History of database changes

Saturday, 13 August 2022 (Version: 20220813AU) (Latest version)

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%).. (First curated: 2021-09-19)

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. (First curated: 2020-11-10)
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.. (First curated: 2020-05-06)
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. (First curated: 2021-06-07)

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. (First curated: 2020-04-16)
Changed Therapy in Colorectal cancer with NRAS Oncogenic mutations: R1
Therapy changed: Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + PanitumumabPanitumumab, Cetuximab, Cetuximab + Irinotecan. (First curated: 2020-04-16)

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.. (First curated: 2020-05-12)
Changed Crizotinib in Inflammatory myofibroblastic tumour with ALK Fusions, RANBP2-ALK Fusion: 2
Comments changed: Not TGA approved. FDA approved 14/7/2022.. (First curated: 2020-04-16)
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.. (First curated: 2021-06-05)

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. (First curated: 2020-04-27)
Changed Crizotinib in Non-small cell lung cancer with MET : 4
Alterations changed: D1028H (D1010H). (First curated: 2022-07-04)
Changed Crizotinib in Non-small cell lung cancer with MET : 4
Alterations changed: D1028N (D1010N). (First curated: 2022-07-04)
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. (First curated: 2020-05-15)
Changed Crizotinib in Non-small cell lung cancer with MET : 4
Alterations changed: Y1003S (Y1021S). (First curated: 2021-01-03)
Changed Crizotinib in Non-small cell lung cancer with MET : 4
Alterations changed: Y1021H (Y1003H). (First curated: 2021-01-03)
Changed Cabozantinib in Gastrointestinal stromal tumour with MET : 4
Alterations changed: Y1248H (Y1230H), D1246N (D1228N), K1262R (K1244R)Y1248H, D1246N, K1262R. (First curated: 2021-08-13)
Changed Crizotinib in Non-small cell lung cancer with MET : R2
Alterations changed: D1228N (D1246N). (First curated: 2021-01-03)
Changed Crizotinib in Triple-negative breast cancer with MET : R2
Alterations changed: D1228N (D1246N). (First curated: 2020-05-15)
Changed Capmatinib, Tepotinib, Savolitinib in Non-small cell lung cancer with MET : R2
Alterations changed: D1228N (D1246N), D1228 (D1246)D1228N, D1228. (First curated: 2020-05-31)
Changed Crizotinib in Non-small cell lung cancer with MET : R2
Alterations changed: D1246N (D1228N). (First curated: 2021-01-03)
Changed Crizotinib in Non-small cell lung cancer with MET : R2
Alterations changed: F1007fs (F1025fs). (First curated: 2021-01-03)
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. (First curated: 2021-01-03)
Changed Glesatinib in Non-small cell lung cancer with MET : R2
Alterations changed: H1094Y (H1112Y), L1195V (L1213V)H1094Y, L1195V. (First curated: 2020-05-31)
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. (First curated: 2020-05-15)
Changed Crizotinib in Non-small cell lung cancer with MET : R2
Alterations changed: Y1230C (Y1248C). (First curated: 2021-01-03)
Changed Crizotinib in Non-small cell lung cancer with MET : R2
Alterations changed: Y1230H (Y1248H). (First curated: 2021-01-03)
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. (First curated: 2021-01-03)

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 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.. (First curated: 2022-04-09)
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.. (First curated: 2022-04-09)
Changed Therapy in Colorectal cancer with BRAF V600E: R1
Therapy changed: Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab. (First curated: 2020-05-04)

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. (First curated: 2020-05-30)

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

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: 1
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. (First curated: 2020-11-10)
Changed Larotrectinib with NTRK2 Fusions, GNAQ-NTRK2 fusion, RBPMS-NTRK2 fusion, STRN-NTRK2 fusion, TRAF2-NTRK2 fusion: 1
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. (First curated: 2020-11-10)
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: 1
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. (First curated: 2020-11-10)

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: 2
Tier changed: 23. Comments changed: Not TGA approved. FDA approval for tumour agnostic indication 23/06/22. ROAR. BICR ORR 47%.. (First curated: 2020-09-21)
Changed Dabrafenib + Trametinib in Gliomas, High-grade gliomas, Low-grade gliomas with BRAF V600E: 2
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.. (First curated: 2021-12-07)
Changed Dabrafenib + Trametinib in Solid tumours except Colorectal cancer, melanoma, thyroid cancer with BRAF V600E: 2
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.. (First curated: 2020-12-30)
Changed Therapy in Non-small cell lung cancer with CEACAM5 Overexpression: 4
Therapy changed: Tusamitamab ravtansineSAR408701. (First curated: 2020-06-13)

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

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. (First curated: 2022-06-06)

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   (First curated: 2021-06-18)
Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification, Overexpression: 1B
Tier changed: 1B2. (First curated: 2021-09-20)
Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification; Overexpression: 1B
Tier changed: 1B2. (First curated: 2020-05-12)
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. (First curated: 2022-01-05)

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 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

Wednesday, 8 June 2022 (Version: 20220608AU)

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. (First curated: 2022-06-06)
Changed Nirogacestat in Adenoid cystic carcinoma with NOTCH1 R2327fs*: 3
References changed: 3499464410.1200/PO.21.00228. (First curated: 2021-11-04)
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. (First curated: 2021-09-20)
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.. (First curated: 2022-02-09)
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.. (First curated: 2022-02-09)
Changed Mirvetuximab soravtansine in Ovarian cancerOverexpression: 4
Biomarker changed: FOLR1. (First curated: 2020-06-13)
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.. (First curated: 2022-02-09)
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.. (First curated: 2022-02-09)
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.. (First curated: 2022-02-09)
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. (First curated: 2022-06-04)

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. (First curated: 2021-06-05)

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. (First curated: 2020-05-31)

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. (First curated: 2021-07-11)
Changed Mirvetuximab soravtansine + Bevacizumab in Ovarian cancerProtein expression: 3
Biomarker changed: FOLR1. (First curated: 2021-07-01)
Changed Cisplatin in Nonseminoma, Seminoma with Chromosome 3p25.3 copy number gain: R2
References changed: 35442716. (First curated: 2022-04-21)

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. (First curated: 2020-05-31)

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

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. (First curated: 2021-02-12)

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. (First curated: 2020-05-12)

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 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. (First curated: 2022-01-28)

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: 1B
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).. (First curated: 2020-05-12)
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. (First curated: 2020-05-15)

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.. (First curated: 2020-04-25)

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: 2
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.. (First curated: 2022-01-17)
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.. (First curated: 2021-06-21)
Changed Therapy in Prostate cancer with PSMA Protein expression: 3
Therapy changed: Lu-177 vipivotide tetraxetanLutetium-177-PSMA-617. (First curated: 2020-04-16)

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. (First curated: 2021-03-19)

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 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. (First curated: 2021-01-12)
Changed Trametinib in Pancreatic acinar cell carcinoma with RAF1 Fusion; GATM-RAF1 fusion: R2
References changed: 3510073110.1200/PO.19.00159. (First curated: 2021-01-12)

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. (First curated: 2022-03-04)