarcinoma. <10% for the rest of tumour types.NCT01703481, ORR 46.2%.

Changed Crizotinib with ALK G1128A, E1129V, L1122V, C1156Y, D1160H, F1174, R1192P, L1196M, L1198F, G1202R, G1269A: R2

Cancer type(s) changed: Non-Small Cell Lung Cancer

Changed Palbociclib in Pancreatic Adenocarcinoma, Cholangiocarcinoma, Gallbladder Cancer with CDKN2A : R2

Alterations changed: Loss-of-function mutation, oncogenic mutations. Comments changed: TAPUR. N=20. ORR and DCR 0%.. References changed: 10.1200/PO.19.0012425524798.

Tuesday, 16 March 2021 (Version: 20210316AU)

New Talazoparib in Lung Squamous Cell Carcinoma with ATM Oncogenic mutation: R2

Lung-MAP Substudy S1400G. ORR primary population 4%. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with ATR Oncogenic mutation: R2

Lung-MAP Substudy S1400G. ORR primary population 4%. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with BRCA1 Oncogenic mutation: R2

Lung-MAP Substudy S1400G. ORR primary population 4%. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with BRCA2 Oncogenic mutation: R2

Lung-MAP Substudy S1400G. ORR primary population 4%. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with PALB2 Oncogenic mutation: R2

Lung-MAP Substudy S1400G. ORR primary population 4%. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with BRCA2 Oncogenic mutation: 4

Lung-MAP Substudy S1400G. Responder in Full eligible population. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with FANCM Oncogenic mutation: 4

Lung-MAP Substudy S1400G. 3 responders in Full eligible population. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with FANCC Oncogenic mutation: 4

Lung-MAP Substudy S1400G. Responder in Full eligible population. References: 33583720

New Talazoparib in Lung Squamous Cell Carcinoma with CHEK1 Oncogenic mutation: 4

Lung-MAP Substudy S1400G. Responder in Full eligible population. References: 33583720

Removed Selumetinib in Type 1 neurofibromatosis with NF1 alterations Oncogenic mutations (germline): Tier 2

Changed Selumetinib with NF1 Oncogenic mutations (germline): 2

Cancer type(s) changed: Gliomas, Paediatric low grade gliomas, Type 1 neurofibromatosis

Friday, 12 March 2021 (Version: 20210312AU)

New Afatinib in Non-Small Cell Lung Cancer with ERBB2 Exon 16 skipping mutation: 4

References: 31557536

New Pembrolizumab, Atezolizumab, Nivolumab, Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-Small Cell Lung Cancer with ALK Fusion: R2

IMMUNOTARGET registry. References: 31125062

New Osimertinib in Non-Small Cell Lung Cancer with EGFR Amplification: R2

Cell line data. Wild type EGFR. References: 28202511

New Pembrolizumab, Atezolizumab, Nivolumab, Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-Small Cell Lung Cancer with EGFR Oncogenic mutation: R2

Meta-analysis of five clinical trials suggest that immune check point blockades confers no survival benefit as second-line therapy. References: 29270615

New Osimertinib in Non-Small Cell Lung Cancer with ERBB2 Exon 16 skipping mutation: R2

In EGFR L858R/T790M-positive lung adenocarcinoma who developed resistance to osimertinib through an Src-independent pathway. References: 31557536, 33209639

New Osimertinib in Non-Small Cell Lung Cancer with KRAS G12S: R2

Secondary resistance post Osimertinib. References: 27252416

New Osimertinib in Non-Small Cell Lung Cancer with KRAS G13D: R2

Cell line data. Off-target resistance. References: 28202511

New Osimertinib in Non-Small Cell Lung Cancer with MET Amplification: R2

Secondary resistance post Osimertinib. Amplification determined by FISH. References: 27252416

New Osimertinib in Non-Small Cell Lung Cancer with PIK3CA G118D: R2

Cell line data. Off-target resistance. References: 28202511

Changed Pembrolizumab in Non-Small Cell Lung Cancer with CD274 Protein expression: 1

Comments changed: PBS reimbursed. TGA approved as monotherapy for the first-line treatment of patients with NSCLC expressing PD-L1, and EGFR and ALK negative. Defined as tumour proportion score (TPS) greater than or equal to 1%. KEYNOTE 042 and KEYNOTE-024.PBS reimbursed. TGA approved as monotherapy for the first-line treatment of patients with NSCLC expressing PD-L1. Defined as tumour proportion score (TPS) greater than or equal to 1%. KEYNOTE 042 and KEYNOTE-024..

Changed Pembrolizumab in Non-Small Cell Lung Cancer with CD274 Protein expression: 1

Comments changed: PBS reimbursed. TGA approved as monotherapy for the subsequent-line treatment of patients with NSCLC expressing PD-L1 (defined as tumour proportion score (TPS) greater than or equal to 1%), and EGFR and ALK negative. KEYNOTE-010PBS reimbursed. TGA approved as monotherapy for the subsequent-line treatment of patients with NSCLC expressing PD-L1 (defined as tumour proportion score (TPS) greater than or equal to 1%). KEYNOTE-010.

Changed Atezolizumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion: 1B

Comments changed: TGA approved; IMPower110: First-line treatment in PD-L1 positive population (defined as positive stain on >=least 1% of tumour cells or tumor-infiltrating immune cells >= 1% of the tumor area), EGFR and ALK negative. Median OS: 20 vs 13 months (chemotherapy)TGA approved; IMPower110: First-line treatment in PD-L1 positive population (defined as positive stain on >=least 1% of tumour cells or tumor-infiltrating immune cells >= 1% of the tumor area). Median OS: 20 vs 13 months (chemotherapy).

Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion: 1B

Comments changed: TGA approved; FDA approved; Checkmate 227. PD-L1 positivity defined as >= 1% of tumour cells using Dako 28-8 pharmDx assay. EGFR and ALK negative.

Changed Cemiplimab in Non-Small Cell Lung Cancer with CD274 Protein expression: 2

Comments changed: Not TGA approved. FDA Approved. EMPOWER-Lung 1: As first-line treatment, cemiplimab resulted in median PFS of 8.2 (vs 5.7 mo chemotherapy, HR 0.54) in patients with PD-L1 expression (Tumour proportion score) >= 50% as determined by the 22C3 PharmDx assay. EGFR, ALK, and ROS1 negative population. Duration and depth of response correlate to PD-L1 TPS.Not TGA approved. FDA Approved. EMPOWER-Lung 1: As first-line treatment, cemiplimab resulted in median PFS of 8.2 (vs 5.7 mo chemotherapy, HR 0.54) in patients with PD-L1 expression (Tumour proportion score) >= 50% as determined by the 22C3 PharmDx assay. Duration and depth of response correlate to PD-L1 TPS..

Wednesday, 10 March 2021 (Version: 20210310AU)

New Crizotinib, Foretinib in Breast Cancer with CDH1 Loss-of-function mutation: 4

ROS1 inhibitors create synthetic lethality in CDH1 deficient breast cancer cell lines. References: 29610289

Changed Tepotinib in Non-Small Cell Lung Cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. VISION trial. ORR 48%. All lines of therapy..

Tuesday, 9 March 2021 (Version: 20210309AU)

Removed Seribantumab in Solid tumours with NRG1 alterations Fusion: Tier 4

Changed Pembrolizumab, Atezolizumab, Nivolumab + Ipilimumab, Durvalumab + Tremelimumab in Prostate cancer with CDK12 : 4

Alterations changed: Loss-of-function mutationOncogenic mutation.

Changed Therapy in Solid tumours with NRG1 Fusion: 4

Therapy changed: ZenocutuzumabMCLA-128.

Changed Olaparib in Prostate cancer with CDK12 : R2

Alterations changed: Loss-of-function mutationsOncogenic mutation.

Monday, 8 March 2021 (Version: 20210308AU)

New Poziotinib in Solid tumours, Non-Small Cell Lung Cancer with ERBB2 A775_G776insYVMA, G778_P780dup: 3

Phase II. ORR 43% (5/12) and DCR 83%. NCT03066206. References: 31588020

New Dacomitinib in Non-Small Cell Lung Cancer with ERBB2 G778_P780dup: 3

Phase II trial: 2/2 patients harbouring the mutation responded to Dacomitinib with prolonged response. References: 25899785

New Anlotinib in Glioblastoma with FGFR3 FGFR3-TACC3 fusion: 4

Case report. References: 32949176

New Dacomitinib in Non-Small Cell Lung Cancer with ERBB2 A775_G776insYVMA: R2

No partial response observed in thirteen patients. References: 25899785

New Crizotinib in Non-Small Cell Lung Cancer with ROS1+MET ROS1:fusion AND MET:D1228N: R2

Case report. References: 33000474

Removed ERBB2 inhibitor,exon 20 selective in Solid tumours with ERBB2 alterations Exon 20 mutation, Exon 20 insertion: Tier 4

Changed Therapy in Non-Small Cell Lung Cancer with EGFR Exon 20 insertion: 3

Therapy changed: MobocertinibTAK-788. Comments changed: NCT02716116: Phase 1/2 trial. 28 / 136 patient had exon 20 insertion. ORR to TAK-788 was 43%.AACR 2020. References changed: 33632775NCT02716116.

Sunday, 7 March 2021 (Version: 20210307AU)

New Afatinib in Non-Small Cell Lung Cancer with ERBB2 A775_G776insYVMA: 4

1 PR and 2SD in retrospective case series. References: 23610105

New Afatinib in Non-Small Cell Lung Cancer with ERBB2 A775_G776insYVMA, G778_P780dup, G776: 4

Case series. References: 22325357

New Afatinib in Lung adenocarcinoma with ERBB2 Oncogenic mutation: 4

One unconfirmed response from seven patients (5 SD). Individual and concomitant mutations not reported. References: 25682316

New Afatinib in Lung Squamous Cell Carcinoma with ERBB2 Q57R, S250C, E265K, E395K, G815R: 4

Retrospective analysis from LUX-8. However, unable to distinguish response to treatment with afatinib or tumour biology of disease. References: 29902295

Saturday, 6 March 2021 (Version: 20210306AU)

New CX-5461, CX-5461 + Olaparib in Ovarian cancer with BRCA1 Oncogenic mutation: 4

Combination of RNA polymerase I and PARP inhibitors showed synergy in Xenograft and cell line models of HR-deficient high-grade serous ovarian cancers. References: 32457376

New CX-5461, CX-5461 + Olaparib in Ovarian cancer with BRCA2 Oncogenic mutation: 4

Combination of RNA polymerase I and PARP inhibitors showed synergy in Xenograft and cell line models of HR-deficient high-grade serous ovarian cancers. References: 32457376

New CX-5461 in Neuroblastoma with MYC Amplification, Overexpression: 4

Xenograft model established on KELLY cell line CX-5461 leads to MYCN downregulation and suppress orthotopic tumour growth. References: 30879743

New CX-5461 in Neuroblastoma with MYCN Amplification, Overexpression: 4

Xenograft model established on KELLY cell line CX-5461 leads to MYCN downregulation and suppress orthotopic tumour growth. References: 30879743

New CX-5461, Halofuginone in Neuroblastoma with MYCN Amplification, Overexpression: 4

Both Halofuginone and CX-5461 suppressed neuroblastoma in vitro, most notably in MYCN amplified and TP53 wildtype cell-line. References: 29464082

Removed Nivolumab in Non-small cell lung cancer with CD274 alterations Protein expression: Tier 3

Removed immune checkpoint blockade,PD-L1 targeting in Solid tumours with CD274 alterations Amplification: Tier 4

Changed Camrelizumab in Oesophageal Squamous Cell Carcinoma with CD274 Protein expression: 3

Comments changed: Subgroup analysis showed that PD-L1 positive subgroup (defined as TPS >= 1%) derives more benefitsExploratory subgroup PD-L1 positive.

Changed Therapy in Solid tumours with CD274 Amplification: 4

Therapy changed: Anti-PD-1 monoclonal antibody, immune checkpoint blockade,PD-L1 targeting. References changed: 27900363; 27942391; 29902298; 10.1200/PO.18.00017.

Changed Toripalimab in Gastric cancer with CD274 Protein expression: 4

Comments changed: ORR 37% in tumours with PD-L1 expression >= 1% for TC or IC using SP142 assay (v 8%).ORR 37 v 8% in tumour cell. SP142. Cutoff 1%.

Changed Nivolumab in Non-Small Cell Lung Cancer with Tumour Mutational Burden High: 4

Comments changed: Exploratory analysis from Checkmate 026. High TMB was defined as highest third of mutations in the study cohort..

Changed Pembrolizumab in Cervical cancer with CD274 Loss of protein expression: R2

Comments changed: KEYNOTE-028. ORR 0% in PD-L1 negative population (CPS < 1%)..

Friday, 5 March 2021 (Version: 20210305AU)

Removed Neratinib in Breast Cancer with ERBB2 alterations Amplification: Tier 2

Changed Pembrolizumab in Cervical cancer with CD274 Protein expression: 2

Comments changed: Not TGA approved. KEYNOTE-028: Phase 1b. ORR 17%. KEYNOTE-158: ORR 15%. PD-L1 positivity defined as CPS >= 1% (22C3 pharmDx assay).Not TGA approved. KEYNOTE-028 and 158.

Changed Nivolumab + FOLFOX, Nivolumab + CAPOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CD274 Protein expression: 2

Comments changed: Not TGA approved. CheckMate 649: Phase III, First-line, HER2-negative gastric/GOJ carcinoma. PD-L1 positivity defined as CPS ≥ 5%CheckMate 649 study. CPS more than 5.

Changed Pembrolizumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with CD274 Protein expression: 2

Comments changed: Not TGA approved. FDA approved. KEYNOTE-059: Phase 2 single arm study in previously treated disease. ORR 16% in PD-L1 positivity (defined as CPS >= 1%, 22C3 pharmDx assay). DOR: 16.3 months..

Changed Pembrolizumab + Cisplatin + Fluorouracil in Oesophageal Cancer, Oesophageal Adenocarcinoma, Oesophageal Squamous Cell Carcinoma with CD274 Protein expression: 2

Comments changed: Phase 3 KEYNOTE-590. ORR in pembrolizumab arm was 45% (vs control 23%); Superior OS was seen in ESCC, PD-L1 positive (defined as CPS ≥ 10%), and overall groups.KEYNOTE-590. CPS cutoff 10.

Changed Pembrolizumab in Oesophageal squamous cell carcinoma with CD274 Protein expression: 2

Comments changed: Not TGA approved. Not PBS reimbursed. KEYNOTE-181: superior OS in Pembrolizumab arm. PD-L1 positive (defined as CPS ≥ 10%), and overall groups.. References changed: 33026938, 10.1200/JCO.2019.37.4_suppl.2.

Changed Pembrolizumab + Nab-paclitaxel, Pembrolizumab + Paclitaxel, Pembrolizumab + Carboplatin + Gemcitabine in Triple-negative Breast Cancer with CD274 Protein expression: 2

Comments changed: Not TGA approved. FDA accelerated approval. KEYNOTE-355: First-line pembrolizumab combination with chemotherapy in TNBC with PD-L1 expression (defined as combined positive score of >= 10%). PFS 9.7 v 5.6mo.First line with chemotherapy. References changed: 33278935, 10.1200/JCO.2020.38.15_suppl.1000.

Changed Avelumab in Urothelial Carcinoma with CD274 Protein expression: 2

Comments changed: Not TGA approved. FDA Approved. JAVELIN Bladder 100: Maintenance therapy after response to first-line platinum therapy. PD-L1 status is determined by SP263 assay and is considered positive if >=25% TC positive, >=25% IC positive with >= 1% TC positive, or 100% IC if <1% TC positive. PFS 5.7 vs 2.1 months, and OS NE vs 17.1 months, in PD-L1 positive population (vs best supportive care). In PD-L1 negative group, there was also PFS benefit shown but no OS improvement over best supportive care.Not TGA approved. FDA Approved. JAVELIN Bladder 100. Maintenance. PD-L1 negative group also has benefit but less in magnitude..

Changed Capecitabine + Trastuzumab + Tucatinib in Breast Cancer with ERBB2 Amplification: 2

Comments changed: Not TGA approved; FDA approved; HER2Climb: PFS: 7.8 (tucatinib) v 5.6 (placebo) months and OS 21.9 v 17.4 month..

Changed Fam-trastuzumab deruxtecan-nxki in Breast Cancer with ERBB2 : 2

Alterations changed: Amplification; Overexpression. Comments changed: Not TGA approved. FDA approved. DESTINY-Breast01: In patients with prior anti-HER2 therapies, median DOR 14.8mo, PFS 16.4mo. HER2 positivity: defined as IHC 3+ or FISH positive..

Changed Lapatinib + Trastuzumab in Breast Cancer with ERBB2 Amplification: 2

Comments changed: Not TGA approved. Upon progression of trastuzumab-containing specimens..

Changed Neratinib + Capecitabine in Breast Cancer with ERBB2 Amplification: 2

Comments changed: Not TGA approved. FDA approved. NALA: Phase III trial in patient previously treated with two or more lines of HER2-directed regimens, median PFS of neratinib was superior over lapatinib.Not TGA approved. FDA approved. NALA. PFS superior over lapatinib.

Changed Margetuximab + Capecitabine, Margetuximab + Eribulin, Margetuximab + Gemcitabine, Margetuximab + Vinorelbine in Breast Cancer with ERBB2 Amplification; Overexpression: 2

Comments changed: Not TGA approved. FDA approval for margetuximab and chemotherapy combination.

Changed Fam-trastuzumab deruxtecan-nxki in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression: 2

Comments changed: Not TGA approved. FDA approved. DESTINY-Gastric01. No response in patients with HER2 ISH+ and IHC 2+Not TGA approved. FDA approved. DESTINY-Gastric01, No response if ISH+ and HER2 2+.

Changed Veliparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with Homologous Recombination Deficiency Score High: 2

Comments changed: Not TGA approved. PFS 31.9 vs 20.5 months in the HRD cohort. HRD positivity is defined as HRD score >= 33 on myChoice CDx assay..

Changed Capmatinib in Non-Small Cell Lung Cancer with MET Amplification, Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 2

Comments changed: Not TGA approved; FDA approved; GEOMETRY mono-1: In MET amplified group (defined as gene copy number, GCN, >= 10), ORR 29% (previously treated) versus 40% (previously untreated). Limited response were seen with GCN <10 (ORR 7-12%)..

Changed Nivolumab in Colorectal Cancer with Microsatellite Instability High: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. ORR 31%, DCR 69% at 12 weeks..

Changed Nivolumab in Colorectal Cancer with Mismatch repair Deficient: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. ORR 31%, DCR 69% at 12 weeks..

Changed Taselisib + Fulvestrant in Breast Cancer with PIK3CA Oncogenic mutations: 2

Comments changed: Not TGA approved. Not FDA approved. Positive Phase III SANDPIPER with regards to median PFS (7.4 months) over placebo (5.4 mo). However, taselisib has limited clinical utility given safety profile and low magnitude of clinical benefit.Phase III SANDPIPER. No formal publication yet. References changed: 33186740, 10.1200/JCO.2018.36.18_suppl.LBA1006.

Changed Ipatasertib + Abiraterone in Prostate cancer with PTEN Loss of protein expression; Loss-of-function mutation: 2

Comments changed: Not TGA approved. IPATential150. Predefined NGS concordant with IHC..

Thursday, 4 March 2021 (Version: 20210304AU)

New Pembrolizumab in Colorectal Cancer with Mismatch repair Deficient: 1B

TGA approved. KEYNOTE-164: Previously treated. ORR 33%. Median OS 31.4mo. MSI-H defined as PCR-based analysis of microsatellite loci by local testing. References: 31725351

New Pembrolizumab in Solid tumours with Mismatch repair Deficient: 1B

TGA provisional approval for MSI-H/dMMR. FDA approved. ORR 34%. KEYNOTE-158: Median PFS 4.1months. Median OS 23.5 months. References: 26028255, 31682550, 10.1158/1078-0432.CCR-18-4070

New Lorlatinib in Non-Small Cell Lung Cancer with ALK G1202R, G1202del, F1174, L1196M, G1269A, I1171: 3

Loratinib has activities in patients who developed acquired resistance to first and second generation TKIs. ORR 42-89% across the list of mutations. References: 30892989

New Crizotinib in Neuroblastoma with ALK R1275Q: 3

Phase 2 study. ADVL0912. ORR 15%. References: 33568345

New Crizotinib in Neuroblastoma with ALK F1174L, Amplification: R2

Phase 2 study. ADVL0912. References: 33568345

New Crizotinib in with ALK G1128A, E1129V, L1122V, C1156Y, D1160H, F1174, R1192P, L1196M, L1198F, G1202R, G1269A: R2

Resistance listed for groups EXP2/EXP3A (crizotinib) only. For EXP(3B-5), exposure to individual drugs was not detailed in the publication. References: 30892989

Removed Olaparib + Bevacizumab in Ovarian Cancer; Peritoneal Serous Carcinoma; Fallopian Tube Carcinoma with BRCA1 alterations Oncogenic mutations: Tier 1B

Removed Olaparib + Bevacizumab in Ovarian Cancer; Peritoneal Serous Carcinoma; Fallopian Tube Carcinoma with BRCA2 alterations Oncogenic mutations: Tier 1B

Removed Pembrolizumab in Solid tumours with MLH1 alterations Loss of protein expression: Tier 1B

Removed Pembrolizumab in Solid tumours with MSH2 alterations Loss of protein expression: Tier 1B

Removed Pembrolizumab in Solid tumours with MSH6 alterations Loss of protein expression: Tier 1B

Removed Pembrolizumab in Solid tumours with PMS2 alterations Loss of protein expression: Tier 1B

Removed Veliparib in Ovarian Cancer; Peritoneal Serous Carcinoma; Fallopian Tube Carcinoma with BRCA1 alterations Oncogenic mutations (germline): Tier 2

Removed Cemiplimab in Non-Small Cell Lung Cancer with CD274 alterations Protein expression: Tier 2

Removed Ipilimumab + Nivolumab in Colorectal Cancer with MLH1 alterations Loss of protein expression: Tier 2

Removed Nivolumab in Colorectal Cancer with MLH1 alterations Loss of protein expression: Tier 2

Removed Ipilimumab + Nivolumab in Colorectal Cancer with MSH2 alterations Loss of protein expression: Tier 2

Removed Nivolumab in Colorectal Cancer with MSH2 alterations Loss of protein expression: Tier 2

Removed Ipilimumab + Nivolumab in Colorectal Cancer with MSH6 alterations Loss of protein expression: Tier 2

Removed Nivolumab in Colorectal Cancer with MSH6 alterations Loss of protein expression: Tier 2

Removed Ipilimumab + Nivolumab in Colorectal Cancer with PMS2 alterations Loss of protein expression: Tier 2

Removed Nivolumab in Colorectal Cancer with PMS2 alterations Loss of protein expression: Tier 2

Removed Everolimus in Subependymal giant cell astrocytoma with TSC1 alterations Oncogenic mutations (germline): Tier 2

Removed Everolimus in Subependymal giant cell astrocytoma with TSC2 alterations Oncogenic mutations (germline): Tier 2

Changed Midostaurin in Acute Myeloid Leukaemia with FLT3 Internal tandem duplication, Kinase domain mutation: 1

Comments changed: TGA approved. PBS reimbursed. Maintenance treatment as a single-agent.TGA approved. PBS reimbursed. Single agent maintenance.

Changed Lanreotide in Pancreatic neuroendocrine tumour, neuroendocrine tumour with SSTR2 Protein expression: 1

Comments changed: PBS reimbursed. CLARINET. Well-to-moderately-differentiated with a positive Octreotide scan..

Changed Octreotide in Pancreatic neuroendocrine tumour, neuroendocrine tumour with SSTR2 Protein expression: 1

Comments changed: PBS reimbursed. PROMID trial. Well-differentiated metastatic midgut tumors. No significant OS differences between treatment arms due to cross-over.PBS reimbursed. PROMID trial. No significant OS differences between treatment arms due to cross-over.. References changed: 19704057, 26731483.

Changed Everolimus in Solid tumours, Subependymal giant cell astrocytoma with TSC1 Oncogenic mutations (germline): 1

Comments changed: PBS reimbursed. SEGA or visceral tumours in patients with tuberous sclerosis complex. EXIST-1.. References changed: 23158522, 23325902.

Changed Everolimus in Solid tumours, Subependymal giant cell astrocytoma with TSC2 Oncogenic mutations (germline): 1

Comments changed: PBS reimbursed. SEGA or visceral tumours in patients with tuberous sclerosis complex. EXIST-1.. References changed: 23158522, 23325902.

Changed Bosutinib in Chronic Myelogenous Leukaemia with ABL1 BCR-ABL1 Fusion: 1B

Comments changed: TGA approved. Not PBS reimbursed. Third or later line treatment. BFORE trial.TGA approved. Not PBS reimbursed. Third line treatment or later.

Changed Niraparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 Oncogenic mutations: 1B

Comments changed: TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012..

Changed Olaparib in Breast Cancer with BRCA1 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. OlympiAd..

Changed Talazoparib in Breast Cancer with BRCA1 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. EMBRACA trial..

Changed Niraparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 Oncogenic mutations: 1B

Comments changed: TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012..

Changed Olaparib in Breast Cancer with BRCA2 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. OlympiAd..

Changed Talazoparib in Breast Cancer with BRCA2 Oncogenic mutations (germline): 1B

Comments changed: TGA approved. Not PBS reimbursed. EMBRACA trial..

Changed Ibrutinib in Non-Hodgkin’s Lymphoma with CD20 Protein expression: 1B

Comments changed: TGA approved for 1+ prior therapy with an anti-CD20 antibody-containing regimen..

Changed Atezolizumab + nab-Paclitaxel in Triple-negative breast cancer with CD274 Protein expression: 1B

Comments changed: TGA provisional approval based on PFS data. Not PBS reimbursed. IMpassion130. PD-L1 positive is defined as >= 1% immune cells as percentage of tumour area. (IC1/2/3).TGA approved (provisional). Not PBS reimbursed.

Changed Atezolizumab in Urothelial carcinoma with CD274 Protein expression: 1B

Comments changed: TGA approved. Not PBS reimbursed. IMVigor211. PD-L1 positivity defined as stained tumour-infiltrating immune cells covering >= 5% of the tumour area. (IC2 or IC3).

Changed Durvalumab in Urothelial Carcinoma with CD274 Protein expression: 1B

Comments changed: TGA approved. Not PBS reimbursed. ORR difference between PD-L1 high vs low groups. PD-L1 positivity is defined as >= 25% of either tumour or immune cells staining for PD-L1 using Ventana SP-263 assay. NB: TGA approval was based on response rate. NCT01693562.TGA approved. Not PBS reimbursed. ORR difference between PD-L1 high vs low groups. Note approval based on response rate of Ph1/2 data. NCT01693562..

Changed Atezolizumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion: 1B

Comments changed: TGA approved; IMPower110: First-line treatment in PD-L1 positive population (defined as positive stain on >=least 1% of tumour cells or tumor-infiltrating immune cells >= 1% of the tumor area). Median OS: 20 vs 13 months (chemotherapy)TGA approved; IMPower110; 1L treatment. PD-L1 positive. Median OS: 20 vs 13 months (chemotherapy).

Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion: 1B

Comments changed: TGA approved; FDA approved; Checkmate 227. PD-L1 positivity defined as >= 1% of tumour cells using Dako 28-8 pharmDx assay..

Changed Lapatinib + Paclitaxel in Breast Cancer with ERBB2 Amplification: 1B

Comments changed: TGA approved. Not PBS reimbursed. NCT00281658: HER2 positivity determined by FISH..

Changed Lapatinib + Letrozole in Breast Cancer with ERBB2 : 1B

Alterations changed: Amplification, Overexpression. Comments changed: TGA approved. Not PBS reimbursed. HER2 positivity is defined as IHC 3+ or IHC 2+/FISH positive. NCT00073528..

Changed Ripretinib in Gastrointestinal Stromal Tumour with KIT Protein expression; Oncogenic mutations: 1B

Comments changed: TGA approved for patients with GIST who received prior treatment with 3 or more kinase inhibitors; Not PBS Reimbursed.TGA approved; Not PBS Reimbursed.

Changed Pembrolizumab in Colorectal Cancer with Microsatellite Instability High: 1B

Comments changed: TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, the PFS was not significantly different. MSI-H defined as PCR-based analysis of 3-5 tumor microsatellite loci by local testing.TGA provisionally approved for MSI-H/dMMR. KEYNOTE-177. PFS v chemotherapy: 16.5 vs. 8.2 months. Note KRAS mutant subgroup PFS NS..

Changed Pembrolizumab with Microsatellite Instability High: 1B

Cancer type(s) changed: Colorectal CancerSolid tumours Comments changed: TGA approved. KEYNOTE-164: Previously treated. ORR 33%. Median OS 31.4mo. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.TGA provisional approval for MSI-H/dMMR. FDA approved. References changed: 3172535130787022, 10.1158/1078-0432.CCR-18-4070.

Changed Pembrolizumab in Solid tumours: 1B

Biomarker changed: Microsatellite InstabilityMismatch repair. Alterations changed: HighDeficient. Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approved. ORR 34%. Median PFS 4.1months. Median OS 23.5 months..

Changed Pembrolizumab in Colorectal Cancer with Mismatch repair Deficient: 1B

Comments changed: TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, the PFS was not significantly different. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.TGA provisionally approved for MSI-H/dMMR. KEYNOTE-177. PFS v chemotherapy: 16.5 vs. 8.2 months. Note KRAS mutant subgroup PFS NS..

Changed Larotrectinib in Solid tumours with NTRK1 : 1B

Alterations changed: Fusions, ATP1A4-NTRK1 fusion, CD74-NTRK1 fusion, CTRC-NTRK1 fusion, DDR2-NTRK1 fusion, DIAPH1-NTRK1 fusion, EPS15-NTRK1 fusion, GON4L-NTRK1 fusion, IRF2BP2-NTRK1 fusion, LMNA-NTRK1 fusion, NFASC-NTRK1 fusion, PDE4DIP-NTRK1 fusion, PLEKHA6-NTRK1 fusion, PPL-NTRK1 fusion, SQSTM1-NTRK1 fusion, TPM3-NTRK1 fusion, TPR-NTRK1 fusion, TRIM63-NTRK1 fusion. Comments changed: TGA approved. Not PBS reimbursed. NCT02122913, NCT02637687, NCT02576431.

Changed Entrectinib in Solid tumours with NTRK1 : 1B

Alterations changed: Fusions, CD74-NTRK1 fusion, CDC42BPA-NTRK1 fusion, CGN-NTRK1 fusion, EPS15L1-NTRK1 fusion, ERC1-NTRK1 fusion, LMNA-NTRK1 fusion, PDIA3-NTRK1 fusion, PEAR1- NTRK1 fusion, PLEKHA6-NTRK1 fusion, SQSTM1-NTRK1 fusion, TPM3-NTRK1 fusion, TPR-NTRK1 fusion, TRIM33- NTRK1 fusion. Comments changed: TGA approved. Not PBS reimbursed. ALKA-372-001, STARTRK-1, and STARTRK-2 trials..

Changed Larotrectinib in Solid tumours with NTRK2 : 1B

Alterations changed: Fusions, GNAQ-NTRK2 fusion, RBPMS-NTRK2 fusion, STRN-NTRK2 fusion, TRAF2-NTRK2 fusion. Comments changed: TGA approved. Not PBS reimbursed. NCT02122913, NCT02637687, NCT02576431.

Changed Entrectinib in Solid tumours with NTRK2 : 1B

Alterations changed: Fusions, SQSTM1-NTRK2 fusion. Comments changed: TGA approved. Not PBS reimbursed. ALKA-372-001, STARTRK-1, and STARTRK-2 trials..

Changed Entrectinib in Solid tumours with NTRK3 : 1B

Alterations changed: Fusions, AKAP13-NTRK3 fusion, EML4-NTRK3 fusion, ETV6-NTRK3 fusion, FAM19A2-NTRK3 fusion, KIF7-NTRK3 fusion, RBPMS-NTRK3 fusion. Comments changed: TGA approved. Not PBS reimbursed. ALKA-372-001, STARTRK-1, and STARTRK-2 trials..

Changed Larotrectinib in Solid tumours with NTRK3 : 1B

Alterations changed: Fusions, ARNT2-NTRK3 fusion, EML4-NTRK3 fusion, ETV6-NTRK3 fusion, IQGAP1-NTRK3 fusion, MYO5A-NTRK3 fusion, SPECC1L-NTRK3 fusion, SQSTM1-NTRK3 fusion, TFG-NTRK3 fusion, TPM4-NTRK3 fusion. Comments changed: TGA approved. Not PBS reimbursed. NCT02122913, NCT02637687, NCT02576431.

Changed Ripretinib in Gastrointestinal Stromal Tumour with PDGFRA Oncogenic mutations: 1B

Comments changed: TGA approved; FDA approved; Note PDGFRA was specified group in original trial, but only 3 cases were included in INVICTUS.TGA approved; FDA approved; NB Pre-specified group in original trial, but only 3 cases were included in INVICTUS..

Changed Crizotinib in Anaplastic Large Cell Lymphoma with ALK : 2

Alterations changed: Fusions, EML4-ALK FusionEML4-ALK Fusion, Fusions. Comments changed: Not TGA approved; FDA approved..

Changed Crizotinib in Inflammatory Myofibroblastic Tumour with ALK : 2

Alterations changed: Fusions, RANBP2-ALK Fusion. Comments changed: Not TGA approved..

Changed Atezolizumab + Cobimetinib + Vemurafenib in Melanoma with BRAF V600E: 2

Comments changed: Not TGA approved.

Changed Olaparib in Prostate cancer with BRCA1 Oncogenic mutations: 2

Comments changed: Not TGA Approved. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). FoundationOne CdxNot TGA Approved. PROFOUND trial..

Changed Olaparib in Pancreatic Adenocarcinoma with BRCA1 Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. POLO trial..

Changed Olaparib + Bevacizumab in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 : 2

Alterations changed: Oncogenic mutations, Oncogenic mutations (germline). Comments changed: Combination not TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX.Not TGA approved; FDA Approved PAOLA-1; Platinum-sensitivity not yet listed as marker.

Changed Veliparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 : 2

Alterations changed: Oncogenic mutations, Oncogenic mutations (germline).

Changed Rucaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 : 2

Alterations changed: Oncogenic mutations, Oncogenic mutations (germline), M1V, M1I, C61G, C64Y, R71G, R71K, R1495M, E1559K, D1692N, D1692H, R1699W, A1708E, G1788V.

Changed Olaparib in Prostate cancer with BRCA2 Oncogenic mutations: 2

Comments changed: Not TGA Approved. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control).Not TGA Approved. PROFOUND trial..

Changed Olaparib in Pancreatic Adenocarcinoma with BRCA2 Oncogenic mutations (germline): 2

Comments changed: Not TGA approved. POLO trial..

Changed Olaparib + Bevacizumab in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 : 2

Alterations changed: Oncogenic mutations, Oncogenic mutations (germline). Comments changed: Combination not TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX.Not TGA approved; FDA Approved PAOLA-1; Platinum-sensitivity not yet listed as marker.

Changed Veliparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 : 2

Alterations changed: Oncogenic mutations, Oncogenic mutations (germline).

Changed Rucaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 : 2

Alterations changed: Oncogenic mutations, Oncogenic mutations (germline), M1R, M1I, V159M, V211L, V211I, R2336P, R2336H.

Changed Cemiplimab in Non-Small Cell Lung Cancer with CD274 Protein expression: 2

References changed: 33581821, 10.1016/j.annonc.2020.08.2285.

Changed Neratinib in Breast Cancer with ERBB2 Amplification

Tier changed: 21B. Comments changed: TGA approved for adjuvant therapy only. Not PBS reimbursed..

Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : 2

Alterations changed: Fusions, FGFR2-ACLY fusion, FGFR2-AFF4 fusion, FGFR2-AHCYL1 fusion, FGFR2-ARHGAP22 fusion, FGFR2-ARHGAP24 fusion, FGFR2-ATAD2 fusion, FGFR2-ATF2 fusion, FGFR2-BICC1 fusion, FGFR2-BICD1 fusion, FGFR2-CCDC158 fusion, FGFR2-CCDC170 fusion, FGFR2-CCDC6 fusion, FGFR2-CEP128 fusion, FGFR2-COL16A1 fusion, FGFR2-CTNNA3 fusion, FGFR2-DBP fusion, FGFR2-DNAJC12 fusion, FGFR2-EEA1 fusion, FGFR2-EIF4ENIF1 fusion, FGFR2-FILIP1 fusion, FGFR2-GAB2 fusion, FGFR2-GOPC fusion, FGFR2-INSC fusion, FGFR2-KCTD1 fusion, FGFR2-KIAA1217 fusion, FGFR2-KIAA1598 fusion, FGFR2-LAMC1 fusion, FGFR2-MACF1 fusion, FGFR2-MATR3 fusion, FGFR2-MCU fusion, FGFR2-NEDD4L fusion, FGFR2-NOL4 fusion, FGFR2-NRAP fusion, FGFR2-NRBF2 fusion, FGFR2-PAH fusion, FGFR2-PAWR fusion, FGFR2-POC1B fusion, FGFR2-PXN fusion, FGFR2-RABGAP1L fusion, FGFR2-RASSF4 fusion, FGFR2-RPAP3 fusion, FGFR2-SFI1 fusion, FGFR2-SHROOM3 fusion, FGFR2-SLMAP fusion, FGFR2-SOGA1 fusion, FGFR2-SPICE1 fusion, FGFR2-STRN4 fusion, FGFR2-TACC1 fusion, FGFR2-TFEC fusion, FGFR2-TRIM8 fusion, FGFR2-TTC28 fusion, FGFR2-TXLNB fusion, FGFR2-USH2A fusion, FGFR2-VCL fusion, FGFR2-WAC fusion, FGFR2-WDHD1 fusion, FGFR2-ZMYM4 fusion.

Changed Niraparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with Homologous Recombination Deficiency Score High: 2

Comments changed: Biomarker not approved by TGA. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012: HRD was determined using myChoice HRD test with cut-off score of 42-100. Note: the HR proficient group also derives benefits from Niraparib.Not TGA approved marker, but HRP also benefits from therapy.

Changed Olaparib + Bevacizumab in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with Homologous Recombination Deficiency Score High: 2

Comments changed: Biomarker and drug combination not TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX with HRD score of 42 or higher indicated a positive test.Not TGA approved; FDA Approved PAOLA-1; Platinum-sensitivity not yet listed as marker.

Changed Rucaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with Loss-of-heterozygosity score High: 2

Comments changed: Not TGA approved. FDA approved. Companion test FoundationFocus CDxBRCA LOH (cut off 16%). ARIEL3 trial: Note a low LOH is also associated with thus the biomarker not differentiating treatment benefit.Not TGA approved. ARIEL3. F1M score. Note a low LOH is also associated with benefit thus not differentiating..

Changed Crizotinib in Non-Small Cell Lung Cancer with MET Amplification, D1010, Exon 14 Deletion, Exon 14 splicing mutation, Y1003: 2

Comments changed: Not TGA or FDA approved; NCCN Category 2A. Note: no conclusive data from large trials to date.Not TGA or FDA approved; NCCN Category 2A. NB No conclusive data from large trials to date..

Changed Selpercatinib in Non-Small Cell Lung Cancer with RET : 2

Alterations changed: Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion. Comments changed: Not TGA approved. LIBRETTO-001: First-line treatment. ORR 85%Not TGA approved. LIBRETTO-001. 1L ORR 85%. References changed: 32846060, 10.1200/JCO.2020.38.15_suppl.358432846061, 10.1200/JCO.2020.38.15_suppl.3584.

Changed Selpercatinib in Thyroid Cancer with RET Fusions, CCDC6-RET fusion, NCOA4-RET fusion, CCDC186-RET fusion, ERC1-RET fusion, KTN1-RET fusion, RUFY3-RET fusion: 2

References changed: 32846061, 10.1200/JCO.2018.36.15_suppl.102, 10.1200/JCO.2019.37.15_suppl.1004532846060, 10.1200/JCO.2018.36.15_suppl.102, 10.1200/JCO.2019.37.15_suppl.10045.

Changed Selpercatinib in Medullary Thyroid Cancer with RET : 2

Alterations changed: Oncogenic mutations and NOT Amplification, M918T, V804M, V804L, C609, C611, C618, C620, C630, C634, D631_L633delinsE, E632_L633del, A883F, D631_L633delinsV, L790F, D898_E901del, D903_S904delinsEP, K666N T636_V637insCRT, D378_G385delinsEOncogenic mutations and NOT Amplification, Fusions, M918T, V804M, V804L, C609, C611, C618, C620, C630, C634, D631_L633delinsE, E632_L633del, A883F, D631_L633delinsV, L790F, D898_E901del, D903_S904delinsEP, K666N T636_V637insCRT, D378_G385delinsE.

Changed Lorlatinib in Non-Small Cell Lung Cancer with ROS1 Fusions: 2

Comments changed: Not TGA approved; Not FDA approved; NCCN 2A recommendation as subsequent-line therapy. NCT03052608: ORR 50% (6 / 12). NCT01970865: Phase 1/2- ORR 62% (TKI-naive) and 35% (prior treatment with crizotinib) with good intracranial activities.TGA approved; Not PBS Reimbursed. References changed: 29074098, 31669155.

Changed Tazemetostat in Epithelioid sarcoma with SMARCB1 Loss of protein expression, deletion: 2

Comments changed: Not TGA approved. Phase 2 but FDA approved. NCT02601950Not TGA approved. T3 but FDA approved. NCT02601950.

Changed Pembrolizumab in Cervical cancer, Endometrial cancer, Neuroendocrine tumour, Salivary gland carcinoma, Small-cell lung cancer, Thyroid cancer, Vulvar cancer with Tumour Mutational Burden High: 2

Comments changed: Not TGA approved. KEYNOTE-158. The following cancer types have higher ORR in TMB-H cohort (vs non-TMB-H). TMB cut-off at 10mut/MB..

Wednesday, 3 March 2021 (Version: 20210303AU)

New Pembrolizumab, Atezolizumab, Nivolumab + Ipilimumab, Durvalumab + Tremelimumab in Prostate cancer with CDK12 Oncogenic mutation: 4

Retrospective study identified 19 patient received immune checkpoint inhibitor. PSA50 responses 11% with estimated 9-month PFS of 23%. PFS was higher in chemotherapy-naive population. References: 32671317

New Vismodegib in Medulloblastoma with SMO D473, E518: R2

References: 21123452

New Vismodegib in Basal Cell Carcinoma with SUFU Loss-of-function mutation: R2

Xenografts models of Sufu tumors showed resistance to SMO inhibition. References: 25759019

Removed BET inhibitor in Solid tumours with BRD4 alterations Oncogenic mutations: Tier 4

Changed Trastuzumab + Paclitaxel in Breast Cancer with ERBB2 Amplification: 1

Comments changed: PBS reimbursed if ISH positive. (HER2-positivity was defined as IHC 3+ or FISH amplified. CALGB 9840).

Changed Trastuzumab + Pertuzumab + Docetaxel in Breast Cancer with ERBB2 Amplification: 1

Comments changed: PBS reimbursed if ISH positive. CLEOPATRA trial: frst-line metastastic disease OS 56.5 (vs 40.8 mo without Pertuzumab)..

Changed Trastuzumab + Cisplatin + Fluorouracil, Trastuzumab + Cisplatin + Capecitabine in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification: 1

Comments changed: PBS reimbursed if ISH positive. ToGA trial: First-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer. OS: 13.8 vs 11.1 months. (HER2 positivity: IHC 3+ or FISH: HER2:CEP17 ratio ≥2 in the tral).

Changed Abemaciclib + Letrozole, Abemaciclib + Anastrazole in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: PBS reimbursed. MONARCH-3: abemaciclib yielded significantly longer PFS in HR-positive, HER2-negative metastatic breast cancer..

Changed Palbociclib + Letrozole in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: PBS reimbursed. PALOMA-2: palbociclib yielded significantly longer PFS in HR-positive, HER2-negative metastatic breast cancer..

Changed Ribociclib + Letrozole in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 1

Comments changed: PBS reimbursed. MONALEESA-2: ribociclib yielded significantly longer PFS in HR-positive, HER2-negative metastatic breast cancer..

Changed Imatinib, Sunitinib, Regorafenib in Gastrointestinal Stromal Tumour with KIT Protein expression: 1

Comments changed: PBS reimbursed based on CD117 (c-KIT) IHC. NCCN Category 1PBS reimbursed based on CD117 IHC. NCCN Category 1.

Changed Cetuximab, Panitumumab, Cetuximab + Irinotecan in Colorectal Cancer with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Comments changed: PBS reimbursed for RAS-wild-type metastatic colorectal cancersPBS reimbursed..

Changed Temozolomide in Glioblastoma with MGMT Promoter methylation: 1

Comments changed: Standard of care. NCCN Category 1. Note MGMT status does not.

Changed Octreotide in Pancreatic neuroendocrine tumour, neuroendocrine tumour with SSTR2 Protein expression: 1

Comments changed: PBS reimbursed. PROMID trial. No significant OS differences between treatment arms due to cross-over.PBS reimbursed. PROMID OS negative due to cross-over.

Changed Trametinib in Melanoma with BRAF V600E, V600K

Tier changed: 1B2. Comments changed: TGA approved. PBS reimbursement must include concomitant dabrafenib. Single agent NOT recommended.Based on positive Phase 3 results. However single agent NOT recommended..

Changed Therapy with GLI1 Overexpression: R2

Therapy changed: VismodegibSMO inhibitor. Cancer type(s) changed: Basal Cell CarcinomaSolid tumours

Changed Therapy with GLI2 Overexpression: R2

Therapy changed: VismodegibSMO inhibitor. Cancer type(s) changed: Basal Cell CarcinomaSolid tumours

Wednesday, 24 February 2021 (Version: 20210224AU)

New Cemiplimab in Non-Small Cell Lung Cancer with CD274 Protein expression: 2

Not TGA approved. FDA Approved. EMPOWER-Lung 1: As first-line treatment, cemiplimab resulted in median PFS of 8.2 (vs 5.7 mo chemotherapy, HR 0.54) in patients with PD-L1 expression (Tumour proportion score) >= 50% as determined by the 22C3 PharmDx assay. Duration and depth of response correlate to PD-L1 TPS. References: 33581821

Removed Olaparib in Ovarian Cancer; Peritoneal Serous Carcinoma; Fallopian Tube Carcinoma with BRCA1 alterations Oncogenic mutations (germline): Tier 1B

Removed Olaparib in Ovarian Cancer; Peritoneal Serous Carcinoma; Fallopian Tube Carcinoma with BRCA2 alterations Oncogenic mutations (germline): Tier 1B

Removed Pembrolizumab in Non-small cell lung cancer with CD274+EGFR+ALK alterations CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion: Tier 1B

Changed Lorlatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: PBS reimbursed after progression on ALK inhibitor other than Crizotinib. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. In Phase 3 trial vs crizotinib (CROWN): OS was superior at12 months 78% vs 39%PBS reimbursed after progression on ALK inhibitor other than Crizotinib. In Phase 3 trial vs crizotinib (CROWN): OS was superior at12 months 78% vs 39%.

Changed Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 : 1

Alterations changed: Oncogenic mutations (germline). Comments changed: PBS reimbursed. Requires identification of class 4 or 5 mutation (germline and somatic). SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%)PBS reimbursed. Requires identification of class 4 or 5 mutation. SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%).

Changed Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 : 1

Alterations changed: Oncogenic mutations (germline). Comments changed: PBS reimbursed. Requires identification of class 4 or 5 mutation (germline and somatic). SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%)PBS reimbursed. Requires identification of class 4 or 5 mutation. SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%).

Changed Afatinib in Non-Small Cell Lung Cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 1

Comments changed: PBS reimbursed, In the first-line setting, median PFS was 11.0 vs 5.6 months for chemotherapy (LUX-Lung 6, Asian patients), 11.1 vs 6.9 months (chemotherapy, LUX-Lung 3) and afatinib has significant TTF and PFS improvement over gefitinib. LUX-Lung 7). ORR was 61% in the second-line setting (LUX-Lung 2).PBS reimbursed, LUX-Lung 6, LUX-Lung 7. References changed: 22452895, 23816960, 24439929, 27083334.

Changed Osimertinib in Non-Small Cell Lung Cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 1

Comments changed: PBS reimbursed, FLAURA: osimertinib had median DOR 17.2 months versus standard EGFR TKIs of 8.5 months.PBS reimbursed, AURA3. References changed: 27959700, 29151359.

Changed Osimertinib in Non-Small Cell Lung Cancer with EGFR : 1

Alterations changed: Exon 19 deletion, L858R, Exon 21 mutation, T790M. Comments changed: PBS reimbursed. AURA3: In second-line setting, osimertinib was found to have significantly longer PFS 10.1 vs platinum chemotherapy 4.4 months..

Changed Ado-Trastuzumab Emtansine in Breast Cancer with ERBB2 Amplification: 1

Comments changed: PBS reimbursed if ISH positive. EMILIA (T-DM1 versus lapatinib + capecitabine) and TH3RESA trials (T-DM1 versus physicians choice). HER2-positivity was defined as IHC 3+ or FISH with amplification ratio ≥2.0.PBS reimbursed if ISH positive. EMILIA and TH3RESA trials.

Changed Lapatinib + Capecitabine in Breast Cancer with ERBB2 Amplification: 1

Comments changed: PBS reimbursed if ISH positive. HER2-positivity was defined as IHC 3+ or IHC 2+ with FISH amplified in NCT00078572..

Changed Trastuzumab in Breast Cancer with ERBB2 Amplification: 1

Comments changed: PBS reimbursed if ISH positive. (HER2-positivity was defined as IHC 3+ or FISH amplifed PMID:15800309)..

Changed Trastuzumab + Capecitabine in Breast Cancer with ERBB2 Amplification: 1

Comments changed: PBS reimbursed if ISH positive. (HER2-positivity was defined as IHC 3+ or IHC 2+ with FISH amplified PMID:17679724).

Changed Anastrozole in Breast cancer with ESR1 Protein expression: 1

Comments changed: Restricted benefit: HR-positive metastatic breast cancer.Restricted benefit. HR-positive MBC.

Changed Exemestane in Breast cancer with ESR1 Protein expression: 1

Comments changed: Restricted benefit: HR-positive metastatic breast cancer.Restricted benefit. HR-positive MBC.

Changed Letrozole in Breast cancer with ESR1 Protein expression: 1

Comments changed: Restricted benefit: HR-positive metastatic breast cancer.Standard of care. Restricted benefit. HR-positive MBC.

Changed Imatinib, Sunitinib, Regorafenib in Gastrointestinal Stromal Tumour with KIT Protein expression: 1

Comments changed: PBS reimbursed based on CD117 IHC. NCCN Category 1TGA approved. PBS reimbursed based on IHC. NCCN 1.

Changed Cetuximab, Panitumumab, Cetuximab + Irinotecan in Colorectal Cancer with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1

Comments changed: PBS reimbursed..

Changed Crizotinib in Non-Small Cell Lung Cancer with ROS1 Fusions: 1

Comments changed: PBS reimbursed. ROS1-positivity is defined as gene rearrangement >15% positive cells by FISHPBS reimbursed. Gene rearrangement >15% positive cells by FISH.

Changed Entrectinib in Non-Small Cell Lung Cancer with ROS1 Fusions: 1

Comments changed: PBS reimbursed. ROS1-positivity is defined as gene rearrangement >15% positive cells by FISHTGA approved; Not PBS Reimbursed.

Changed Binimetinib + Encorafenib in Melanoma with BRAF V600E, V600K: 1B

Comments changed: Encorafenib is not PBS reimbursed. COLOMBUS trial.COLOMBUS trial. Encorafenib not PBS reimbursed..

Changed Therapy in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 Oncogenic mutations: 1B

Therapy changed: Olaparib + Bevacizumab. Comments changed: TGA approved; FDA approved. PAOLA-1.

Changed Therapy in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 Oncogenic mutations: 1B

Therapy changed: Olaparib + Bevacizumab. Comments changed: TGA approved; FDA approved. PAOLA-1.

Changed Therapy in Prostate cancer with AR AR-V7, F877L, L702H: 4

Therapy changed: MivebresibABBV-075.

Changed Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with LRP1B : 4

Alterations changed: Oncogenic mutations, deletions, truncating mutations, loss-of-function mutations.

Monday, 22 February 2021 (Version: 20210222AU)

New Pembrolizumab in Non-Small Cell Lung Cancer with CD274 Protein expression: 1

PBS reimbursed. TGA approved as monotherapy for the first-line treatment of patients with NSCLC expressing PD-L1. Defined as tumour proportion score (TPS) greater than or equal to 1%. KEYNOTE 042 and KEYNOTE-024. References: 27718847, 30955977

New Pembrolizumab in Non-Small Cell Lung Cancer with CD274 Protein expression: 1

PBS reimbursed. TGA approved as monotherapy for the subsequent-line treatment of patients with NSCLC expressing PD-L1 (defined as tumour proportion score (TPS) greater than or equal to 1%). KEYNOTE-010. References: 26712084

Changed Venetoclax in Chronic lymphocytic leukaemia with BCL2 Overexpression: 1

Comments changed: TGA approved for R/R CLL with Chr 17p deletion or for whom there are no other suitable treatment options..

Changed Dabrafenib + Trametinib in Melanoma with BRAF V600E, V600K: 1

Comments changed: PBS reimbursed. COMBI-D – Addition of trametinib to dabrafenib prolonged median PFS at 3 years (44 vs 32%)..

Changed Vemurafenib + Cobimetinib in Melanoma with BRAF V600E, V600K: 1

Comments changed: PBS reimbursed. CoBRIM – Addition of cobimetinib to vemurafenib prolonged median PFS 9.9 vs 6.2 months..

Changed Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 Oncogenic mutations (germline): 1

Comments changed: PBS reimbursed. Requires identification of class 4 or 5 mutation. SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%)PBS reimbursed, maintenance therapy.

Changed Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 Oncogenic mutations (germline): 1

Comments changed: PBS reimbursed. Requires identification of class 4 or 5 mutation. SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%)PBS reimbursed, maintenance therapy.

Changed Pembrolizumab in Urothelial carcinoma with CD274 Protein expression: 1

Comments changed: PBS reimbursed. TGA approved for cisplatin-ineligible patients with tumours express PD-L1. In KEYNOTE-052, positive PD-L1 IHC was determined by with Combined Positive Score (22C3 pharmDx assay). Overall ORR was 24% (38% in CPS >= 10%).. References changed: 26712084, 28967485.

Changed Fulvestrant + Alpelisib in Breast Cancer with PIK3CA : 1B

Alterations changed: Oncogenic mutations, C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y. Comments changed: TGA approved. Not PBS reimbursed. SOLAR-1 trial..

Friday, 19 February 2021 (Version: 20210219AU)

New Entrectinib in Medulloblastoma with NTRK3 Protein expression: 4

In vitro and in vivo DSRCT models with NTRK3 expression. Entrectinib reduces growth of cells. References: 33229458

Changed Dasatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 BCR-ABL1 Fusion: 1

Comments changed: PBS reimbursed. Second or third-line agent. Requires presence of the BCR-ABL transcript in either peripheral blood or bone marrow.PBS reimbursed. Second line treatment.

Changed Imatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 BCR-ABL1 Fusion: 1

Comments changed: PBS reimbursed. First-line treatment. Requires presence of the BCR-ABL transcript.PBS reimbursed. First line treatment.

Changed Nilotinib in Chronic Myelogenous Leukaemia with ABL1 BCR-ABL1 Fusion: 1

Comments changed: PBS reimbursed. Second or third-line agent. Requires cytogenetic evidence of the Philadelphia chromosome, or RT-PCR level of BCR-ABL transcript greater than 0.1%PBS reimbursed. Third line treatment.

Changed Ponatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 : 1

Alterations changed: BCR-ABL1 Fusion and T315IBCR-ABL1 Fusion, T315A, T315I. Comments changed: PBS reimbursed for acquired T315I mutation. Fourth line treatment. Requires cytogenetic evidence of the Philadelphia chromosome, or RT-PCR level of BCR-ABL transcript greater than 0.1%. PACE2PBS reimbursed for acquired T315I mutation. Fourth line treatment. PACE2.

Changed Alectinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: PBS reimbursed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. In first-line setting, alectinib had a superior 12 months EFS of 68% vs crizotinib 49% (ALEX trial). In J-ALEX trial, the median PFS was NR (alectinib) vs 10.2 months (crizotinib).PBS reimbursed if FISH positive.

Changed Ceritinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: PBS reimbursed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. ASCEND-5 – In post-crizotinib and chemotherapy setting, Ceritinib had superior median PFS than 5.4 v docetaxel 1.6 months. ASCEND-4 – In first-line setting, Ceritinib has superior PFS 16.6 vs platinum chemotherapy 8.1 months.PBS reimbursed if FISH positive. References changed: 24670165, 28126333, 28602779.

Changed Crizotinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: PBS reimbursed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. PROFILE1014 trial – in the first-line setting, Crizotinib had a superior PFS 10.9 vs chemotherapy 7.0 months. In the second-line setting, Crizotinib had longer PFS 7.7 vs docetaxel 3.0 months. No OS difference shown in either trials due to crossover of subgroups.PBS reimbursed if FISH positive. References changed: 20979469, 25470694.

Changed Lorlatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: PBS reimbursed after progression on ALK inhibitor other than Crizotinib. In Phase 3 trial vs crizotinib (CROWN): OS was superior at12 months 78% vs 39%PBS reimbursed. Ph3 CROWN vs crizotinib: OS 12 months 78% vs 39%.

Changed Dabrafenib in Melanoma with BRAF V600E: 1

Comments changed: PBS reimbursed. However, single-agent not recommended. Median PFS 5.1 months (NCT01227889) vs dacarbazine 2.7 months. Rate of cutaneous SCC 6%..

Changed Vemurafenib in Melanoma with BRAF V600E: 1

Comments changed: PBS reimbursed. However, single-agent not recommended. BRIM-3 – higher response rate 48% v dacarbazine 5% with superior OS (HR 0.37). Cutaneous SCC 12%..

Changed Dasatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 E255K, E255V, F359C, F359I, F359V, Y253H, A337V, P465S: 2

Comments changed: Requires presence of the BCR-ABL fusion transcript by PCR in either peripheral blood or bone marrow., and not TGA approved by biomarker. OncoKB LOE 1.BCR-ABL1 fusion required, and not TGA approved by biomarker. OncoKB LOE 1.

Changed Fulvestrant + Palbociclib + Erdafitinib in Breast Cancer with FGFR1 Amplification: 4

Comments changed: PDX study. Adding erdafitinib to palbociclib and fulvestrant induced complete responses FGFR1-amplified/ER+.

Changed Therapy in Breast Cancer with FGFR1 Amplification: R2

Therapy changed: Fulvestrant + Palbociclib, Fulvestrant + Ribociclib. References changed: 31371343, 3091463531371343,30914635.

Thursday, 18 February 2021 (Version: 20210218AU)

Tuesday, 16 February 2021 (Version: 20210216AU)

Changed Enfortumab Vedotin in Urothelial carcinoma with NECTIN4 Protein expression: 2

Comments changed: Not TGA approved. FDA accelerated approval. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells.. References changed: 31356140, 33577729.

Changed Everolimus in Subependymal giant cell astrocytoma with TSC1 : 2

Alterations changed: Oncogenic mutations (germline).

Changed Everolimus in Subependymal giant cell astrocytoma with TSC2 : 2

Alterations changed: Oncogenic mutations (germline).

Changed SHP099 + Trametinib, SHP099 + Ulixertinib in Neuroblastoma with NRAS Q61K: 4

Comments changed: Cell line study showed that NB cell line is sensitive to SHP2 inhibition (NRAS WT) but resistant to in vivo model with NRAS Q61K. Combining SHP2i with MEKi or ERKi reversed the resistance..

Changed SHP099, II-B08, RMC-4550 in Neuroblastoma with NRAS Q61K: R2

Comments changed: Cell line study showed that NB cell line is sensitive to SHP2 inhibition (NRAS WT) but resistant to in vivo model with NRAS Q61K. Combining SHP2i with MEKi or ERKi reversed the resistance..

Saturday, 13 February 2021 (Version: 20210213AU)

New Poziotinib in Non-Small Cell Lung Cancer with ERBB2 Exon 20 insertion: 3

ZENITH20. ORR 35% (combined EGFR and ERBB2 groups). PFS 5.5 months. References: 10.1016/j.annonc.2020.08.2293

New Patritumab Deruxtecan in Non-Small Cell Lung Cancer with EGFR Oncogenic mutation: 4

Treatment-refractory EGFR mutant NSCLC. ORR 25% seen in multiple mechanisms of EGFR TKI resistance. References: 10.1016/j.annonc.2020.08.2295

New Patritumab Deruxtecan in Solid tumours with ERBB3 Protein expression, Overexpression: 4

Preclinical drug development study. U3-1402 demonstrated dose-dependent and HER3-dependent antitumor activity in PDX tumors with HER3 expression. References: 31471314

Changed Lenvatinib + Pembrolizumab in Endometrial Carcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: 1B

Comments changed: TGA/FDA provisional approval. KEYNOTE-146. ORR 38% of 94 patients, including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS).. References changed: 30922731, 32167863.

Changed Pembrolizumab in Solid tumours with Mismatch repair Deficient: 1B

Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approved. ORR 34%. Median PFS 4.1months. Median OS 23.5 months..

Changed Poziotinib in Non-Small Cell Lung Cancer with EGFR Exon 20 insertion: 3

Comments changed: ZENITH20. ORR 35% (combined EGFR and ERBB2 groups). PFS 5.5 monthsZENITH20. ORR point not met but overall tumor reduction seen. AACR:2020 CT081. References changed: 10.1016/j.annonc.2020.08.2293NCT03318939.

Changed Therapy in Glioma, Glioblastoma with EGFR vIII: 4

Therapy changed: AMG-596, anti-EGFRvIII/CD3_BiTE_antibody.

Thursday, 11 February 2021 (Version: 20210211AU)

Wednesday, 10 February 2021 (Version: 20210210AU)

New SHP099, RMC-4550 in Lung adenocarcinoma with BRAF G466V, class III mutations: 4

Cell line model for Class III mutations showed relative sensitivity to SHP2 inhibitors. References: 31533235

New SHP099, RMC-4550 in Triple-negative breast cancer with BRAF G464V, class II mutations: R2

Cell line model for Class II mutation showed relative resistance to SHP2 inhibitors. References: 31533235

New Vemurafenib in Melanoma with BRAF L505H: R2

Case report. Secondary mutation acquired following Vemurafenib. References: 25515853

New BGB3245 in Glioma with BRAF V600E and L514V: R2

Type II AC-IN/DFG-OUT RAF dimer inhibitor BGB3245. References: 29880583

New Vemurafenib, Dabrafenib, PLX8394 in Glioma with BRAF V600E and L514V: R2

Secondary mutation acquired following dabrafenib, inducing BRAF Dimerization. References: 29880583

Changed Dabrafenib + Trametinib with BRAF V600E: 4

Cancer type(s) changed: Pancreatic AdenocarcinomaPancreatic adenocaricnoma

Monday, 8 February 2021 (Version: 20210208AU)

New Ivosidenib + Azacitidine in Acute Myeloid Leukaemia with IDH1 Oncogenic mutations: 3

N=23. ORR 78%. CR 61%. OS at 12 months 82%. References: 33119479

New Ipatasertib in Solid tumours with AKT3 Oncogenic mutations, E17K, L51R, Q78K: 4

No clinical data on using a pan-AKT inhibitor for AKT2/3 gain of function mutations, but clinical activities of these mutations are being examined in Phase 2 trials. References: NCT04589845

New Trametinib in Histiocytosis with BRAF N486_P490del: 4

Two case reports. Langerhans cell histiocytosis responders to Trametinib (1PR, 1 durable CR). References: 32991018

New Dabrafenib + Trametinib in Pancreatic adenocaricnoma with BRAF V600E: 4

Case report. Sustained response reported. References: 10.1200/JCO.2018.36.4_suppl.214

New Trametinib in Histiocytosis with MAP2K1 K57_G61del: 4

Case report. Langerhans cell histiocytosis responder to Trametinib. References: 32991018

Changed Binimetinib + Encorafenib + Cetuximab in Colorectal Cancer with BRAF V600E: 2

Comments changed: Not TGA approved. Triplet OS 9.3 months. Doublet recommended.Not TGA approved. Doublet recommended. References changed: 31566309, 33503393.

Changed Encorafenib + Cetuximab in Colorectal Cancer with BRAF V600E: 2

Comments changed: Not TGA approved. FDA approved. OS for E+C doublet 9.3 months. ORR 26.8%.. References changed: 31566309, 33503393.

Changed Ipatasertib in Solid tumours: 4

Biomarker changed: AKT1AKT2. Alterations changed: Oncogenic mutations, L52R, Q79K.

Changed Ipatasertib in Solid tumours: 4

Biomarker changed: AKT2AKT3. Alterations changed: Oncogenic mutations, E17K.

Changed Telisotuzumab Vedotin in Lung Squamous Cell Carcinoma with MET Overexpression: R2

References changed: 33125909, 33221175, 10.1200/JCO.2019.37.15_suppl.907533125909, 10.1200/JCO.2019.37.15_suppl.9075.

Wednesday, 3 February 2021 (Version: 20210203AU)

New Elacestrant in Breast cancer with ESR1 Protein expression: 3

Phase I. N=50 with ORR 19%. 52% treated with prior SERD. References: 33513026

New Mirdametinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

NF106. Phase II trial. ORR 42%; CBR 95%. References: 33507822

New Elacestrant in Breast cancer with ESR1 Y537S, D538G, Y537N, E380Q, L536H, L536P: 4

Objective responses seen in 5 of 15 (33%) patients. References: 33513026

Tuesday, 2 February 2021 (Version: 20210202AU)

New Eprenetapopt + Azacitidine in Myelodysplastic syndrome, Acute myeloid leukaemia with TP53 Oncogenic mutation: 3

Ph I/II study. N=55 ORR 71%; CR 44%. References: 33449813

New Rogaratinib in Urothelial Carcinoma with FGFR1 Overexpression: 4

Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation). References: 31405822

New Rogaratinib in Urothelial Carcinoma with FGFR2 Overexpression: 4

Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation). References: 31405822

New Rogaratinib in Urothelial Carcinoma with FGFR3 Overexpression: 4

Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation). References: 31405822

New Selpercatinib, Pralsetinib in Medullary Thyroid Cancer with RET Y806C, Y806N, G810C, G810S, V738A: R2

Case report. Acquired resistance after treatment with Selpercatinib habouring KIF5B-RET fusion detected by cfDNA. Cell line cross-profiling of additional resistant mutations. References: 33161056

Sunday, 24 January 2021 (Version: 20210124AU)

Friday, 22 January 2021 (Version: 20210122AU)

Removed Ponatinib in Acute Lymphoblastic Leukaemia with ABL1 alterations BCR-ABL1 Fusion: Tier 2

Changed Ponatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 BCR-ABL1 Fusion, T315A, T315I: 1

Comments changed: PBS reimbursed for acquired T315I mutation. Fourth line treatment. PACE2.

Changed Dasatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 E255K, E255V, F359C, F359I, F359V, Y253H, A337V, P465S: 2

Comments changed: BCR-ABL1 fusion required, and not TGA approved by biomarker. OncoKB LOE 1Not TGA approved by mutation; FDA approved; OncoKB LOE 1.

Changed Bosutinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 E255K, E255V,F317C, F317I, F317L, F317V, F359C, F359I, F359V, T315A, Y253H, A337V, P465S: 2

Comments changed: BCR-ABL1 fusion required, and not TGA approved by biomarker. OncoKB LOE 1Not TGA approved by mutation; FDA approved; OncoKB LOE 1.

Changed Nilotinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 F317C, F317I, F317L, F317V, T315A, V299L, A337V, P465S: 2

Comments changed: BCR-ABL1 fusion required, and not TGA approved by biomarker. OncoKB LOE 1Not TGA approved by mutation; FDA approved; OncoKB LOE 1.

Changed Imatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 V299L, A337V, P465S: 2

Comments changed: BCR-ABL1 fusion required, and not TGA approved by biomarker. Adapted from APAR..

Changed Ponatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 Y253H, E255K, E255V, V299L, F317L, F317C, F317I, F317V, F359C, F359V, F359I, A337V, P465S: 2

Comments changed: BCR-ABL1 fusion required, and not TGA approved by biomarker. Adapted from APAR.Not TGA approved; Adapted from APAR.

Thursday, 21 January 2021 (Version: 20210121AU)

New Olaparib in Solid tumours with SLX4 Loss-of-function mutation: 4

Cell line study showing differential sensitivity to olaparib in SLX4 mutants (vs. wild type). References: 27084631

Wednesday, 20 January 2021 (Version: 20210120AU)

New Ipatasertib in Solid tumours with AKT2 Oncogenic mutations: 4

No clinical data on using a pan-AKT inhibitor for AKT2/3 gain of function mutations, but clinical activities of these mutations are being examined in Phase 2 trials. References: NCT04589845

New Ipatasertib in Solid tumours with AKT3 Oncogenic mutations: 4

No clinical data on using a pan-AKT inhibitor for AKT2/3 gain of function mutations, but clinical activities of these mutations are being examined in Phase 2 trials. References: NCT04589845

New Olaparib in Prostate cancer with FANCG Oncogenic mutations: 4

FANCG mutation listed in TOPARP-B inclusion criteria. 1 case recruited only (castrate sensitive disease). References: 31806540

New Entrectinib, Brigatinib, Repotrectinib in Solid tumours with ROS1 Amplification: 4

STARTRK-1 reported only 1 case of amplification. ROS1 amplification included as inclusion criteria for NCT02097810, NCT03868423, NCT04094610. References: 28183697, NCT02097810, NCT03868423, NCT04094610

Changed Afatinib in Urothelial Carcinoma with ERBB3 G284R, V104M, R103G: 4

References changed: 27044931, 25953157.

Saturday, 16 January 2021 (Version: 20210116AU)

Changed Fam-trastuzumab deruxtecan-nxki in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. DESTINY-Gastric01, No response if ISH+ and HER2 2+.

Thursday, 14 January 2021 (Version: 20210114AU)

New Capivasertib in Solid tumours with AKT1 E17K: 3

Phase 2 study. NCI-MATCH Subprotocol EAY131-Y. Confirmed ORR 28% with 1 CR. 6-month PFS: 50%. Subtypes that has demonstrated response: luminal breast cancers, uterine leiomyosarcoma, parotid gland carcinoma, and adenocarcinoma of cervix. References: 33377972

Wednesday, 13 January 2021 (Version: 20210113AU)

New Tazemetostat in Ovarian Small Cell Carcinoma with SMARCA4 Loss-of-function mutation: 4

Single case report of SCCOHT. Concurrent loss of SMARCA2 expression. Partial response after four months with clinical benefit of eight months seen in chemo-resistant disease. References: 32575483

Changed Tazemetostat in Ovarian Small Cell Carcinoma with SMARCA2 Loss-of-function mutation: 4

Comments changed: Xenograft and cell line SCCOHT models. Induces potent antiproliferative and antitumour effects..

Changed Tazemetostat in Ovarian Small Cell Carcinoma with SMARCA4 Loss-of-function mutation: 4

Comments changed: Xenograft and cell line SCCOHT models. Induces potent antiproliferative and antitumour effects..

Tuesday, 12 January 2021 (Version: 20210112AU)

New Trametinib in Melanoma with RAF1 Fusion; ANO10-RAF1 fusion: 4

Case report. Significant disease response. Duration of response < 6 months. References: 10.1200/PO.17.00138

New Cobimetinib in Anaplastic Pleomorphic Xanthoastrocytoma with RAF1 Fusion; ATG7-RAF1 fusion: 4

Case report. Sustained response with complete cytologic response in CSF. References: 10.1200/PO.18.00298

New Cobimetinib in Melanoma with RAF1 Fusion; GOLGA4-RAF1 fusion: 4

Case report. References: 30835257

New Trametinib in Pilocytic astrocytoma with RAF1 Fusion; NFIA-RAF1 fusion: 4

Case report. Paediatric low-grade glioma. Case report. Stable disease for 12 months. References: 27810072

New LY3009120 in Low-grade gliomas with RAF1 Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion: 4

Paediatric low-grade gliomas. References: 28806393

New Trametinib in Low-grade gliomas with RAF1 Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion: 4

Paediatric low-grade gliomas. Response in cell line model but not in xenograft. References: 28806393

New Trametinib in Pancreatic Acinar Cell Carcinoma with RAF1 Fusion; GATM-RAF1 fusion: R2

No objective response seen. Concomitant mutations reported including CDKN2A loss. References: 10.1200/PO.19.00159

New Vemurafenib, PLX8394 in Low-grade gliomas with RAF1 Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion: R2

Paediatric low-grade gliomas. References: 28806393

Changed Therapy in Solid tumours, Liquid Cancers with TP53 Oncogenic mutations: R2

Therapy changed: MDM2 inhibitor, SAR405838MDM2 inhibitor, MDMX inhibitor.

Tuesday, 5 January 2021 (Version: 20210105AU)

New Crizotinib in Non-Small Cell Lung Cancer with MET Exon 14 deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 4

Case reports. References: 26845194, 27022036

New Crizotinib, Cabozantinib in Non-Small Cell Lung Cancer with MET Exon 14 deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 4

Case series. References: 26896094

New Crizotinib in Non-Small Cell Lung Cancer with MET Y1003S: 4

Case report showing significant response and DOR. References: 30885356

New Crizotinib in Non-Small Cell Lung Cancer with MET Y1021H: 4

Case report, sensitive to Crizotinib. References: 31809977

New Crizotinib in Non-Small Cell Lung Cancer with EGFR Amplification: R2

Case series. EGFR Amplification in three cases. References: 31548343

New Crizotinib in Non-Small Cell Lung Cancer with KRAS Amplification: R2

Case series. References: 31548343

New Crizotinib in Non-Small Cell Lung Cancer with MET D1228N: R2

References: 27343442

New Crizotinib in Non-Small Cell Lung Cancer with MET D1246N: R2

Case report. Emergent variant post exposure to Crizotinib. Possible Acquired resistance. References: 31809977

New Crizotinib in Non-Small Cell Lung Cancer with MET F1007fs: R2

Case report. Primary resistance to crizotinib. References: 29935852

New Crizotinib in Non-Small Cell Lung Cancer with MET G1163R, D1228H, D1228A, Y1230H: R2

Case report. Emergent mutations detected on ctDNA at the time progression after treatment with crizotinib. References: 29110851

New Crizotinib in Non-Small Cell Lung Cancer with MET Y1230C: R2

Case report. Pre-treatment D1010H sensitizing to crizotinib. References: 27666659

New Crizotinib in Non-Small Cell Lung Cancer with MET Y1230H: R2

Case report. Acquired resistance. References: 28629543

New Crizotinib in Non-Small Cell Lung Cancer with MET Y1230S, Y1230H, D1228N, D1228H, F1200I, L1195V, S244fs: R2

Case series. References: 31548343

New Crizotinib in Non-Small Cell Lung Cancer with MET+TP53 MET:Exon 14 skipping mutation and TP53:oncogenic mutation: R2

Case series. TP53 mutation shown in post-exposure to crizotinib 7 of 12 cases. References: 31548343

New Crizotinib in Non-Small Cell Lung Cancer with NF1 Oncogenic mutation: R2

Case series. References: 31548343

Changed Crizotinib in Non-Small Cell Lung Cancer with MET Amplification, D1010, Exon 14 Deletion, Exon 14 splicing mutation, Y1003: 2

Comments changed: Not TGA or FDA approved; NCCN Category 2A. NB No conclusive data from large trials to date.Not TGA approved; FDA orphan drug indication.

Thursday, 31 December 2020 (Version: 20201231AU)

New Vemurafenib + Cobimetinib in Colorectal Cancer with BRAF V600: 3

TAPUR Phase 2 Basket trial. ORR 29%. References: 10.1200/JCO.2020.38.4_suppl.122

New Cetuximab + Irinotecan + Vemurafenib in Colorectal Cancer with BRAF V600E: 3

Phase 2 SWOG S1406. Triplet including vemurafenib (vs without) improved ORR (17 v 4%) with improved PFS (4.2 v 2.0 mo). References: 33356422

New Dabrafenib + Trametinib in Solid tumours except colorectal cancer, melanoma, thyroid cancer with BRAF V600E: 3

NCI-MATCH Trial Subprotocol H. N=23. ORR 38%. Colorectal cancer, melanoma, thyroid cancers were excluded. References: 32758030

New Tazemetostat in Follicular Lymphoma with EZH2 Y646F, Y646N, Y646S, Y646H, Y646C, A682G, A692V: 3

Single-arm study in relapsed or refractory disease. ORR 69% in EZH2 mutant group (vs 35% in wildtype). EZH2 hotspot oncogenic mutation. References: 33035457

New Nilotinib in Melanoma with KIT Exon 11 mutation, Exon 11 deletion, L576P, K642E, I817L, V559A: 3

Phase II UN10-06 trial. Exon 11 mutation ORR 29%. One responder I817L. References: 26424760

New Ivosidenib in Chondrosarcoma with IDH1 R132: 4

Phase 1 trial. Treatment with ivosidenib resulted in no objective response, but with a CBR 52% and associated reduction of 2HG level. References: 32208957

New Imatinib in Adenoid Cystic Carcinoma with KIT Overexpression: 4

Mixed results in one case series (one responder of 8), but no response in a separate Phase II consortium study (N=15). References: 16135502, 15659505

New Binimetinib in Ovarian cancer with KRAS Oncogenic mutation: 4

MILO/ENGOT-ov11. Low-grade serous ovarian cancers. Single-agent binimetinib did not improve PFS. Post-hoc KRAS mutant population ORR 44% (vs. wildtype 19%). References: 32822286

New Nilotinib in Melanoma with KIT Amplification: R2

Phase II UN10-06 trial. In KIT amplification only subgroup, only 1/15 response with with DOR of 5 weeks only (ORR 6%). Gene co-mutation status was not available in the case. References: 26424760

New Nilotinib in Melanoma with KIT Exon 13 mutation: R2

Phase II UN10-06 trial. In KIT exon 13 mutation subgroup, 0/15 response. Gene co-mutation status was not available in the case. References: 26424760

Changed Brigatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1B

References changed: 30280657, 32780660.

Changed Rucaparib in Prostate cancer with BRCA1 Oncogenic mutations: 2

References changed: 32795228, 10.1093/annonc/mdy284.002.

Changed Rucaparib in Prostate cancer with BRCA2 Oncogenic mutations: 2

References changed: 32795228, 10.1093/annonc/mdy284.002.

Changed Imatinib in Melanoma with KIT Oncogenic mutations and NOT Amplification: 3

Comments changed: ORR 54% in KIT mutationORR 54% in mutated.

Changed Imatinib in Melanoma with KIT : 3

Alterations changed: Oncogenic mutations and NOT Amplification and NOT Exon 17 mutationOncogenic mutations except Exon 17 mutation.

Changed Imatinib in Melanoma with KIT Amplification: R2

Comments changed: ORR 0% in KIT amplification only.

Monday, 21 December 2020 (Version: 20201221AU)

Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion

Tier changed: 1B2. Comments changed: Not TGA approved; FDA approved; Checkmate 227.

Saturday, 19 December 2020 (Version: 20201219AU)

Changed Pralsetinib in Medullary Thyroid Cancer with RET Oncogenic mutations and NOT Amplification: 2

Comments changed: Not TGA approved. FDA approved; ARROW..

Changed Pralsetinib in Non-Small Cell Lung Cancer with RET Fusions

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. ARROW. ORR 65%. DCR 93%Not TGA approved. ARROW. References changed: 10.1200/JCO.2019.37.15_suppl.9008; 10.1200/JCO.2020.38.15_suppl.9515.

Friday, 18 December 2020 (Version: 20201218AU)

New Margetuximab + Capecitabine, Margetuximab + Eribulin, Margetuximab + Gemcitabine, Margetuximab + Vinorelbine in Breast Cancer with ERBB2 Amplification; Overexpression: 2

FDA approval for margetuximab and chemotherapy combination. References: 10.1200/JCO.2019.37.15_suppl.1000

New Margetuximab in Solid tumours with ERBB2 Overexpression: 4

References: 28119295

Changed Rituximab in Non-Hodgkin’s Lymphoma, Chronic lymphocytic leukaemia, Acute lymphoblastic leukaemia, Hodgkin’s Lymphoma with CD20 Protein expression: 1

Comments changed: PBS reimbursed. References non-exhaustivePBS reimbursed. Reference non-exhaustive.

Changed PLX8394, RAF dimer inhibitor in Solid tumours with BRAF Fusions: 4

Comments changed: Class II mutations. Review articleClass II mutation. Review article. For trial matching.

Changed RAF dimer inhibitor in Solid tumours with BRAF K601, K601E: 4

Comments changed: Class II mutationsClass II mutation, For trial matching.

Changed immune checkpoint blockade,PD-L1 targeting in Solid tumours with CD274 Amplification: 4

Comments changed: For trial matching.

Tuesday, 15 December 2020 (Version: 20201215AU)

New Nivolumab in Solid tumours except Colorectal Cancer with MLH1 Loss of protein expression: 3

NCI-MATCH (EAY131) Z1D-A subprotocol. Defined as complete loss of MLH1/MSH2 IHC. ORR 36%. References: 31765263

New Nivolumab in Solid tumours except Colorectal Cancer with MSH2 Loss of protein expression: 3

NCI-MATCH (EAY131) Z1D-A subprotocol. Defined as complete loss of MLH1/MSH2 IHC. ORR 36%. References: 31765263

New Olaparib in Neuroblastoma with ATRX Loss-of-function mutation: 4

Cell line study. References: 32846370

New Olaparib in Prostate cancer with NBN Oncogenic mutation: 4

Hypothetical biomarker in TOPARP. Only one patient in the entire cohort. References: 31806540

New Olaparib in Prostate cancer with NBN Oncogenic mutation: 4

TRITON2. No PSA response in 4 patients. References: 32086346

Changed Lorlatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: TGA approved. PBS reimbursed. Ph3 CROWN vs crizotinib: OS 12 months 78% vs 39%.

Changed Dabrafenib in Melanoma with BRAF V600E: 1

Comments changed: PBS reimbursed. However, single-agent not recommended..

Changed Vemurafenib in Melanoma with BRAF V600E: 1

Comments changed: PBS reimbursed. However, single-agent not recommended. BRIM-3.

Changed Pembrolizumab in Solid tumours with Microsatellite Instability High

Tier changed: 1B2. Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approvedNot TGA approved for MSI-H; FDA approved.

Changed Pembrolizumab in Solid tumours with Mismatch repair Deficient

Tier changed: 1B2. Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approvedNot TGA approved for dMMR; FDA approved.

Changed Pembrolizumab in Solid tumours with MLH1 Loss of protein expression

Tier changed: 1B2. Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approvedNot TGA approved for dMMR; FDA approved.

Changed Pembrolizumab in Solid tumours with MSH2 Loss of protein expression

Tier changed: 1B2. Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approvedNot TGA approved for dMMR; FDA approved.

Changed Pembrolizumab in Solid tumours with MSH6 Loss of protein expression

Tier changed: 1B2. Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approvedNot TGA approved for dMMR; FDA approved.

Changed Pembrolizumab in Solid tumours with PMS2 Loss of protein expression

Tier changed: 1B2. Comments changed: TGA provisional approval for MSI-H/dMMR. FDA approvedNot TGA approved for MSI-H; FDA approved.

Changed Ipilimumab + Nivolumab in Colorectal Cancer with Microsatellite Instability High: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review)Not TGA approved for MSI-H. FDA approved.

Changed Nivolumab in Colorectal Cancer with Microsatellite Instability High: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142Not TGA approved for MSI-H. FDA approved. CheckMate-142.

Changed Ipilimumab + Nivolumab in Colorectal Cancer with Mismatch repair Deficient: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review)Not TGA approved for dMMR. FDA approved.

Changed Nivolumab in Colorectal Cancer with Mismatch repair Deficient: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142Not TGA approved for dMMR. FDA approved.

Changed Ipilimumab + Nivolumab in Colorectal Cancer with MLH1 Loss of protein expression: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review)Not TGA approved for dMMR; FDA approved.

Changed Nivolumab with MLH1 Loss of protein expression: 2

Cancer type(s) changed: Colorectal CancerSolid tumours Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142Not TGA approved for dMMR; FDA approved.

Changed Ipilimumab + Nivolumab in Colorectal Cancer with MSH2 Loss of protein expression: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review)Not TGA approved for dMMR; FDA approved.

Changed Nivolumab with MSH2 Loss of protein expression: 2

Cancer type(s) changed: Colorectal CancerSolid tumours Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142Not TGA approved for dMMR; FDA approved.

Changed Ipilimumab + Nivolumab in Colorectal Cancer with MSH6 Loss of protein expression: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review)Not TGA approved for dMMR; FDA approved.

Changed Nivolumab with MSH6 Loss of protein expression: 2

Cancer type(s) changed: Colorectal CancerSolid tumours Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142Not TGA approved for dMMR; FDA approved.

Changed Ipilimumab + Nivolumab in Colorectal Cancer with PMS2 Loss of protein expression: 2

Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. DCR 12 weeks 70% (central review)Not TGA approved for MSI-H; FDA approved.

Changed Nivolumab with PMS2 Loss of protein expression: 2

Cancer type(s) changed: Colorectal CancerSolid tumours Comments changed: Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142Not TGA approved for MSI-H; FDA approved. Checkmate-142.

Changed Midostaurin in Solid tumours with KIT D816V, T670A, T670V: 4

Comments changed: Cell line study. Note reduced sensitivity.

Monday, 14 December 2020 (Version: 20201214AU)

New Lenvatinib + Pembrolizumab in Endometrial Carcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: 1B

TGA/FDA provisional approval. KEYNOTE-146. ORR 38% of 94 patients, including 10 CR. References: 30922731

Removed Ponatinib in Acute Lymphoblastic Leukaemia; Chronic Myelogenous Leukaemia with ABL1 alterations T315A, T315I: Tier 1

Changed Ponatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1 : 1

Alterations changed: BCR-ABL1 Fusion, T315A, T315IBCR-ABL1 Fusion; ABL1:T315I. Comments changed: PBS reimbursed for acquired T315I mutation. Fourth line treatment.

Sunday, 13 December 2020 (Version: 20201213AU)

New Capivasertib + Paclitaxel in Triple-negative breast cancer with AKT1 E17K: 3

PAKT PFS 9.3 v 3.7 mo in PIK3CA/AKT/PTEN altered subgroup. OS/ORR NS. References: 31841354

New Olaparib + Durvalumab in Breast Cancer with BRCA1 Oncogenic mutations (germline): 3

MEDIOLA breast cancer cohort, including both TNBC and non-TNBC. Maximum of two lines of prior treatments. ORR 63%. DCR 28 weeks: 50%. Note: PD-L1 (at 1%) status NS. References: 32771088

New Olaparib + Durvalumab in Breast Cancer with BRCA2 Oncogenic mutations (germline): 3

MEDIOLA breast cancer cohort, including both TNBC and non-TNBC. Maximum of two lines of prior treatments. ORR 63%. DCR 28 weeks: 50%. Note: PD-L1 (at 1%) status NS. References: 32771088

New Nivolumab in Solid tumours except Colorectal Cancer with Mismatch repair Deficient: 3

NCI-MATCH (EAY131) Z1D-A subprotocol. Defined as complete loss of MLH1/MSH2 IHC. ORR 36%. References: 31765263

New Capivasertib + Paclitaxel in Triple-negative breast cancer with PIK3CA R88Q, N345K, C420R, E542, E545, Q546, M1043I, H1047, G1049R: 3

PAKT PFS 9.3 v 3.7 mo in PIK3CA/AKT/PTEN altered subgroup. OS/ORR NS. References: 31841354

New Capivasertib + Paclitaxel in Triple-negative breast cancer with PTEN Loss-of-function mutation: 3

PAKT PFS 9.3 v 3.7 mo in PIK3CA/AKT/PTEN altered subgroup. OS/ORR NS. References: 31841354

New Pembrolizumab in Uterine Carcinosarcoma with POLE P286R, T323A: 4

Case report. The case also had a high tumour mutational burden. References: 29386312

Saturday, 12 December 2020 (Version: 20201212AU)

New Dasatinib + Blinatumomab in Acute Lymphoblastic Leukaemia with ABL1 BCR-ABL1 Fusion: 2

GIMEMA LAL2116 D-ALBA trial. CR rate 98%. OS 18 month: 95%. DFS: 88%. References: 33085860

New Olaparib in Prostate cancer with ATM Oncogenic mutations: R2

Updated: PROFOUND trial: No overall PFS difference in , although benefits in patients previously treated with a taxane was noted (not sufficiently powered). References: 32343890, 32955174

New Pembrolizumab in Colorectal Cancer with KRAS+Microsatellite Instability KRAS:oncogenic mutation AND Microsatellite Instability:High: R2

KRAS subgroup showed no PFS benefit in KEYNOTE-177. References: 33264544

New Pembrolizumab in Colorectal Cancer with KRAS+Mismatch repair KRAS:oncogenic mutation AND Mismatch repair:deficient: R2

KRAS subgroup showed no PFS benefit in KEYNOTE-177. References: 33264544

Removed Olaparib in Prostate cancer with ATM alterations Oncogenic mutation: Tier 3

Changed Lorlatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1

Comments changed: TGA approved. PBS reimbursed. Ph3 CROWN vs crizotinib: OS 12 months 78% vs 39%. References changed: 30413378, 33207094, 10.1016/j.annonc.2020.08.228230413378, 10.1016/j.annonc.2020.08.2282.

Changed Atezolizumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion: 1B

Comments changed: TGA approved; IMPower110; 1L treatment. PD-L1 positive. Median OS: 20 vs 13 months (chemotherapy)TGA approved; FDA approved; IMPower110. References changed: 32997907, 10.1093/annonc/mdz293.

Changed Pembrolizumab in Colorectal Cancer with Microsatellite Instability High

Tier changed: 1B2. Comments changed: TGA provisionally approved for MSI-H/dMMR. KEYNOTE-177. PFS v chemotherapy: 16.5 vs. 8.2 months. Note KRAS mutant subgroup PFS NS.Not TGA approved for MSI-H. KEYNOTE-177. References changed: 33264544, 10.1200/JCO.2020.38.18_suppl.LBA4.

Changed Pembrolizumab in Colorectal Cancer with Mismatch repair Deficient

Tier changed: 1B2. Comments changed: TGA provisionally approved for MSI-H/dMMR. KEYNOTE-177. PFS v chemotherapy: 16.5 vs. 8.2 months. Note KRAS mutant subgroup PFS NS.Not TGA approved for dMMR. References changed: 33264544, 10.1200/JCO.2020.38.18_suppl.LBA4.

Changed Olaparib in Prostate cancer with BRCA1 Oncogenic mutations: 2

References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with BRCA2 Oncogenic mutations: 2

References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with BARD1 Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: 1 patient only.. References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with BRIP1 Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: 3 patients only.. References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with CHEK1 Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: 1 patient only..

Changed Olaparib in Prostate cancer with CHEK2 Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: 12 patients. HR: 0.87 not powered..

Changed Olaparib in Prostate cancer with FANCL Oncogenic mutations: 4

References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with PALB2 Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: 4 patient. Subgroup not compared.. References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with RAD51B Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: 1 patient in control arm.. References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with RAD51D Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: 1 patient only.. References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with RAD54L Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B: Subgroup not compared.. References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with ATM Oncogenic mutations: R2

Comments changed: Retrospective study. ORR 0%. No HR difference in PROFOUND trial. References changed: 30797618, 32343890.

Changed Olaparib in Prostate cancer with CDK12 Oncogenic mutation

Tier changed: R24. Comments changed: PROFOUND trial; Cohort B. PFS 5.1 v 2.2 mo NS. No OS benefit (HR 0.97) in both adjusted and unadjusted analyses.. References changed: 32343890, 32955174.

Changed Olaparib in Prostate cancer with PPP2R2A Oncogenic mutation

Tier changed: R23. Comments changed: PROFOUND trial; Cohort B. No OS benefit or cell line data to suggest PPP2R2A Is synthetically lethal with Olaparib.. References changed: 32343890, 32955174.

Friday, 11 December 2020 (Version: 20201211AU)

Removed Dabrafenib + Trametinib in Anaplastic Thyroid Cancer with BRAF alterations V600E: Tier 2

Changed Atezolizumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:oncogenic mutation and NOT ALK:fusion

Tier changed: 1B2. Comments changed: Not TGA approved; FDA approved; IMPower110.

Changed Ripretinib in Gastrointestinal Stromal Tumour with KIT

Alterations changed: Protein expression; Oncogenic mutations. Tier changed: 1B2. Comments changed: TGA approved; Not PBS ReimbursedNot TGA approved; FDA approved.

Changed Imatinib with PDGFRA FIP1L1-PDGFRA Fusion; Fusion: 1B

Cancer type(s) changed: Myelodysplastic/Myeloproliferative diseasesMyelodysplastic/Myeloproliferative Neoplasms

Changed Imatinib with PDGFRB Fusions: 1B

Cancer type(s) changed: Myelodysplastic/Myeloproliferative diseasesMyelodysplastic/Myeloproliferative Neoplasms

Changed Pembrolizumab in Cervical cancer with CD274 Protein expression

Tier changed: 21B. Comments changed: Not TGA approved. KEYNOTE-028 and 158TGA approved. Not PBS reimbursed. KEYNOTE-028 and 158.

Changed Pembrolizumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with CD274 Protein expression

Tier changed: 21B. Comments changed: Not TGA approved. FDA approvedTGA approved. Not PBS reimbursed.

Changed Pembrolizumab in Oesophageal squamous cell carcinoma with CD274 Protein expression

Tier changed: 21B.

Wednesday, 9 December 2020 (Version: 20201209AU)

Changed Ponatinib in Acute Lymphoblastic Leukaemia, Chronic Myelogenous Leukaemia with ABL1

Alterations changed: BCR-ABL1 Fusion; ABL1:T315I. Tier changed: 1B.

Changed Lorlatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed. Ph3 CROWNTGA approved. Not PBS reimbursed. Ph3 CROWN.

Changed Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA1 Oncogenic mutations (germline): 1

Comments changed: PBS reimbursed, maintenance therapyTGA approved, PBS reimbursed, maintenance.

Changed Olaparib in Ovarian Cancer, Peritoneal Serous Carcinoma, Fallopian Tube Carcinoma with BRCA2 Oncogenic mutations (germline): 1

Comments changed: PBS reimbursed, maintenance therapyTGA approved, PBS reimbursed, maintenance.

Changed Crizotinib in Non-Small Cell Lung Cancer with ROS1 Fusions: 1

Comments changed: PBS reimbursed. Gene rearrangement >15% positive cells by FISH.

Changed Entrectinib in Solid tumours with NTRK1 Fusions: 1B

Comments changed: TGA approved. Not PBS reimbursedNot TGA approved.

Changed Entrectinib in Solid tumours with NTRK2 Fusions: 1B

Comments changed: TGA approved. Not PBS reimbursedNot TGA approved.

Changed Entrectinib in Solid tumours with NTRK3 Fusions: 1B

Comments changed: TGA approved. Not PBS reimbursedNot TGA approved.

Changed Entrectinib in Non-Small Cell Lung Cancer with ROS1 Fusions

Tier changed: 1B.

Changed Lorlatinib in Non-Small Cell Lung Cancer with ROS1 Fusions

Tier changed: 21B. Comments changed: TGA approved; Not PBS ReimbursedNot TGA approved.

Changed Therapy in Malignant peripheral nerve sheath tumor with NF1+SUZ12 NF1:loss-of-function mutation AND SUZ12:loss-of-function mutation: 4

Therapy changed: Mirdametinib + JQ1MEK inhibitor + JQ1.

Changed Olaparib in Prostate cancer with CDK12 Loss-of-function mutations: R2

Comments changed: No RECIST/PSA response in TOPARP-B trial subgroup.TOPARP-B subgroup.

Tuesday, 8 December 2020 (Version: 20201208AU)

New Afatinib in Solid tumours with ERBB2 G660D and S310F, G660D, V659E, V659D: 4

Transmembrane mutation. ERBB2 TKIs, such as lapatinib, neratinib, pyrotinib, and poziotinib hypothesised to have antitumour activity. References: 29146616

Changed Olaparib in Prostate cancer with CDK12 Oncogenic mutation

Tier changed: 43. Comments changed: PROFOUND trial; Cohort B. PFS 5.1 v 2.2 mo NS..

Monday, 7 December 2020 (Version: 20201207AU)

Changed Therapy in Triple-negative Breast Cancer with CD274 Protein expression: 2

Therapy changed: Pembrolizumab + Nab-paclitaxel, Pembrolizumab + Paclitaxel, Pembrolizumab + Carboplatin + Gemcitabine.

Friday, 4 December 2020 (Version: 20201204AU)

New Gefitinib in Non-Small Cell Lung Cancer with FBXW7 Deletion: R2

References: 29633504

New Pembrolizumab in Melanoma with FBXW7 Loss-of-function mutation, R505: R2

References: 32371478

Changed Ibrutinib in Waldenstroms macroglobulinemia with MYD88 : 2

Alterations changed: Oncogenic mutations, L265P.

Changed 177Lu-PSMA radioconjugate in Prostate cancer with PSMA Protein expression: 3

Comments changed: PSARR: 66% v Cabazitaxel. Imported from POTTR. References changed: 10.1200/JCO.2020.38.15_suppl.5500, 29752180.

Changed Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody with Tumour Mutational Burden High: 3

Cancer type(s) changed: Solid tumours except Colorectal Cancer

Changed MK-2206 + Gemcitabine in Solid tumours with EGFR+ERRFI1 : 4

Alterations changed: EGFR:low expression AND ERRFI1:oncogenic mutations.

Changed Gefitinib + Gemcitabine in Solid tumours with EGFR+ERRFI1 : 4

Alterations changed: EGFR:overexpression AND ERRFI1:oncogenic mutations.

Tuesday, 1 December 2020 (Version: 20201201AU)

New Nivolumab + Ipilimumab in Non-Small Cell Lung Cancer with Tumour Mutational Burden High: 2

Not TGA approved. Phase 3 CHECKMATE 227. Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort. Median PFS: 7.2 vs 5.5 months. Not correlated with TMB. References: 29658845

New Nivolumab in Non-Small Cell Lung Cancer with Tumour Mutational Burden High: 4

Exploratory analysis from Checkmate 026. References: 28636851

Monday, 30 November 2020 (Version: 20201130AU)

Changed Rucaparib in Prostate cancer with BRCA1 Oncogenic mutations: 2

References changed: 10.1093/annonc/mdy284.002.

Changed Rucaparib in Prostate cancer with BRCA2 Oncogenic mutations: 2

References changed: 10.1093/annonc/mdy284.002.

Changed Sorafenib in Gastrointestinal Stromal Tumour with KIT Oncogenic mutation, V654A, T670I, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P: 2

Comments changed: Not TGA approved; Not FDA approved. NCCN recommended 2ANot TGA approved; NCCN 2A. References changed: 10.1200/jco.2011.29.15_suppl.10009, 22270258, 2266552428021077.

Changed Panitumumab + Dabrafenib + Trametinib in Colorectal Cancer with BRAF V600E: 3

References changed: 29431699, 10.1093/annonc/mdw370.4.

Changed Pazopanib in Gastrointestinal Stromal Tumour with KIT Oncogenic mutation: 3

References changed: 27068858, 28021077.

Changed Imatinib, Sunitinib in Gastrointestinal Stromal Tumour with PDGFRA D842V: R1

References changed: 14645423, 22665524.

Changed Sunitinib in Gastrointestinal Stromal Tumour with KIT K642E, D816V, D820A, D816: R2

References changed: 19164557, 31085175, 30792533, 31123346, 30101284, 3127007819164557,31085175,30792533,31123346,30101284, 31270078.

Changed Sunitinib in Gastrointestinal Stromal Tumour with KIT R796G, C809G, D816F, D816G, D816H, D816V, D816, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840N: R2

References changed: 19164557, 22665524, 31085175, 30792533, 31123346, 30101284, 31270078, 10.1200/jco.2013.31.15_suppl.1051019164557,31085175,30792533,31123346,30101284, 31270078, 10.1200/jco.2013.31.15_suppl.10510.

Friday, 27 November 2020 (Version: 20201127AU)

New Olaparib in Prostate cancer with FANCL Oncogenic mutations: 4

PROFound trial inclusion criteria but no recruitment. References: 32343890

New Trametinib in Chronic myeloid leukaemia with LZTR1 Loss-of-function mutation: 4

LZTR1 lof mutation decreases RAS ubiquitination and is associated with resistance, reverted by MEK inhibitor in a CML model. References: 30442766

New AG-270 in Solid tumours with MTAP Deletion: 4

References: 10.1158/1538-7445.AM2020-309

New MEK inhibitor + JQ1 in Malignant peripheral nerve sheath tumor with NF1+SUZ12 NF1:loss-of-function mutation AND SUZ12:loss-of-function mutation: 4

References: 25119042

New JQ1 in Solid tumours with SUZ12 Loss-of-function mutation: 4

PRC2 loss sensitizes cancers to bromodomain inhibitors. References: 25119042

New Nilotinib, Dasatinib, Ponatinib in Chronic myeloid leukaemia with BAP1 Loss-of-function mutation: R2

Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance. References: 30442766

New Binimetinib + Encorafenib in Colorectal Cancer with KRAS Amplification: R2

Paired pre-post treatment sequencing. References: 25673644

New Dabrafenib + Panitumumab in Colorectal Cancer with KRAS Amplification: R2

Paired pre-post treatment sequencing. References: 25673644

New Imatinib, Ponatinib in Chronic myeloid leukaemia with LZTR1 Loss-of-function mutation: R2

Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance. References: 30442766

New Dabrafenib + Trametinib, Trametinib in Colorectal Cancer with MAP2K1 F53L: R2

Paired pre-post treatment sequencing. References: 25673644

New Imatinib, Nilotinib, Dasatinib, Bosutinib, Ponatinib in Chronic myeloid leukaemia with NF1 Loss-of-function mutation: R2

Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance. References: 30442766

New Imatinib, Nilotinib, Dasatinib, Ponatinib in Chronic myeloid leukaemia with PTPN11 Loss-of-function mutation: R2

Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance. References: 30442766

New Imatinib, Nilotinib, Dasatinib, Bosutinib, Ponatinib in Chronic myeloid leukaemia with WT1 Loss-of-function mutation: R2

Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance. References: 30442766

Removed Lapatinib in Breast Cancer with ERBB2 alterations Amplification: Tier 2

Removed EGFR inhibitor in Solid tumours with EGFR alterations Oncogenic mutations, Overexpression: Tier 4

Removed bispecific ERBB2/CD3 monoclonal antibody in Solid tumours with ERBB2 alterations Amplification: Tier 4

Removed JAK2 inhibitor in Solid tumours; Liquid Cancers with JAK2 alterations Oncogenic mutations: Tier 4

Removed KIT inhibitor in Solid tumours with KIT alterations Oncogenic mutations: Tier 4

Changed Tamoxifen in Breast cancer with ESR1 Protein expression: 1

Comments changed: Standard of care. For trial matching.

Changed Imatinib in Melanoma with KIT Exon 11 mutation, Exon 13 mutation, V559C, V560D, L576P, D820Y, K642E, N822K: 3

Comments changed: Not TGA approved; Not FDA approved; NCCN 2A; ASCO not recommended. 2 durable CR; 2 durable PR in Phase 2Not TGA approved; Not FDA approved; NCCN 2A; 2 durable CR; 2 durable PR.

Changed Imatinib in Melanoma with KIT Oncogenic mutations except Exon 17 mutation: 3

Comments changed: Not TGA approved; Not FDA approved; NCCN 2A; ASCO not recommended.

Changed CYP17A1 inhibitor in Gliomas with AR Protein expression: 4

Comments changed: Weak evidence. For trial matching only.

Changed Ribociclib in Rhabdomyosarcoma with CDK4 Amplification and NOT overexpression: 4

Comments changed: In PAX7-FOXO1 fusion-positive cell lineIn PAX7-FOXO1 fusion-positive cell line.

Changed Therapy in Solid tumours with ERBB2 : 4

Therapy changed: BTRC4017Aanti-ERBB2 monoclonal antibody. Alterations changed: Amplification; Overexpression. References changed: NCT03448042.

Changed ERBB2 inhibitor,exon 20 selective in Solid tumours with ERBB2 Exon 20 mutation, Exon 20 insertion: 4

Comments changed: For trial matching.

Changed Therapy in Solid tumours, Uveal Melanoma with GNA11 Oncogenic mutations: 4

Therapy changed: IDE196PKC inhibitor. Comments changed: For trial matching.

Changed Therapy in Solid tumours, Uveal Melanoma with GNAQ Oncogenic mutations: 4

Therapy changed: IDE196PKC inhibitor. Comments changed: For trial matching.

Changed Therapy in Solid tumours with KIT : 4

Therapy changed: LOP628anti-c-KIT antibody-drug conjugate. Alterations changed: OverexpressionOncogenic mutations. Comments changed: For trial matching.

Changed Sotorasib in Colorectal Cancer with KRAS G12C: 4

Comments changed: CODEBREAK 100. ORR 7%CODEBREAK 100 ORR 7%.

Changed Sotorasib in Solid tumours with KRAS G12C: 4

Comments changed: CODEBREAK 100. PR in pancreatic, endometrial, melanoma, appendiceal cancersCODEBREAK 100 responses seen in pancreatic, endometrial, melanoma, appendiceal cancer.

Changed MEK inhibitor, ERK inhibitor in Solid tumours with MAP2K1 Oncogenic mutations: 4

Comments changed: For trial matching.

Changed Therapy in Solid tumours with MAP2K4 Oncogenic mutations: 4

Therapy changed: SelumetinibMEK inhibitor.

Changed Therapy in Solid tumours with MAP3K1 Oncogenic mutations: 4

Therapy changed: SelumetinibMEK inhibitor.

Changed MET inhibitor in Solid tumours with MET Alteration: 4

Comments changed: For trial matching.

Changed Therapy in Solid tumours with MTAP Deletion: 4

Therapy changed: GSK3368715PRMT inhibitor,type 1. Comments changed: For trial matching.

Changed Everolimus in Urothelial Carcinoma with MTOR E2014K, E2419K: 4

Comments changed: Imported from OncoKB.

Changed RMC-4630 + Cobimetinib in Solid tumours with NF1 Oncogenic mutation: 4

Comments changed: Phase 1 trial.Phase 1..

Changed Therapy with NF1 Oncogenic mutations: 4

Therapy changed: TrametinibMEK inhibitor. Cancer type(s) changed: Non-small Cell Lung CancerSolid tumours

Changed Therapy in Glioblastoma with NOTCH2 Gain-of-function mutations: 4

Therapy changed: MRK003MRK-003.

Changed Therapy in Solid tumours with NOTCH2 Rearrangements: 4

Therapy changed: MRK003 + paclitaxelGamma secretase inhibitor + paclitaxel.

Changed Therapy in Non-small cell lung cancer with NOTCH3 Overexpression: 4

Therapy changed: MRK003Gamma secretase inhibitor.

Changed PARP inhibitor in Prostate cancer with PALB2 Oncogenic mutations: 4

Comments changed: TRITON2 trial.

Changed FOLFIRINOX in Pancreatic Adenocarcinoma with PALB2 Oncogenic mutations (germline): 4

Comments changed: Retrospective cohort study. Only 4 patients.Guideline NCCN.org.

Changed Therapy in Solid tumours with PRKCA Fusion: 4

Therapy changed: IDE196PKC inhibitor. Comments changed: For trial matching.

Changed Therapy in Solid tumours with PRKCB Fusion: 4

Therapy changed: IDE196PKC inhibitor. Comments changed: For trial matching.

Changed Therapy in Prostate cancer with PSMA Protein expression: 4

Therapy changed: BAY2010112PSMA bispecific T-cell engager.

Thursday, 26 November 2020 (Version: 20201126AU)

New Olaparib in Urothelial Carcinoma with KMT2C Loss-of-function mutations, Deletion: 4

Cell-line study suggesting that KMT2C loss may results in HRD-like defects and sensitive to olaparib. References: 30665945

Changed Goserelin in Breast cancer with ESR1 Protein expression: 1

Comments changed: Standard of care..

Changed Letrozole in Breast cancer with ESR1 Protein expression: 1

Comments changed: Standard of care. Restricted benefit. HR-positive MBC.

Changed Medroxyprogesterone Acetate in Breast cancer with ESR1 Protein expression: 1

Comments changed: Standard of care..

Changed Temozolomide in Glioblastoma with MGMT Promoter methylation: 1

Comments changed: Standard of care. NCCN Category 1..

Changed Tamoxifen, Letrozole, Anastrozole, Exemestane, Medroxyprogesterone Acetate, Goserelin in Breast cancer with PGR Protein expression: 1

Comments changed: Standard of care. For trial matching.

Changed Medroxyprogesterone Acetate in Endometrial Carcinoma with PGR Protein expression: 1

Comments changed: Standard of care. For trial matching.

Changed Imatinib in Melanoma with KIT

Alterations changed: Exon 11 mutation, Exon 13 mutation, V559C, V560D, L576P, D820Y, K642E, N822KExon 11 mutation, V559C, V560D, L576P, D820Y, K642E, N822K. Tier changed: 32. Comments changed: Not TGA approved; Not FDA approved; NCCN 2A; 2 durable CR; 2 durable PRNot TGA approved; FDA approved; NCCN 2A.

Changed Imatinib in Melanoma with KIT

Alterations changed: Oncogenic mutations except Exon 17 mutationOncogenic mutations except D816. Tier changed: 32. Comments changed: Not TGA approved; Not FDA approved; NCCN 2ANot TGA approved; FDA approved; NCCN 2A.

Changed Vismodegib, Sonidegib in Basal Cell Carcinoma, Solid tumours with SMO D473G, D473Y, D473H, G497W, V321M, W281L, Q477E, A327P, C390R, D506N, E181K, E481G, G453D, K519R, K564E, L221P, L353F, N476K, P513L, P698T, P739L, P739S, R168H, R199Q, T336I, T349I, T349P, T534I, T548I, T640A, V386A, V404M, V414A, A459V, D384N, E518K, I408V, N219D, S387N, T241M, V281C: R2

References changed: 21771911, 25759019, 25759020, 3112590721771911, 25759019, 31125907.

Friday, 20 November 2020 (Version: 20201120AU)

New Lapatinib in Urothelial Carcinoma with ERBB2 Overexpression: R2

References: 28034079

New Pembrolizumab in Colorectal Cancer with POLE P286R: 4

Complete response. References: 10.1200/PO.18.00214

New Vandetanib in Solid tumours with RET G810A: R2

References: 27496134, 32083997

New Vandetanib in Solid tumours with RET S904F: R2

References: 29434222, 32083997

New Ponatinib in Solid tumours with RET I788N: 4

References: 28615362

New Vandetanib, Cabozantinib in Solid tumours with RET V804L, V804M: R2

Gatekeeper mutation. References: 15184865, 27496134, 32083997

New Ponatinib in Thyroid Cancer with RET V804L, V804M: 4

Gatekeeper mutation. Thyroid cancer cell lines. References: 23811235

New Selpercatinib, Pralsetinib in Solid tumours with RET V804L, V804M: 4

Gatekeeper mutation. References: 32083997

New Ponatinib, Lenvatinib in Solid tumours with RET G810A: 4

References: 32083997

New Selpercatinib, Pralsetinib in Solid tumours with RET G810S, G810R: R2

References: 10.1093/annonc/mdz244.068, 32083997

New TPX-0046 in Solid tumours with RET G810S, G810R: 4

References: 10.1093/annonc/mdz244.068, 32083997

New Cabozantinib in Solid tumours with MDM2 Amplification: R2

Anti-RET activity. References: 32083997

New Ponatinib in Solid tumours with NRAS Q61K: R2

Anti-RET activity. References: 32083997

New Vandetanib in Medullary Thyroid Cancer with RET M918T: 4

ZETA trial. References: 32584630, 32083997

New Cabozantinib in Medullary Thyroid Cancer with RET M918T, Oncogenic mutations: 4

Exploratory analysis of EXAM trial, but lack of OS benefit even in patients subsequently received an MKI. References: 27525386, 29045520

New Vandetanib in Non-Small Cell Lung Cancer with RET Fusions: 3

LURET. Single-arm phase 2. ORR 47%. PFS 4.7mo. References: 27825636

New Vandetanib in Non-Small Cell Lung Cancer with RET Fusions: 3

Single-arm phase 2. ORR 18%. PFS 4.5mo. References: 27803005

New Lenvatinib in Non-Small Cell Lung Cancer with RET Fusions: 3

Single-arm phase 2. ORR 16%. PFS 7.3mo. References: 31710864

New Agerafenib in Non-Small Cell Lung Cancer with RET KIF5B-RET fusion: R2

References: 31710864

New Agerafenib in Non-Small Cell Lung Cancer with RET RET fusions and NOT KIF5B-RET fusion: 4

References: 31710864

New Gefitinib + Gemcitabine in Solid tumours with EGFR+ERRFI1 EGFR:overexpression AND ERRFI1: 4

Cell line study of effect of EFFRI1. EGFR inhibition sensitises cell to chemotherapy. References: 29335246

New MK-2206 + Gemcitabine in Solid tumours with EGFR+ERRFI1 EGFR:low expression AND ERRFI1: 4

Cell line study of effect of EFFRI1. AKT inhibitor sensitises cell to chemotherapy. References: 29335246

New Erlotinib in Cholangiocarcinoma with ERRFI1 E384X, Loss-of-function mutation, deletion: 4

Case report. References: 24550739

Tuesday, 17 November 2020 (Version: 20201117AU)

New Toripalimab in Gastric cancer with CD274 Protein expression: 4

ORR 37 v 8% in tumour cell. SP142. Cutoff 1%. References: 31236579

New Toripalimab in Gastric cancer with Tumour Mutational Burden High: 4

Exploratory analysis showed ORR 33 v 6% at TMB threshold of 12/MB. References: 31236579

New Buparlisib in Urothelial Carcinoma with TSC1 Oncogenic mutations: R2

References: 32767682

New Buparlisib + Tamoxifen in Breast Cancer with PIK3CA Oncogenic mutations: 4

PIKTAM trial. ORR 40% but stoped prematurely due to toxicity. References: 32352244

New Taselisib in Breast Cancer with PIK3CA E542K and E453, E542K and E726K, E542K and M1043, E545K and E453, E545K and E726, E542K and M1043, H1047R and E453, H1047R and E726K: 4

Double PIK3CA mutations in cis. References: 31699932

New Buparlisib + Fulvestrant in Breast Cancer with PIK3CA Oncogenic mutations: 3

PFS 4.7 v 1.4 mo HR 0.39. Retrospective biomarker analysis. References: 29508760

New Pictilisib + Paclitaxel in Breast Cancer with PIK3CA Oncogenic mutations: R2

PEGGY. No PFS improvement over placebo. Similar ORR. References: 27573562

New Pictilisib + Fulvestrant in Breast Cancer with PIK3CA Oncogenic mutations: R2

FERGI. PIK3CA mutation status had no effect on benefit. References: 27155741

Changed Larotrectinib in Solid tumours with NTRK1 Fusions: 1B

References changed: 29466156, 32105622, 10.1200/JCO.2019.37.15_suppl.1001029466156, 10.1200/JCO.2019.37.15_suppl.10010.

Changed Larotrectinib in Solid tumours with NTRK2 Fusions: 1B

References changed: 29466156, 32105622, 10.1200/JCO.2019.37.15_suppl.1001029466156, 10.1200/JCO.2019.37.15_suppl.10010.

Changed Larotrectinib in Solid tumours with NTRK3 Fusions: 1B

References changed: 29466156, 32105622, 10.1200/JCO.2019.37.15_suppl.1001029466156, 10.1200/JCO.2019.37.15_suppl.10010.

Changed Therapy in Gastric cancer with RICTOR Amplification: 4

Therapy changed: VistusertibAZD2014.

Changed GSK2636771 in Solid tumours with PTEN Loss-of-function mutation, loss of protein expression: R2

References changed: 10.1093/annonc/mdy279.406.

Wednesday, 11 November 2020 (Version: 20201111AU)

New Tremelimumab in Solid tumours with Tumour Mutational Burden High: 4

References: ACTRN12620000918921

Changed Larotrectinib in Solid tumours with NTRK2 Fusions: 1B

Comments changed: TGA approved. Not PBS reimbursedNot TGA approved.

Changed Larotrectinib in Solid tumours with NTRK3 Fusions: 1B

Comments changed: TGA approved. Not PBS reimbursedNot TGA approved.

Changed Ripretinib in Gastrointestinal Stromal Tumour with PDGFRA Oncogenic mutations

Tier changed: 1B2. Comments changed: Not TGA approved; FDA approved; NB Pre-specified group in original trial, but only 3 cases were included in INVICTUS..

Changed Entrectinib in Non-Small Cell Lung Cancer with ROS1 Fusions

Tier changed: 1B2. Comments changed: TGA approved; Not PBS ReimbursedNot TGA approved; FDA approved.

Changed Lorlatinib in Non-Small Cell Lung Cancer with ROS1 Fusions

Tier changed: 1B2.

Changed Sorafenib in Acute Myeloid Leukaemia with FLT3 Internal tandem duplication: 2

Comments changed: Not TGA approved for AML. In allogeneic SCT population. 1Y Relapse 7% vs 24.5%.

Changed Regorafenib in Gastrointestinal Stromal Tumour with PDGFRA D842V, Exon 18 mutation: 2

Comments changed: Not TGA approved; NCCN Category 1 but not selected based on PDGFRA mutationNot TGA approved; NCCN Category 1 but biomarker unselected.

Tuesday, 10 November 2020 (Version: 20201110AU)

New CH5126766 in Solid tumours with KRAS G12: 4

References: 33128873

New Palbociclib in Lung Squamous Cell Carcinoma with CCND1 Amplification: R2

Lung-MAP S1400C, ORR 6%. References: 31302234, 33125909

New Palbociclib in Lung Squamous Cell Carcinoma with CCND2 Amplification: R2

Lung-MAP S1400C, ORR 6%. References: 31302234, 33125909

New Palbociclib in Lung Squamous Cell Carcinoma with CCND3 Amplification: R2

Lung-MAP S1400C, ORR 6%. References: 31302234, 33125909

New Palbociclib in Lung Squamous Cell Carcinoma with CDK4 Amplification: R2

Lung-MAP S1400C, ORR 6%. References: 31302234, 33125909

New Palbociclib in Lung Squamous Cell Carcinoma with CDK6 Amplification: R2

Lung-MAP S1400C, ORR 6%. References: 31302234, 33125909

New AZD4547 in Lung Squamous Cell Carcinoma with FGFR1 Alteration: R2

Lung-MAP S1400D. References: 31195180, 33125909

New AZD4547 in Lung Squamous Cell Carcinoma with FGFR3 Alteration: R2

Lung-MAP S1400D. References: 31195180, 33125909

New Telisotuzumab Vedotin in Lung Squamous Cell Carcinoma with MET Overexpression: R2

Lung-MAP S1400K, Selected based on H-Score (>150). ORR 9%. References: 33125909, 10.1200/JCO.2019.37.15_suppl.9075

New Taselisib in Lung Squamous Cell Carcinoma with PIK3CA Oncogenic mutation: R2

Lung-MAP S1400B, ORR 5%. References: 31158500, 33125909

Changed Entrectinib in Solid tumours with NTRK1 Fusions

Tier changed: 1B2.

Changed Larotrectinib in Solid tumours with NTRK1 Fusions

Tier changed: 1B2. Comments changed: TGA approved. Not PBS reimbursedNot TGA approved.

Changed Entrectinib in Solid tumours with NTRK2 Fusions

Tier changed: 1B2.

Changed Larotrectinib in Solid tumours with NTRK2 Fusions

Tier changed: 1B2.

Changed Entrectinib in Solid tumours with NTRK3 Fusions

Tier changed: 1B2.

Changed Larotrectinib in Solid tumours with NTRK3 Fusions

Tier changed: 1B2.

Changed Tazemetostat in Epithelioid sarcoma with SMARCB1 : 2

Alterations changed: Loss of protein expression, deletion. Comments changed: Not TGA approved. T3 but FDA approved. NCT02601950Not TGA approved. FDA approved. NCT02601950. References changed: 33035459, 10.1200/JCO.2019.37.15_suppl.11003.

Changed Olaparib in Breast Cancer with BRCA1 Oncogenic mutations: 3

References changed: 33119476, 10.1200/JCO.2020.38.15_suppl.1002.

Changed Olaparib in Breast Cancer with BRCA2 Oncogenic mutations: 3

References changed: 33119476, 10.1200/JCO.2020.38.15_suppl.1002.

Changed Olaparib in Breast Cancer with PALB2 Oncogenic mutations (germline): 3

References changed: 33119476, 10.1200/JCO.2020.38.15_suppl.1002.

Changed Olaparib in Breast Cancer with ATM Oncogenic mutations: R2

References changed: 33119476, 10.1200/JCO.2020.38.15_suppl.1002.

Changed Olaparib in Breast Cancer with CHEK2 Oncogenic mutations: R2

References changed: 33119476, 10.1200/JCO.2020.38.15_suppl.1002.

Tuesday, 3 November 2020 (Version: 20201103AU)

New TPX-0022 in Solid tumours with MET Alterations: 4

References: 10.1016/S0959-8049(20)31074-1

New Adagrasib in Non-Small Cell Lung Cancer, Colorectal Cancer, Solid tumours with KRAS G12C: 3

KRYSTAL-1. Combined Phase 1&2. ORR 45% (NSCLC), 17% (CRC). References: 10.1016/S0959-8049(20)31076-5

New Fadraciclib in Ovarian cancer with CCNE1 Amplification: 4

Phase 1. 1 Case of SD. References: 10.1016/S0959-8049(20)31086-8

New Fadraciclib in Endometrial Carcinoma with MCL1 Amplification: 4

References: 10.1016/S0959-8049(20)31086-8

New RMC-4630 + Cobimetinib in Solid tumours with KRAS G12, Amplification: 4

Phase 1. References: 10.1016/S0959-8049(20)31089-3

New RMC-4630 + Cobimetinib in Solid tumours with NF1 Oncogenic mutation: 4

Phase 1. References: 10.1016/S0959-8049(20)31089-3

New RMC-4630 + Cobimetinib in Solid tumours with BRAF D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, G469, G469E, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R: 4

Phase 1. References: 10.1016/S0959-8049(20)31089-3

New Seribantumab in Solid tumours with NRG1 Fusion: 4

References: 10.1158/1535-7163.TARG-19-PR02

New Seribantumab + Docetaxel in Non-Small Cell Lung Cancer with NRG1 Overexpression: R2

No PFS improvement in EGFR wt NSCLC. References: 10.1200/JCO.2019.37.15_suppl.9036

New Infigratinib in Cholangiocarcinoma with FGFR2 E565A, L617M: R2

References: 31911531

New Futibatinib in Cholangiocarcinoma with FGFR2 N550, V565, E565A, C492: R2

References: 10.1016/S0959-8049(20)31121-7

Changed Therapy in Non-Small Cell Lung Cancer with KRAS G12C: 3

Therapy changed: SotorasibAMG-510.

Changed PLX8394 in Solid tumours with BRAF L597, L597Q, K601, K601E: 4

References changed: 10.1158/1535-7163.TARG-17-B176, 10.1016/S0959-8049(20)31078-9.

Changed Therapy in Colorectal Cancer with KRAS G12C: 4

Therapy changed: SotorasibAMG-510.

Changed Therapy in Solid tumours with KRAS G12C: 4

Therapy changed: SotorasibAMG-510.

Changed Milademetan Tosylate in Solid tumours with MDM2 : 4

Alterations changed: Amplification, Overexpression. References changed: 10.1200/JCO.2018.36.15_suppl.11514, 10.1016/S0959-8049(20)31080-7.

Saturday, 31 October 2020 (Version: 20201031AU)

New MEK inhibitor + SHP2 inhibitor in Solid tumours with KRAS Oncogenic mutations: 4

References: 29808009, 30045908, 31068384, 31439712

New SHP099 + Trametinib, SHP099 + Ulixertinib in Neuroblastoma with NRAS Q61K: 4

References: 32586982

New SHP099, II-B08, RMC-4550 in Neuroblastoma with NRAS Q61K: R2

References: 32586982

New SHP099 in Solid tumours with PTPN11 P491Q: R2

Cell line data. References: 30045908

Thursday, 29 October 2020 (Version: 20201029AU)

Changed Palbociclib in Dedifferentiated Liposarcoma with CDK4 Amplification

Tier changed: 32. Comments changed: NCCN 2A. OncoKB LOE 2Not TGA approved; NCCN 2A. References changed: 23569312, 27124835.

Changed Palbociclib in Well-Differentiated Liposarcoma with CDK4 Amplification

Tier changed: 32. Comments changed: NCCN 2A. OncoKB LOE 2Not TGA approved; NCCN 2A. References changed: 23569312, 27124835.

Changed Cisplatin, Carboplatin, Platinum-based antineoplastic agent in Ovarian cancer with EMSY Amplification; Overexpression: 4

Comments changed: Retrospective High grade ovarian cancer; Functional HR-deficient phenotypeRetrospectivie High grade ovarian cancer; Functional HR-deficient phenotype.

Wednesday, 28 October 2020 (Version: 20201028AU)

Changed Capivasertib + Fulvestrant in Breast Cancer with AKT1 E17K

Tier changed: 43. Comments changed: Phase 1 study. ORR 36%..

Tuesday, 27 October 2020 (Version: 20201027AU)

New Cisplatin, Carboplatin, Platinum-based antineoplastic agent in Ovarian cancer with EMSY Amplification; Overexpression: 4

Retrospectivie High grade ovarian cancer; Functional HR-deficient phenotype. References: 31154673

New LY3295668 in Neuroblastoma with MYCN Amplification; Overexpression: 4

References: NCT04106219; 10.1200/JCO.2020.38.15_suppl.TPS10561

New LY3295668 in Solid tumours with RB1 Oncogenic mutations, Loss-of-function mutation, loss of protein expression: 4

References: 30373917

Changed Cetuximab in Breast Cancer, Triple-Negative Breast Cancer with EGFR Amplification: 4

Comments changed: Case report. Triple-Negative Breast Cancer.

Thursday, 22 October 2020 (Version: 20201022AU)

New Veliparib in Non-Small Cell Lung Cancer with FANCD2 Loss-of-function mutation, Oncogenic mutations: 4

Cell line study only using FANCD2 knockout. References: 25566506

Wednesday, 21 October 2020 (Version: 20201021AU)

New Olaparib, Rucaparib in Ovarian cancer with RAD50 Oncogenic mutations; Deletions: 4

Cell line study. References: 27016230

New Pembrolizumab in Cervical cancer with CD274 Loss of protein expression: R2

KEYNOTE-028. ORR 0% in PD-L1 negative population. References: 30943124

Changed Cetuximab with EGFR Amplification: 4

Cancer type(s) changed: Breast Cancer, Triple-Negative Breast Cancer Comments changed: Triple-Negative Breast Cancer.

Friday, 16 October 2020 (Version: 20201016AU)

New mRNA-5671 in Solid tumours with KRAS G12D, G12V, G13D, G12C: 4

References: NCT03948763

Removed Venetoclax in Solid tumours with BCL2L1 alterations Amplification: Tier 4

Changed Therapy in Glioma, Glioblastoma with EGFR : 4

Therapy changed: AMG-596, anti-EGFRvIII/CD3_BiTE_antibody. Alterations changed: vIII variant.

Changed Depatuxizumab Mafodotin in Glioma, Glioblastoma with EGFR : 4

Alterations changed: vIII variant.

Changed Bemarituzumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with FGFR2 : 4

Alterations changed: Overexpression, amplification.

Changed Therapy in Colorectal Cancer with KRAS Oncogenic mutations: 4

Therapy changed: Onvansertib + FOLFIRI + Bevacizumab, Onvansertib.

Tuesday, 13 October 2020 (Version: 20201013AU)

New Everolimus + Docetaxel in Urothelial Carcinoma with NF2 Loss-of-function mutation: 4

Case report. References: 25630452

Changed Binimetinib in Melanoma with NRAS Oncogenic mutations

Tier changed: 32. Comments changed: Not TGA approved. Positive Phase III NEMO result, but overall small absolute PFS gain. FDA application withdrawn and NCCN 2B. Revised Tier 3Not TGA approved. Phase III. NEMO. Note small absolute PFS gain.

Thursday, 8 October 2020 (Version: 20201008AU)

New Cisplatin, Platinum-based antineoplastic agent in Mesothelioma, Ovarian cancer, Cervical cancer with ERCC1 Loss of protein expression; Oncogenic mutations: 4

References: 22031231, 19574766, 16144907, 32564128, 28659181

Changed Therapy in Urothelial Carcinoma with ERCC2 Oncogenic mutations: 4

Therapy changed: Cisplatin, Platinum-based antineoplastic agent.

Wednesday, 7 October 2020 (Version: 20201007AU)

New Sorafenib in Acute Myeloid Leukaemia with FLT3 Internal tandem duplication: 3

SORMAIN trial. Maintenance treatment. 24 months RFS 53.3% vs 85% placebo. References: 32673171

New M6620 in Solid tumours with ARID1A Oncogenic mutations: 4

1 CR from NCT02157792, with ATM loss. References: 32568634

New Osimertinib + Necitumumab in Non-Small Cell Lung Cancer with EGFR Exon 19 deletion and amplification; L858R and amplification; Exon 21 mutation and amplification: 4

ORCHARD trial. References: NCT03944772, NCT02496663

New Osimertinib + Crizotinib, Osimertinib + Alectinib in Non-Small Cell Lung Cancer with EGFR+ALK EGFR:oncogenic mutation and ALK:fusion: 4

Two case reports. References: 30957057

New Osimertinib + Ado-Trastuzumab Emtansine in Non-Small Cell Lung Cancer with EGFR+ERBB2 EGFR:oncogenic mutation and ERBB2:amplification: 4

References: NCT03784599

New Osimertinib + Pralsetinib in Non-Small Cell Lung Cancer with EGFR+RET EGFR:oncogenic mutation and RET:fusion: 4

Two case reports. References: 30257958

New Osimertinib + Crizotinib in Non-Small Cell Lung Cancer with EGFR+ROS1 EGFR:oncogenic mutation and ROS1:fusion: 4

Case report. References: 29935846

New Trastuzumab in Breast Cancer with ERBB2 D769H, I767N, R678Q, S310F, S310Y: 4

References: 32256585

New Neratinib, Afatinib in Breast Cancer with ERBB2 L755S, V777L, D769H, I767M, R678Q, S310F, S310Y: 4

References: 32256585

New Fam-trastuzumab deruxtecan-nxki in Breast Cancer with ERBB2 protein expression and NOT amplification: 4

DESTINY-Breast04. References: 32058843

New Lapatinib in Breast Cancer with ERBB2 V777L, D769H, I767N, Q678Q, S310F, S310Y: 4

References: 32256585

New Cobimetinib in Histiocytosis with KRAS G12R: 4

Case report. References: 29236635

New Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+ALK EGFR:oncogenic mutation and ALK:fusion: R2

References: 30957057

New Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+RB1 EGFR:oncogenic mutation and RB1:oncogenic mutation: R2

Small-cell transformation. References: 25758528, 30550363

New Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+RET EGFR:oncogenic mutation and RET:fusion: R2

References: 30257958, 30957057

New Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+ROS1 EGFR:oncogenic mutation and ROS1:fusion: R2

References: 29935846

New Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-Small Cell Lung Cancer with EGFR+TP53 EGFR:oncogenic mutation and TP53:oncogenic mutation: R2

Small-cell transformation. References: 30550363

New Trastuzumab in Breast Cancer with ERBB2 L755S, D769Y, V842I, K753E: R2

References: 32256585

New Lapatinib in Breast Cancer with ERBB2 L755S, V842I, K753E: R2

References: 32256585

New Tucatinib in Breast Cancer with ERBB2 L755S: R2

References: 10.1158/1538-7445.AM2020-1911

New LY2874455 in Liposarcoma with FRS2 Amplification: 4

References: 30795553

Changed Neratinib + Capecitabine in Breast Cancer with ERBB2 Amplification: 2

Comments changed: Not TGA approved. FDA approved. NALA. PFS superior over lapatinib.

Changed Ripretinib in Gastrointestinal Stromal Tumour with KIT Oncogenic mutations: 2

References changed: 31085175, 32511981, 32804590, 10.1158/1538-7445.AM2018-392531085175, 32511981, 10.1158/1538-7445.AM2018-3925.

Changed Ripretinib in Gastrointestinal Stromal Tumour with PDGFRA Oncogenic mutations: 2

References changed: 32511981, 32804590.

Saturday, 3 October 2020 (Version: 20201003AU)

New Pembrolizumab in Solid tumours except Colorectal Cancer with Tumour Mutational Burden High: 3

Not TGA approved. KEYNOTE-158. FDA approved although overall Tier 3, H v nonH: ORR 29% v 6% in a Phase 2 study. References: 32919526

New Pembrolizumab in Colorectal Cancer with Tumour Mutational Burden High: 4

KEYNOTE-158 did not include MSS colorectal cancers. References: 32919526

New Vemurafenib in Colorectal Cancer with BRAF V600: R2

VE-BASKET. References: 26287849

Changed Pembrolizumab with Tumour Mutational Burden High: 2

Cancer type(s) changed: Cervical cancer, Endometrial cancer, Neuroendocrine tumour, Salivary gland carcinoma, Small-cell lung cancer, Thyroid cancer, Vulvar cancerSolid tumours Comments changed: Not TGA approved. KEYNOTE-158. The following cancer types have higher ORR in TMB-H cohort (vs non-TMB-H)Not TGA approved. KEYNOTE-158. Tier 3 (H v nonH: ORR 29% v 6% in Phase 2 study) but FDA approved..

Friday, 2 October 2020 (Version: 20201002AU)

New Dinaciclib + MK2206 in Ovarian cancer with CCNE1 Amplification: 4

High grade ovarian cancer. References: 27663592

New SNS-032 in Ovarian cancer with CCNE1 Amplification: 4

High grade ovarian cancer. References: 26204491

Wednesday, 30 September 2020 (Version: 20200930AU)

New Veliparib in Pancreatic Adenocarcinoma with BRCA1 Oncogenic mutations (germline): R2

Single-agent has no confirmed response. References: 31976786

New Veliparib in Pancreatic Adenocarcinoma with BRCA2 Oncogenic mutations (germline): R2

Single-agent has no confirmed response. References: 31976786

New Nivolumab + FOLFOX, Nivolumab + CAPOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CD274 Protein expression: 2

CheckMate 649 study. CPS more than 5. References: 10.1016/j.annonc.2020.08.2296

New Pembrolizumab + Cisplatin + Fluorouracil in Oesophageal Cancer, Oesophageal Adenocarcinoma, Oesophageal Squamous Cell Carcinoma with CD274 Protein expression: 2

KEYNOTE-590. CPS cutoff 10. References: 10.1016/j.annonc.2020.08.2298

New Cemiplimab in Non-Small Cell Lung Cancer with CD274 Protein expression: 2

EMPOWER-Lung 1. CPS >= 50. References: 10.1016/j.annonc.2020.08.2285

Changed Therapy in Solid tumours with Tumour Mutational Burden High: 3

Therapy changed: Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody.

Changed Therapy in Solid tumours with LRP1B Oncogenic mutation: 4

Therapy changed: Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody.

Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Solid tumours with POLE Oncogenic mutations: 4

References changed: 31415061, 10.1200/JCO.2020.38.15_suppl.3008, 27486176.

Changed Therapy in Solid tumours with Tumour Mutational Burden High: 4

Therapy changed: Anti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, immune checkpoint blockade,PD-1 targeting, immune checkpoint blockade,PD-L1 targetingAnti-PD1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, Anti-CTLA-4 monoclonal antibody, immune checkpoint blockade,PD-1 targeting, immune checkpoint blockade,PD-L1 targeting, immune checkpoint blockade,CTLA-4 targeting.

Monday, 28 September 2020 (Version: 20200928AU)

New Futibatinib in Solid tumours with FGFR1 N546D: 4

FOENIX-101. ORR 11% in qd cohort. References: 32622884

New Futibatinib in Solid tumours with FGFR2 Fusions: 4

FOENIX-101. ORR 11% in qd cohort. References: 32622884

New Amivantamab in Non-Small Cell Lung Cancer with EGFR Exon 20 insertion: 4

CHRYSALIS. ORR 36%. References: 32414908, 10.1200/JCO.2020.38.15_suppl.9512

New Amivantamab + Lazertinib in Non-Small Cell Lung Cancer with EGFR Exon 19 deletion, L858R: 3

ORR 36% 15PR 1CR in osimertinib resistance cohort. ORR 100% treatment naive. References: 10.1016/j.annonc.2020.08.1572

New Apatinib + Gefitinib in Non-Small Cell Lung Cancer with EGFR Exon 19 deletion, L858R: 2

Apatinib not TGA or FDA approved. ACTIVE Phase 3 trial. References: 10.1016/j.annonc.2020.08.2283

Changed Lorlatinib in Non-Small Cell Lung Cancer with ALK EML4-ALK Fusion, Fusions: 1B

Comments changed: TGA approved. Not PBS reimbursed. Ph3 CROWN. References changed: 30413378, 10.1016/j.annonc.2020.08.2282.

Changed Ipatasertib + Abiraterone in Prostate cancer with PTEN Loss of protein expression; Loss-of-function mutation: 2

References changed: NCT03072238, 10.1016/j.annonc.2020.08.2250NCT03072238, ESMO 2020 LBA4.

Changed Palbociclib + Letrozole in Endometrioid endometrial cancer, Endometrial cancer with ESR1 Protein expression: 3

References changed: 10.1016/j.annonc.2020.08.2258NCT02730429.

Changed TK216 + Vincristine in Ewing Sarcoma with FLI1 EWSR1-FLI1 Fusion: 4

References changed: NCT02657005, 10.1016/j.annonc.2020.08.1846NCT02657005, ESMO 2020 1620O.

Wednesday, 23 September 2020 (Version: 20200923AU)

Removed PORCN inhibitor in Solid tumours with APC alterations Oncogenic mutation: Tier 4

Changed Avapritinib in Gastrointestinal Stromal Tumour with PDGFRA Exon 18 mutation, D842V, D842_H845del: 2

Comments changed: Not TGA approved; FDA approved. NAVIGATOR trial; First-line.

Tuesday, 22 September 2020 (Version: 20200922AU)

New Avelumab in Urothelial Carcinoma with CD274 Protein expression: 2

Not TGA approved. FDA Approved. JAVELIN Bladder 100. Maintenance. PD-L1 negative group also has benefit but less in magnitude. References: 32945632

New Sorafenib in Acute Myeloid Leukaemia with FLT3 Internal tandem duplication: 2

In allogeneic SCT population. 1Y Relapse 7% vs 24.5%. References: 32791048

New Ripretinib in Gastrointestinal Stromal Tumour with PDGFRA Oncogenic mutations: 2

Not TGA approved; FDA approved; NB Pre-specified group in original trial, but only 3 cases were included in INVICTUS. References: 32511981

New Ipatasertib + Abiraterone in Prostate cancer with PTEN Loss of protein expression; Loss-of-function mutation: 2

IPATential150. Predefined NGS concordant with IHC. References: NCT03072238, ESMO 2020 LBA4

New Dabrafenib + Trametinib in Biliary Tract Cancers with BRAF V600E: 3

ROAR. BICR ORR 47%. References: 32818466

New Durvalumab + Olaparib in Breast Cancer with BRCA1 Oncogenic mutations (germline): 3

MEDIOLA. ORR 63%. References: 32771088

New Durvalumab + Olaparib in Breast Cancer with BRCA2 Oncogenic mutations (germline): 3

MEDIOLA. ORR 63%. References: 32771088

New Palbociclib + Letrozole in Endometrioid endometrial cancer, Endometrial cancer with ESR1 Protein expression: 3

ESMO 2020 LBA28. NSGO-PALEO / ENGOT-EN3. References: NCT02730429

New Azacitidine + Venetoclax in Acute Myeloid Leukaemia with IDH1 Oncogenic mutation: 3

Exploratory biomarker subgroup in Ph3 VIALE-A. OS HR 0.34 vs Azacitidine alone. References: 32786187

New Azacitidine + Venetoclax in Acute Myeloid Leukaemia with IDH2 Oncogenic mutation: 3

Exploratory biomarker subgroup in Ph3 VIALE-A. OS HR 0.34 vs Azacitidine alone. References: 32786187

New Ibrutinib in Chronic Lymphocytic Leukemia with TP53 Alteration: 3

CR 30%. References: 32726539

New Sacituzumab Govitecan in Triple-negative breast cancer with TACSTD2 Protein expression: 4

PFS Trop-2 staining higher in expressors. References: 28291390

Changed Sacituzumab Govitecan in Triple-negative breast cancer: 2

Biomarker changed: ESR1+ERBB2TACSTD2. Alterations changed: NOT ESR1:protein expression and NOT ERBB2:amplified. Comments changed: Not TGA approved; FDA approved. Anti Trop-2 ADC.

Changed Capmatinib in Non-Small Cell Lung Cancer with MET : 2

Alterations changed: Amplification, Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation. References changed: 32877583, 10.1200/JCO.2019.37.15_suppl.9004.

Changed Regorafenib in Gastrointestinal Stromal Tumour with PDGFRA D842V, Exon 18 mutation: 2

Comments changed: Not TGA approved; NCCN Category 1 but biomarker unselectedNot TGA approved; NCCN 1 but biomarker unselected. References changed: NCCN:sarcoma.

Changed Avapritinib in Gastrointestinal Stromal Tumour with PDGFRA Exon 18 mutation, D842V, D842_H845del: 2

Comments changed: Not TGA approved; FDA approved. NAVIGATOR trial. References changed: 32615108, 10.1200/JCO.2019.37.15_suppl.11022.

Changed Selpercatinib in Non-Small Cell Lung Cancer with RET Fusions: 2

Comments changed: Not TGA approved. LIBRETTO-001. 1L ORR 85%. References changed: 32846061, 10.1200/JCO.2020.38.15_suppl.3584.

Changed Selpercatinib in Medullary Thyroid Cancer with RET Oncogenic mutations and NOT Amplification, Fusions, M918T, V804M, V804L, C609, C611, C618, C620, C630, C634, D631_L633delinsE, E632_L633del, A883F, D631_L633delinsV, L790F, D898_E901del, D903_S904delinsEP, K666N T636_V637insCRT, D378_G385delinsE: 2

Comments changed: Not TGA approved. LIBRETTO-001. ORR 69%.

Changed Pembrolizumab in Solid tumours with Tumour Mutational Burden High: 2

Comments changed: Not TGA approved. KEYNOTE-158. Tier 3 (H v nonH: ORR 29% v 6% in Phase 2 study) but FDA approved.Not TGA approved. FDA approved. KEYNOTE-158. References changed: 32919526NCT02628067.

Changed AMG-510 in Non-Small Cell Lung Cancer with KRAS G12C: 3

Comments changed: CODEBREAK 100 ORR 32.2%. References changed: 32955176, 10.1016/j.jtho.2019.09.020.

Changed Tepotinib in Non-Small Cell Lung Cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 3

Comments changed: VISION trial. ORR 48%. All lines of therapy..

Changed Therapy in Ewing Sarcoma with FLI1 EWSR1-FLI1 Fusion: 4

Therapy changed: TK216 + Vincristine. Comments changed: CBR 62%OncoKB LOE 4 (Concordant tier). References changed: NCT02657005, ESMO 2020 1620O.

Changed AMG-510 in Colorectal Cancer with KRAS G12C: 4

Comments changed: CODEBREAK 100 ORR 7%Ongoing phase I. References changed: 32955176, 10.1200/JCO.2020.38.15_suppl.4018.

Changed AMG-510 in Solid tumours with KRAS G12C: 4

Comments changed: CODEBREAK 100 responses seen in pancreatic, endometrial, melanoma, appendiceal cancerOngoing phase I. References changed: 32955176, 10.1200/JCO.2020.38.15_suppl.3511, 10.1200/JCO.2020.38.15_suppl.TPS3661.

Sunday, 20 September 2020 (Version: 20200920AU)

New Imatinib in Melanoma with KIT Exon 11 mutation, V559C, V560D, L576P, D820Y, K642E, N822K: 2

Not TGA approved; FDA approved; NCCN 2A. References: 21642685, 16908931, 23416972

New Lapatinib in Breast Cancer with ERBB3 F94L, G284R, D297Y, T355I, E1261A: R2

In ER-positive HER2-positive cell line. References: 29963236

Removed JAK1-selective inhibitor in Solid tumours with JAK1 alterations Oncogenic mutations: Tier 4

Changed Imatinib in Melanoma with KIT : 2

Alterations changed: Oncogenic mutations except D816Oncogenic mutations, Exon 11 mutation, V559C, V560D, L576P, D820Y, K642E, N822K. References changed: 21642685, 16908931, 23416972.

Changed Imatinib in Gastrointestinal Stromal Tumour with KIT : R2

Alterations changed: A502_Y503dup, V560D, T670I, D816F, D816V, D816, D820AA502_Y503dup, V560D, T670I, D816F, D816V, D820A.

Changed Sorafenib in Gastrointestinal Stromal Tumour with KIT : R2

Alterations changed: D816F, D816G, D816H, D816V, D816.

Changed Axitinib in Gastrointestinal Stromal Tumour with KIT : R2

Alterations changed: D816V, D816H, D816.

Changed Sunitinib in Gastrointestinal Stromal Tumour with KIT : R2

Alterations changed: K642E, D816V, D820A, D816.

Changed Sunitinib in Gastrointestinal Stromal Tumour with KIT : R2

Alterations changed: R796G, C809G, D816F, D816G, D816H, D816V, D816, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840NR796G, C809G, D816F, D816G, D816H, D816V, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840N.

Changed Regorafenib in Gastrointestinal Stromal Tumour with KIT : R2

Alterations changed: V654A, D816V, D816.

Changed Imatinib in Gastrointestinal Stromal Tumour with KIT : R2

Alterations changed: V654A, N655S, T670I, N680K, F681L, C809G, D816G, D816H, D816V, D816, D820G, D820E, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840NV654A, N655S, T670I, N680K, F681L, C809G, D816G, D816H, D816V, D820G, D820E, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840N.