History of database changes

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

05 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

04 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

01 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

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

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   (First curated: 2023-01-20)

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

08 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

05 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

04 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

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

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.. (First curated: 2020-05-04)

Changed Therapy in Cholangiocarcinoma with FGFR2 Fusion: 3

Therapy changed: LirafugratinibRLY-4008. (First curated: 2022-10-12)

Changed Therapy in Cholangiocarcinoma with FGFR2 Fusion, C382R, R678H, H167_N173del, C383R, W290C: 3

Therapy changed: LirafugratinibRLY-4008. (First curated: 2023-07-08)

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. (First curated: 2020-11-17)

Changed Therapy in Solid tumours with FGFR2 Fusion: 4

Therapy changed: LirafugratinibRLY-4008. (First curated: 2021-12-15)

Changed MRTX1133 with KRAS G12D: 4

Cancer type(s) changed: Pancreatic adenocarcinoma, Colorectal adenocarcinoma (First curated: 2022-12-07)

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.. (First curated: 2022-08-07)

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. (First curated: 2020-11-15)

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%. (First curated: 2020-07-30)

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.. (First curated: 2024-04-30)

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%. (First curated: 2020-07-30)

Changed Vismodegib in Medulloblastoma with SMO D473, E518: R2

Comments changed: Preclinical study. GDC-0449-resistant SMO mutants identified with D473H and E518 mutations. (First curated: 2021-02-28)

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.. (First curated: 2021-06-08)

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

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).. (First curated: 2024-09-09)

09 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

08 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 FCN-159 in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

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. References: 10.1200/JCO.2023.41.16_suppl.10023

Changed Selumetinib with NF1 Oncogenic mutations (germline): 1

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. (First curated: 2020-04-16)

Changed Mirdametinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

Comments changed: 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.NF106. Phase II trial. ORR 42%; CBR 95%.. (First curated: 2021-02-02)

07 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: 1

Tier changed: 12. (First curated: 2021-04-23)

Changed Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 1

Tier changed: 12. (First curated: 2023-12-16)

Changed Pembrolizumab in Endometrial cancer with Microsatellite Instability High: 1

Tier changed: 12. (First curated: 2022-01-17)

06 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

04 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: 1

Tier changed: 1B. (First curated: 2021-06-05)

03 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. (First curated: 2020-04-16)

02 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

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

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

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

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

08 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. (First curated: 2022-06-15)

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

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. (First curated: 2023-06-20)

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. (First curated: 2023-06-20)

Changed Trastuzumab deruxtecan in Pancreatic adenocarcinoma with ERBB2 Overexpression, Protein expression: R2

References changed: 37870536, 10.1200/JCO.2023.41.17_suppl.LBA3000. (First curated: 2023-06-20)

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. (First curated: 2024-07-15)

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:

04 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. (First curated: 2024-06-09)

Changed Dinaciclib + MK2206 in Ovarian cancer with CCNE1 Amplification: 4

(First curated: 2020-10-011/10/2020)

Changed SNS-032 in Ovarian cancer with CCNE1 Amplification: 4

(First curated: 2020-10-011/10/2020)

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. (First curated: 2020-04-16)

Changed Durvalumab in Endometrial cancer with Microsatellite Instability : R2

Alterations changed: Stable, NOT High. (First curated: 2023-07-14)

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

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. (First curated: 2024-05-14)

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

17 June, 2024 (Version: 20240617AU)

Changed NST-628 with BRAF Class II mutations, Class III mutations: 4

Cancer type(s) changed: Solid tumours (First curated: 2024-05-27)

09 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. (First curated: 2022-06-07)

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. (First curated: 2023-03-20)

Changed Therapy in Solid tumours with NTRK1 Fusion: 4

Therapy changed: TaletrectinibDS-6051b. (First curated: 2020-04-30)

Changed Therapy in Solid tumours with NTRK2 Fusion: 4

Therapy changed: TaletrectinibDS-6051b. (First curated: 2020-04-30)

Changed Therapy in Solid tumours with NTRK3 Fusion: 4

Therapy changed: TaletrectinibDS-6051b. (First curated: 2020-04-30)

Changed Therapy in Non-small cell lung cancer with ROS1 Fusions; G2032R: 4

Therapy changed: TaletrectinibDS-6051b. (First curated: 2020-04-25)

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