History of database changes

07 March, 2026 (Version: 20260307AU) (Latest version)

New Avelumab + Talazoparib in Ovarian cancer with BRCA1 Oncogenic mutations: 3: Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 63.6% in platinum-sensitive, BRCA1/2-altered OC (n=20, median PFS not reached, DOR not reached). Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials. References: 36394849
New Avelumab + Talazoparib in Ovarian cancer with BRCA2 Oncogenic mutations: 3: Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 63.6% in platinum-sensitive, BRCA1/2-altered OC (n=20, median PFS not reached, DOR not reached). Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials. References: 36394849
New Avelumab + Talazoparib in Breast cancer with ESR1+ERBB2+BRCA1 Oncogenic mutations: 3: Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 34.8% in HR-positive, ERBB2-negative, DDR-positive BC (n=23, median PFS 5.3 months, DOR 15.7 months)Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials. References: 36394849
New Avelumab + Talazoparib in Breast cancer with ESR1+ERBB2+BRCA2 Oncogenic mutations: 3: Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 34.8% in HR-positive, ERBB2-negative, DDR-positive BC (n=23, median PFS 5.3 months, DOR 15.7 months)Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials. References: 36394849

05 March, 2026 (Version: 20260305AU)

New Nivolumab + Ipilimumab, Nivolumab in Solid tumours with Tumour Mutational Burden High: 3: Phase 2. CheckMate 848. NCT03668119. N=201. Randomized open-label. Advanced or metastatic solid tumors with high tumor mutational burden (tTMB-H or bTMB-H). Refractory to standard therapies. Randomized 2:1 to nivolumab plus ipilimumab or nivolumab monotherapy. In tTMB-H patients, ORR was 38.6% with nivolumab plus ipilimumab versus 29.8% with nivolumab monotherapy. In bTMB-H patients, ORR was 22.5% with nivolumab plus ipilimumab versus 15.6% with nivolumab monotherapy. Early and durable responses observed with combination therapy. References: 39107131
New Sotorasib, RM-018, RMC-7977 in Solid tumours with KRAS H95L: 4: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Divarasib, RM-018, RMC-7977 in Solid tumours with KRAS M72I: 4: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib, RM-018, RMC-7977 in Solid tumours with KRAS Q99L: 4: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New RM-018, RMC-7977 in Solid tumours with KRAS R68S: 4: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New RM-018, RMC-7977 in Solid tumours with KRAS Y96D: 4: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with ARAF R544L: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with BRAF V600E, Fusion, K601E, E275D, G469A, G596C, L597R, L597Q: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with GNAS K216N: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with HRAS G13V: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with KRAS Amplification, G12D, G12V, Q61H, G13D, G12A, G12R, G12S, G12L, G12F, Q61L, V8L, G12W, A146P, A146T, H95R, Y96N, H95Q, Y96H, M72I, M72T, H95D, H95N: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Adagrasib, Divarasib in Solid tumours with KRAS H95L: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Adagrasib in Solid tumours with KRAS M72I: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Solid tumours with KRAS R68S: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Solid tumours with KRAS Y96D: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with MAP2K1 R47_E62delinsQ, Q56P, K57N, K57T, E102_I103del, E203K: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with NRAS Amplification, Q61K, Q61R, Q61L, Y96H, G13R, Q61H, A146V: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
New Sotorasib, Adagrasib, Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma with RAF1 K53T: R2: Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations. References: 39914665
Changed 9MW2821 in Solid Tumours, Urothelial carcinoma, Cervical Cancer, Oesophageal cancer, Triple-negative breast cancer with NECTIN4 Protein expression: 3: References changed: 40288679, 10.1200/JCO.2024.42.16_suppl.3013. (First curated: 2024-06-09)

04 March, 2026 (Version: 20260304AU)

New FOLFOXIRI + Panitumumab, 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: Phase 3 TRIPLETE study. NCT03231722. N=435. Upfront mFOLFOXIRI plus panitumumab significantly improved OS (41.1 months) compared with mFOLFOX/panitumumab (33.3 months) in RAS/BRAF wild-type mCRC. ORR was 78% (experimental) vs 75% (control). No differences in PFS (HR, 0.95), early tumor shrinkage, depth of response, and no residual tumor resection rate. References: 41505697
New Fuzuloparib + Apatinib in Breast cancer with BRCA1+ERBB2 BRCA1:Oncogenic mutations (germline) AND NOT ERBB2:Amplification AND NOT ERBB2:Overexpression: 2: Phase 3 FABULOUS trial. NCT04296370. N=203. Fuzuloparib with apatinib significantly improved PFS (11.0 months) compared to fuzuloparib alone (6.7 months) and chemotherapy (3.0 months) in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations. Fuzuloparib-apatinib HR 0.27, p<0.0001; fuzuloparib HR 0.49, p=0.0004. References: 41308673
New Fuzuloparib + Apatinib in Breast cancer with BRCA2+ERBB2 BRCA2:Oncogenic mutations (germline) AND NOT ERBB2:Amplification AND NOT ERBB2:Overexpression: 2: Phase 3 FABULOUS trial. NCT04296370. N=203. Fuzuloparib with apatinib significantly improved PFS (11.0 months) compared to fuzuloparib alone (6.7 months) and chemotherapy (3.0 months) in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations. Fuzuloparib-apatinib HR 0.27, p<0.0001; fuzuloparib HR 0.49, p=0.0004. References: 41308673
New Eribulin + Trastuzumab + Pertuzumab in Breast cancer with ERBB2 Amplification, Overexpression: 2: Phase 3 EMERALD trial. NCT03264547. N=446. Trastuzumab-pertuzumab plus eribulin noninferior to taxane in first-line HER2+ breast cancer. Median PFS 14.0 months versus 12.9 months (HR, 0.95 [95% CI, 0.76 to 1.19]). Median OS not reached versus 65.3 months in taxane group. References: 39787453
New Tucatinib + Trastuzumab + Pertuzumab in Breast cancer with ERBB2 Amplification, Overexpression: 2: Phase 3. HER2CLIMB-05. NCT05132582. N=654. Tucatinib plus trastuzumab and pertuzumab versus placebo plus trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer. Investigator-assessed PFS significantly improved with tucatinib (24.9 v 16.3 months). PFS benefit observed regardless of brain metastasis presence or hormone receptor status. OS data immature. References: 41369677
New Zanidatamab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Amplification; Overexpression: 2: Not TGA approved. FDA approved (accelerated). Phase 2 trial. NCT03929666. N=46. Zanidatamab plus chemotherapy showed a confirmed objective response rate of 76.2% with a median duration of response of 18.7 months in HER2-positive advanced gastro-oesophageal adenocarcinoma. Median PFS was 12.5 months and median OS was 36.5 months. References: 40473445
New Abemaciclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: Phase 3. postMONARCH. NCT05169567. N=368. Abemaciclib plus fulvestrant improved investigator-assessed PFS over placebo plus fulvestrant (HR 0.73; median 6.0 vs 5.3 months) in HR+, HER2- advanced breast cancer after CDK4/6i progression. BICR PFS HR 0.55. ORR 17% versus 7%. Consistent effect across ESR1 and PIK3CA mutation subgroups. References: 39693591
New Datopotamab deruxtecan in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: FDA approved. Phase 3. TROPION-Breast01. NCT05104866. N=732. HR+/HER2- metastatic breast cancer. Dato-DXd significantly improved PFS versus chemotherapy (HR, 0.63). OS trend favored Dato-DXd (HR, 0.84). Consistent PFS benefit across subgroups. References: 39265124
New Sotorasib + Panitumumab in Colorectal adenocarcinoma with KRAS G12C: 2: FDA approved. Phase 3 CodeBreaK 300. NCT05198934. N=160. Sotorasib 960 mg-panitumumab significantly prolonged PFS versus investigator's choice in chemorefractory KRAS G12C mCRC. Updated ORR 30.2% (95% CI, 18.3 to 44.3) for 960 mg, 7.5% for 240 mg, and 1.9% for investigator's choice. OS HR 0.70 (95% CI, 0.41 to 1.18) for 960 mg and 0.83 (95% CI, 0.49 to 1.39) for 240 mg versus investigator's choice. Median follow-up 13.6 months. Findings support sotorasib 960 mg-panitumumab as standard of care. References: 40215429
New Taletrectinib in Non-small cell lung cancer with ROS1 Fusions; G2032R mutation: 2: Phase 2. TRUST-I and TRUST-II. NCT04919811 and NCT04395677. N=273. ROS1+ NSCLC. Taletrectinib in TKI-naive patients (n=160): cORR 88.8%, IC-cORR 76.5%, median DOR 44.2 months, median PFS 45.6 months. In TKI-pretreated patients (n=113): cORR 55.8%, IC-cORR 65.6%, median DOR 16.6 months, median PFS 9.7 months. G2032R mutation cORR 61.5% (8 of 13). References: 40179330
New Patritumab deruxtecan in Non-small cell lung cancer with ALK Fusion: 3: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. References: 40554742
New Pivekimab sunirine in Blastic plasmacytoid dendritic cell neoplasm with CD123 Overexpression: 3: Phase 1/2. NCT03386513. Pivekimab sunirine (PVEK) showed a composite complete response rate of 75% in frontline de novo BPDCN patients, with median duration of response 10.6 months and median OS 16.6 months, and 53% proceeded to stem-cell transplant; in relapsed/refractory disease, CCR rate was 14%, with median duration 9.2 months and median OS 5.8 months. References: 41671533
New Camrelizumab + Famitinib, Camrelizumab in Cervical cancer with CD274 Protein expression: 3: Phase 2 randomized trial. NCT04680988. N=194. Camrelizumab plus famitinib versus camrelizumab in pretreated recurrent or metastatic cervical cancer. ORR per BICR significantly improved (41.0% vs 24.1%; P=.0181). Median PFS 8.1 vs 4.1 months. Median OS 20.2 vs 14.9 months. ORR benefit consistent across PD-L1 positive (44.6% vs 23.5%) and PD-L1 negative (35.0% vs 25.0%) subgroups, numerically higher in PD-L1 subgroup. Median DoR 16.0 months. References: 40561369
New Ifinatamab Deruxtecan in Small-cell lung cancer with CD276 Protein expression: 3: Phase 2 IDeate-Lung01 trial, NCT05280470, N=183, Ifinatamab Deruxtecan 12 mg/kg showed ORR of 48.2%, median DOR of 5.3 months, median PFS of 4.9 months, and 9-month OS estimate of 59.1%. Note no meaningful association was observed between B7-H3 expression by IHC and treatment response (Figure S1). References: 41086386
New CMG901 in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3: Phase 1 KYM901 trial. NCT04805307. CMG901, a Claudin 18.2-targeting antibody-drug conjugate, antitumour activity in patients with advanced gastric or gastro-oesophageal junction cancer with confirmed ORR of 28% (32/113). CLDN18.2 positivity was defined as membrane staining intensity of >= 2+ in >= 5% of tumour cells in the the dose expansion phase. References: 39788133
New Obrixtamig in Small-cell lung cancer, Extrapulmonary neuroendocrine carcinoma, Large cell neuroendocrine carcinoma of the lung with DLL3 Protein expression: 3: Phase I dose-escalation. NCT04429087. Obrixtamig (BI 764532). N=168. DLL3-positive SCLC, epNECs, or LCNEC-L. 72% received ≥2 lines prior therapy. Overall ORR 23% (95% CI, 17.4% to 30.2%). Median DoR 8.5 months (95% CI, 6.2 to not reached). 6-month DoR rate 70%. Regimens B2/B3 ORR 28%. Subgroup ORRs for SCLC 21%, epNECs 27%, and LCNEC-L 70%. Supports further exploration in heavily pretreated DLL3-positive tumors. References: 40706016
New Amivantamab + Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 3: Phase 1/1b. CHRYSALIS-2 trial. NCT04077463. N=105. Amivantamab plus lazertinib demonstrated antitumor activity in patients with atypical EGFR-mutated advanced NSCLC, with an ORR of 52%, mDoR of 14.1 months , and mPFS of 11.1 months. In treatment-naive patients, ORR was 57%, mPFS was 19.5 months, and mDoR was 20.7 months. In previously treated patients, ORR was 48%, mPFS was 7.8 months, and mDoR was 11.0 months. References: 41325571
New Sunvozertinib in Non-small cell lung cancer with EGFR Exon 20 insertion: 3: Phase II dose-randomized study. WU-KONG1B. NCT03974022. Sunvozertinib 200 mg or 300 mg. N=85, 89, 107 efficacy-evaluable patients across 200 mg-rand, 300 mg-rand, and 300 mg-all cohorts. Platinum-pretreated advanced NSCLC with EGFR exon20ins. Primary endpoint cORR was 45.9% (200 mg), 47.2% (300 mg-rand), and 45.8% (300 mg-all) per IRC. Null hypothesis rejected (P < .0001). DoR 13.8 months (300 mg) versus 11.1 months (200 mg). Subgroup cORR higher in baseline brain metastasis (52.4% v 28.6%) and prior amivantamab treatment (41.7% v 25%). Establishes efficacy for platinum-pretreated EGFR exon20ins NSCLC. References: 40923280
New Afatinib in Non-small cell lung cancer with EGFR G719X, L861Q, S768I, Exon 18 deletion, Exon 19 insertion, L747P, Oncogenic mutations and NOT Exon 20 insertion and NOT Exon 19 deletion and NOT L858R and NOT T790M: 3: Randomized open-label study. ACHILLES/TORG1834. jRCTs031180175. N=109. Treatment-naive nonsquamous NSCLC with uncommon EGFR mutations. Afatinib significantly improved median PFS over platinum-pemetrexed chemotherapy (10.6 vs 5.7 months; HR, 0.421; P = .0010). ORR was 61.4% for afatinib versus 47.1% for chemotherapy. Median DoR favored afatinib (10.6 vs 5.6 months; HR, 0.348). OS data immature. References: 40239133
New Patritumab deruxtecan in Non-small cell lung cancer with EGFR L861R, T751_I759delinsN, Oncogenic mutation AND NOT Exon 20 insertion: 3: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. References: 40554742
New Patritumab deruxtecan in Non-small cell lung cancer with ERBB2 A775_G776insYVMA, D769Y: 3: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. References: 40554742
New Zanidatamab + Palbociclib + Fulvestrant in Breast cancer with ERBB2+ESR1 ESR1:Protein expression AND ERBB2:Amplification, ESR1:Protein expression AND ERBB2:Overexpression: 3: Phase 2a study. NCT04224272. N=51. Zanidatamab plus palbociclib and fulvestrant showed promising antitumour activity with PFS at 6 months being 66.7% in heavily pretreated hormone receptor-positive, HER2-positive metastatic breast cancer patients. Most common adverse events were diarrhoea (80%) and neutropenia (51%). References: 40339592
New Ribociclib + Letrozole in Low-grade serous ovarian cancer with ESR1 Protein expression: 3: Phase 2 GOG 3026 trial. NCT03673124. N=49. Confirmed ORR was 30.6% with 1 complete and 14 partial responses. Median duration of response was 21.2 months. CBR was 84%. Median PFS was 14.5 months. Median OS was 44.5 months. ER not explicity required into the trial but >=95% of LGSOC are expected to have ER positivity. References: 41385758
New Camizestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3: Phase 2 SERENA-3 trial. N=132. Camizestrant reduced ER expression by approximately 65% for all doses. Greater reduction in Ki67 expression was seen after 12-15 days compared to 5-7 days. Maximal effects on ER and Ki67 expression were achieved with camizestrant 75 mg once daily. References: 41628308
New Erdafitinib, Erdafitinib + Cetrelimab in Urothelial carcinoma with FGFR3 S249C, R248C, Y373C, G370C, Fusions, FGFR3-TACC3 fusion: 3: Phase 2 NORSE trial. NCT03473743. N=87. Erdafitinib monotherapy had an ORR of 44.2% with median DOR of 9.7 months, PFS of 5.6 months, and OS of 16.2 months. Erdafitinib plus cetrelimab had an ORR of 54.5% with median DOR of 11.1 months, PFS of 11.0 months, and OS of 20.8 months. References: 41538748
New Quizartinib in Acute myeloid leukaemia with FLT3 NOT Internal tandem duplication: 3: Phase 2 QUIWI trial. NCT04107727. N=273. Quizartinib significantly improved EFS (20.4 vs 9.9 months) and OS (not reached vs 29.3 months) compared to placebo in patients with FLT3-ITD-negative AML, with 3-year OS rates of 60.8% vs 45.7%. References: 41082703, 41325561
New Azacitidine + Venetoclax + Revumenib in Acute myeloid leukaemia with KMT2A Rearrangement: 3: Phase 1. NCT03013998. N=43. Azacitidine, venetoclax, and revumenib in newly diagnosed AML aged 60+ with NPM1m or KMT2Ar. ORR 88.4% (NPM1m 85.3%, KMT2Ar 100%). Composite CR 81.4% (NPM1m 79.4%, KMT2Ar 88.9%). CR 67.4% (NPM1m 65%, KMT2Ar 78%). Median time to response 28 days. 100% MRD negative in 37 evaluated patients. High rates of CR and clinical activity observed. References: 40504618
New Divarasib in Non-small cell lung cancer with KRAS G12C: 3: Phase I. GO42144. NCT04449874. N=65. Single-agent divarasib in advanced KRAS G12C-positive NSCLC. Confirmed ORR 55.6% (95% CI, 42.5 to 68.1) in measurable disease (n=63). Median DOR 18.0 months (95% CI, 11.1 to 24.9). Median PFS 13.8 months (95% CI, 9.8 to 25.4) overall and 15.3 months (95% CI, 12.3 to 26.1) at 400-mg dose. 48% treated beyond 1 year. References: 40632992
New Onvansertib + FOLFIRI + Bevacizumab in Colorectal adenocarcinoma with KRAS Oncogenic mutations: 3: Phase II. NCT03829410. N=53. Onvansertib + FOLFIRI + bevacizumab in KRAS-mutant mCRC. ORR 26.4%. Median DOR 11.7 months. No prior bevacizumab subgroup ORR 76.9% vs 10.0% and median PFS 14.9 months vs 6.6 months. First-line evaluation planned (NCT06106308). References: 39475591, 39561313
New Patritumab deruxtecan in Non-small cell lung cancer with KRSA G12: 3: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. References: 40554742
New Azacitidine + Venetoclax + Revumenib in Acute myeloid leukaemia with NPM1 Oncogenic mutation: 3: Phase 1. NCT03013998. N=43. Azacitidine, venetoclax, and revumenib in newly diagnosed AML aged 60+ with NPM1m or KMT2Ar. ORR 88.4% (NPM1m 85.3%, KMT2Ar 100%). Composite CR 81.4% (NPM1m 79.4%, KMT2Ar 88.9%). CR 67.4% (NPM1m 65%, KMT2Ar 78%). Median time to response 28 days. 100% MRD negative in 37 evaluated patients. High rates of CR and clinical activity observed. References: 40504618
New Ziftomenib in Acute myeloid leukaemia with NPM1 Oncogenic mutation: 3: Phase II. KOMET-001. NCT04067336. N=92. Ziftomenib met primary endpoint CR/CRh rate 22% (95% CI, 14 to 32) in relapsed/refractory NPM1-mutated AML. ORR 33% (95% CI, 23 to 43). Median DOR 4.6 months (95% CI, 2.8 to 7.4). Median OS 6.6 months (95% CI, 3.6 to 8.6). 61% negative for measurable residual disease. Comparable CR/CRh regardless of prior venetoclax or comutations. References: 40997296
New Patritumab deruxtecan in Non-small cell lung cancer with NRAS Q61L: 3: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. References: 40554742
New Patritumab deruxtecan in Non-small cell lung cancer with RET Fusion: 3: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. References: 40554742
New Selpercatinib in Non-small cell lung cancer with RET KIF5B-RET fusion, CCDC6-RET fusion, NCOA4-RET fusion, Fusions: 3: Phase I/II. LIBRETTO-001. NCT03157128. N=316 (247 pretreated, 69 naive). Selpercatinib in RET fusion-positive NSCLC. ORR 62% pretreated, 83% naive. Median DoR 31.6 months pretreated, 20.3 months naive. Median PFS 26.2 months pretreated, 22.0 months naive. Median OS 47.6 months pretreated, not reached naive. 3-year OS 57% pretreated, 66% naive. CNS-ORR 85%, CNS-PFS 11.0 months. References: 39983053
New Patritumab deruxtecan in Non-small cell lung cancer with ROS1 Fusion: 3: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. References: 40554742
New Adavosertib in Uterine serous carcinoma with CCNE1 Amplification, Protein expression: 4: Phase IIb, ADAGIO. NCT04590248. N=104. Adavosertib demonstrated an ORR by BICR of 26.0% in recurrent/persistent uterine serous carcinoma previously treated with platinum-based chemotherapy. Median DoR was 4.7 months. Median PFS was 2.8 months. Biomarker analysis identified no single predictive alteration, although a trend was observed for CCNE1 amplification or high cyclin E1 protein expression. References: 40262070
New FOR46 in Prostate cancer with CD46 Overexpression: 4: Phase I. FOR46 (FG-3246). NCT03575819. N=56. In patients with progressive mCRPC after ≥one androgen signaling inhibitors, median radiographic PFS was 8.7 months in efficacy evaluable subset (n=40). Confirmed ORR was 20% (5/25 RECIST-evaluable). PSA50 response was 36% (14/39). Median DOR was 7.5 months. Responders associated with higher on-treatment circulating effector CD8+ T cells. Note, Response was not clearly associated with CD46 expression despite mechanism of action. References: 40138611
New Patritumab deruxtecan in Non-small cell lung cancer with ERBB2 Amplification: 4: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. Note 1 case of ERBB2 amplification had best response of PD. References: 40554742
New Cetuximab, Panitumumab in Colorectal adenocarcinoma with KRAS+NRAS+Consensus molecular subtype Consensus molecular subtype:CMS4 and NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 4: IPD Meta-Analysis. FIRE1, FIRE3, XELAVIRI, PanaMa, TRIBE2. N=790. RAS WT mCRC. CMS4 anti-EGFR vs anti-VEGF PFS HR 0.67 (P = .03), OS HR 0.49 (P < .001). CMS2/CMS4 vs CMS1 ORR OR 1.668/1.369, PFS HR 0.64/0.67, OS HR 0.59/0.67. Interaction test PFS/OS P < .001. CMS4 potential biomarker for anti-EGFR efficacy. References: 41252656
New Patritumab deruxtecan in Non-small cell lung cancer with MET Amplification: 4: Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. Note 1 case of MET amplification had best response of PD. References: 40554742
New Tislelizumab in Oesophageal squamous cell carcinoma with NOTCH1 Oncogenic mutations: 4: Biomarker analysis. Phase 3. RATIONALE-302. NCT03430843. In advanced/metastatic ESCC with NOTCH1 mutation, tislelizumab versus chemotherapy showed longer OS (18.4 months vs 5.3 months; HR, 0.35). IFN-I signatures positively associated with OS benefit, B-cell and neutrophil signatures predicted unfavorable OS.'. References: 40179324
New Atezolizumab + Bevacizumab + Cisplatin + Gemcitabine in Biliary tract cancer with VEGFA High gene expression: 4: Phase 2. IMbrave151. NCT04677504. N=162. BTCs respond poorly to PD-1/PD-L1 inhibitors. Atezolizumab (anti-PD-L1) plus bevacizumab plus cisplatin and gemcitabine versus atezolizumab plus placebo plus cisplatin and gemcitabine in untreated advanced BTC. Median PFS 8.3 months versus 7.9 months (HR, 0.67). Median OS 14.9 versus 14.6 months (HR, 0.97). High VEGFA gene expression associated with improved PFS (HR, 0.44). References: 39423355
New Ipilimumab + Nivolumab in Glioblastoma with MGMT Unmethylated: R2: Phase II/III. NRG Oncology BN007. NCT04396860. N=159. Ipilimumab and nivolumab did not improve PFS over temozolomide (7.7 versus 8.5 months, HR 1.47) or OS (median approximately 13 months each, HR 0.95) in newly diagnosed MGMT-unmethylated glioblastoma. Accrual closed permanently. References: 40779733
Changed Encorafenib + Binimetinib in Non-small cell lung cancer with BRAF V600E: 2: Comments changed: Not TGA approved. FDA approved. Phase 2, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer. NCT03148795. PHAROS. N=98. ORR was 75% (treatment naive) and 46% (previously treated). DCR after 24 weeks was 64% in treatment-naïve and 41% in previously treated patients. Median PFS was NE in treatment-naïve and 9.3 months in previously treated patients. Median OS 47.6 months in treatment-naive patients; 4-year OS probability 49%. Median OS 22.7 months in previously treated patients; 4-year OS probability 31%. Median duration of treatment 16.3 months (naive) and 5.5 months (treated).. References changed: 37270692, 41109959. (First curated: 2023-10-17)
Changed Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 2: Comments changed: 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. Note, Rucaparib did not improve OS over chemotherapy (19.4 versus 25.4 months) in BRCA1/2-mutated relapsed ovarian cancer. 69% of patients in chemotherapy group crossed over to receive rucaparib.. References changed: 35298906, 39914419. (First curated: 2022-04-09)
Changed Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 2: Comments changed: Not TGA approved. NCT02855944. 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. Note, Rucaparib did not improve OS over chemotherapy (19.4 versus 25.4 months) in BRCA1/2-mutated relapsed ovarian cancer. 69% of patients in chemotherapy group crossed over to receive rucaparib.Not TGA approved. NCT02855944. Phase 3 ARIEL4 trial. NCT02855944. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5.7 months) in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation.. References changed: 35298906, 39914419. (First curated: 2022-04-09)
Changed Zipalertinib in Non-small cell lung cancer with EGFR Exon 20 insertion: 2: References changed: 40450572, 10.1200/JCO-25-00763, 10.1200/JCO.2025.43.16_suppl.8503. (First curated: 2025-06-01)
Changed Vorasidenib in Low-grade gliomas with IDH1 Oncogenic mutation: 2: Comments changed: Phase 3. NCT04164901. INDIGO. N=331. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26).. References changed: 37272516, 41175888. (First curated: 2023-06-05)
Changed Atezolizumab + Carboplatin + Paclitaxel in Endometrial cancer with Mismatch repair Deficient: 2: References changed: 39102832. (First curated: 2025-07-30)
Changed Zongertinib in Non-small cell lung cancer with ERBB2 Tyrosine kinase domain mutation, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, L755P, G776V: 3: References changed: 40293180. (First curated: 2025-05-24)
Changed Zongertinib in Non-small cell lung cancer with ERBB2 Extracellular domain mutation, Transmembrane domain, Intracellular domain, S310F, S310Y, D277Y, S113F, V659E, G660D, P1199S: 4: References changed: 40293180. (First curated: 2025-05-24)

03 March, 2026 (Version: 20260303AU)

New Sacituzumab Govitecan + Pembrolizumab in Triple-negative breast cancer with CD274+ESR1+ERBB2 NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and NOT CD274:protein expression: 2: Phase 3 ASCENT-04/KEYNOTE-D19. NCT05382286. N=443. Sacituzumab Govitecan + Pembrolizumab significantly prolonged PFS over chemotherapy + Pembrolizumab (11.2 vs 7.8 months) in previously untreated PD-L1–positive advanced TNBC. Objective response rate was 60% vs 53%; median DOR 16.5 vs 9.2 months. References: 41564397
New Trastuzumab + Pertuzumab + Palbociclib + Letrozole, Trastuzumab + Pertuzumab + Palbociclib + Anastrozole, Trastuzumab + Pertuzumab + Palbociclib + Fulvestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression AND ERBB2:Amplification, ESR1:Protein expression AND ERBB2:Overexpression: 2: Phase 3. PATINA. NCT02947685. N=518. Addition of palbociclib to maintenance HER2-targeted and endocrine therapies significantly improved progression-free survival compared to standard therapy (median 44.3 vs 29.1 months). References: 41604639
New Tarlatamab in Small-cell lung cancer with DLL3 Protein expression: 2: Phase 3. DeLLphi-304 trial. NCT05740566. N=509. Tarlatamab significantly improved OS (13.6 vs 8.3 months) and PFS compared to chemotherapy (topotecan, lurbinectedin, or amrubicin) in patients with small-cell lung cancer after platinum-based chemotherapy. Note DLL3 expression is not required for entry into the trial. Treatment outcome was not evaluated against DLL3 expression. References: 40454646
New Camizestrant + Palbociclib, Camizestrant + Ribociclib, Camizestrant + Abemaciclib in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and ESR1:Oncogenic mutations, ESR1:D538G, ESR1:Y537S, ESR1:Y537N: 2: Not TGA approved. Phase 3 SERENA-6 trial, NCT04964934, N=315, ER-positive, HER2-negative advanced breast cancer, ESR1 mutation detected in ctDNA, patients switched to camizestrant (75mg daily) or continued aromatase inhibitor, both with CDK4/6 inhibitor, median PFS 16.0 months (camizestrant) vs 9.2 months (aromatase inhibitor). References: 40454637
New Trastuzumab deruxtecan + Pertuzumab in Breast cancer with ERBB2 Amplification, Overexpression: 2: Phase 3. DESTINY-Breast09 trial. NCT04784715. N=770. Trastuzumab deruxtecan plus pertuzumab significantly improved PFS (40.7 months) compared to taxane, trastuzumab, and pertuzumab (THP) (26.9 months) as first-line treatment for HER2-positive metastatic breast cancer. ORR was 85.1% with trastuzumab deruxtecan plus pertuzumab and 78.6% with THP. References: 41160818
New Trastuzumab deruxtecan in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Amplification, Overexpression: 2: Phase 3. DESTINY-Gastric04 trial. NCT04704934. N=494. Trastuzumab deruxtecan significantly improved OS (14.7 vs 11.4 months) and PFS over ramucirumab plus paclitaxel in HER2-positive metastatic gastric cancer, ORR 44.3% vs 29.1%. References: 40454632
New Zongertinib in Non-small cell lung cancer with ERBB2 Oncogenic mutations, Tyrosine kinase domain mutation, A775_G776insYVMA, P780_Y781insGSP, G776delinsVC, L755P, G776V, S310F, V659E: 3: Phase 1a-1b trial. NCT04886804. Zongertinib showed clinical benefit in patients with previously treated HER2-mutant NSCLC, with ORR of 71% (Cohort 1, 120mg dose), 48% (Cohort 5), and 30% (Cohort 3); Median PFS was 12.4 months (Cohort 1). References: 40293180
New Zongertinib in Non-small cell lung cancer with ERBB2 Extracellular domain mutation, S310Y, D277Y, S113F, Transmembrane domain mutations, G660D, Intracellular domain mutations, P1199S: 4: Phase 1a-1b trial. NCT04886804. Zongertinib showed clinical benefit in patients with previously treated HER2-mutant NSCLC. ORR was 30% (Cohort 3) with variable responses seen in selected extracellular, transmembrane, and intracellular domain mutations. References: 40293180
New Vepdegestrant in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and ESR1:Oncogenic mutations: 2: Phase 3 VERITAC-2 trial, NCT05654623, N=624, Vepdegestrant, a PROTAC ER degrader, significantly improved PFS over fulvestrant in ER-positive, HER2-negative advanced breast cancer patients with ESR1 mutations (5.0 vs 2.1 months, HR 0.58), but not in the overall population (3.8 vs 3.6 months, HR 0.83). References: 40454645
New Sacituzumab govitecan in Triple-negative breast cancer with ESR1+ERBB2 NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: Phase 3 ASCENT-03 trial, NCT05382299, N=558, Sacituzumab govitecan significantly improved PFS (9.7 months vs 6.9 months) over chemotherapy in patients with untreated advanced triple-negative breast cancer not eligible for PD-1/PD-L1 inhibitors, with similar ORR (48% vs 46%) and higher median duration of response (12.2 vs 7.2 months). References: 41124233
New Sevabertinib in Non-small cell lung cancer with ERBB2 Exon 20 insertions, A775_G776insYVMA, Oncogenic mutations,: 2: Phase 1-2 SOHO-01 trial, NCT05099172, N=209, Sevabertinib showed antitumor activity in HER2-mutant NSCLC patients with ORR of 64% (Cohort D), 38% (Cohort E), and 71% (Cohort F), with median PFS of 8.3 months, 5.5 months. References: 41104928
New Vebreltinib in Non-small cell lung cancer with MET Amplification: 3: Phase 2 KUNPENG trial. NCT04258033. N=86. Vebreltinib showed antitumour activity in patients with MET amplification-driven NSCLC, achieving an ORR of 48.8% (42/86) with a median follow-up of 18.6 months. MET amplification was determined by FISH with a gene copy number (GCN) >= 6 copies. No EGFR mutations, ALK fusion, ROS1 rearrangements, or KRAS mutations. References: 41365311
New Trastuzumab rezetecan in Non-small cell lung cancer with ERBB2 Exon 20 insertions, A775_G776insYVMA, G776delinsVC, P780_Y781insGSP, G776delinsLC: 3: Phase 2 HORIZON-Lung trial. NCT04818333. N=94. Trastuzumab rezetecan showed significant activity with an ORR of 73% in patients with advanced HER2-mutant NSCLC. References: 40020696
Changed Sacituzumab Govitecan in Triple-negative breast cancer with ESR1+ERBB2 : 1: Alterations changed: NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpressionNOT ESR1:protein expression and NOT ERBB2:amplified. (First curated: 2020-05-01)
Changed Amivantamab + Carboplatin + Pemetrexed, Amivantamab + Carboplatin + Pemetrexed + Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 1B: Comments changed: Phase 3. NCT04988295. MARIPOSA-2: Amivantamab and chemotherapy with or without lazertinib prolonged PFS for EGFR-mutant advanced NSCLC patients after progression on osimeterinib, versus chemotherapy alone (median PFS by investigator, 8.3, 8.3, and 4.2 months). ORR was higher (64% and 63% vs 36%). OS for amivantamab-lazertinib was significantly improved (HR 0.75, 3-year OS 60% vs 51%), with increased grade 3 or higher adverse events (80% vs 52%).. References changed: 37879444, 40923797. (First curated: 2024-05-19)
Changed Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 1B: Comments changed: Phase 3 FLAURA2 trial. NCT04035486. N=557. Combination of osimertinib with pemetrexed and a platinum agent led to significantly longer PFS over osimertinib monotherapy (19.3 v 11.2 months). ORR was similar between arms at 80% (osimertinib) and 84% (combination). Osimertinib plus chemotherapy significantly improved OS (47.5 months) compared to osimertinib monotherapy (37.6 months) in EGFR-mutated advanced NSCLC, with a HR of 0.77.. References changed: 37937763, 41104938. (First curated: 2023-11-09)
Changed Therapy in Colorectal adenocarcinoma with BRAF V600E: 2: Therapy changed: Encorafenib + Cetuximab + FOLFOXEncorafenib + Cetuximab + mFOLFOX6. Comments changed: TGA approved. PBS reimbursed. Phase 3 BREAKWATER trial. NCT04607421. Patients with untreated BRAF V600E-mutated metastatic colorectal cancer. EC+mFOLFOX6 showed significantly longer PFS (12.8 vs 7.1 months) and OS (30.3 vs 15.1 months) compared to standard care. Updated 2025-05-31.Not TGA approved. FDA approved. Phase 3 BREAKWATER trial (NCT04607421, N=637) demonstrated that encorafenib + cetuximab + mFOLFOX6 significantly improved outcomes compared to standard of care in previously untreated BRAF V600E-mutant metastatic colorectal cancer: ORR (60.9% vs 40.0%), median duration of response (13.9 vs 11.1 months), PFS (12.8 vs 7.1 months), and OS (30.3 vs 15.1 months). Updated 2025-05-31.. References changed: 40444708, 39863775, 10.1200/JCO.2025.43.16_suppl.LBA3500. (First curated: 2025-03-22)
Changed Sacituzumab tirumotecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 2: Comments changed: Phase 3. OptiTROP-Lung04 trial. (NCT05870319). N=376. 1:1 to sac-TMT versus pemetrexed + platinum chemotherapy in EGFR-mutated, EGFR-TKI-Resistant NSCLC with progression on EGFR-TKIs. Sac-TMT demonstrated significantly longer PFS (8.3 vs 4.3 months) and improved 18-month OS (65.8% vs 48.0%) compared to platinum-based chemotherapy.Phase 3 OptiTROP-Lung04 trial. NCT05870319. N=376. Sacituzumab tirumotecan (Sac-TMT) significantly improved PFS (8.3 vs 4.3 months) and OS (not reached vs 17.4 months) compared to platinum-based chemotherapy in EGFR-mutated NSCLC following progression on EGFR-TKIs.. References changed: 41124220, ESMO25.LBA5. (First curated: 2025-10-19)
Changed Disitamab vedotin + Toripalimab in Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 2: Comments changed: Phase 3. RC48-C016 trial. NCT05302284. N=484. Disitamab vedotin + toripalimab significantly improved PFS (13.1 vs 6.5 months), OS (31.5 vs 16.9 months), and ORR (76.1% vs 50.2%) over chemotherapy in patients with untreated HER2-expressing locally advanced or metastatic urothelial carcinoma.Phase 3 RC48-C016 trial. NCT05302284. N=484. Disitamab vedotin + toripalimab significantly improved PFS (13.1 vs 6.5 months) and OS (31.5 vs 16.9 months) over chemotherapy in patients with HER2-expressing locally advanced or metastatic urothelial carcinoma.. References changed: 41124210, ESMO25.LBA7. (First curated: 2025-10-19)
Changed Therapy in Breast cancer with ESR1+ERBB2+PIK3CA ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and PIK3CA:Oncogenic mutations: 2: Therapy changed: Inavolisib + Palbociclib + Fulvestrant. Comments changed: 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. OS improved (34.0 months vs 27.0 months).. References changed: 40454641, 10.1200/JCO.2024.42.16_suppl.1003. (First curated: 2024-10-13)
Changed Sacituzumab tirumotecan in Triple-negative breast cancer with ESR1+ERBB2 : 4: Alterations changed: NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpressionNOT ESR1:protein expression and NOT ERBB2:amplified, NOT ESR1:protein expression and NOT ERBB2:overexpression. (First curated: 2024-06-02)
Changed Rezatapopt with TP53 Y220C: 3: Cancer type(s) changed: Ovarian cancer, Solid tumours Tier changed: 34. Comments changed: Phase 1. PYNNACLE. NCT04585750. N=77. Across all dose groups, rezatapopt established. Overall response rate 20% (30% in KRAS wild-type tumors at ≥1150 mg), including confirmed responses in ovarian and breast cancers; all responders harbored TP53 Y220C and wild-type KRAS.PC14586 restored tumor suppressor function via conformational correction and DNA binding, supported by biochemical, structural, transcriptomic, and functional analyses, with potent antitumor activity in preclinical models as monotherapy and combined with immunotherapy.. (First curated: 2026-02-24)

24 February, 2026 (Version: 20260224AU)

New Rezatapopt in Solid tumours with TP53 Y220C: 4: PC14586 restored tumor suppressor function via conformational correction and DNA binding, supported by biochemical, structural, transcriptomic, and functional analyses, with potent antitumor activity in preclinical models as monotherapy and combined with immunotherapy. References: 39945593
New Cetuximab in Colorectal adenocarcinoma with KRAS Amplification: R2: Retrospective analysis. COH cohort and Flatiron cohorts. N=15. Wild-type RAS amplification in mCRC had median TTD 2.5 (COH) and 4.7 (CGDB) months vs 7.6 months in RAS wild-type, similar magnitude to EGFRmAb as RAS mutations. OS 11.4 vs 13.7 months. References: 33465286

06 February, 2026 (Version: 20260206AU)

New Olaparib in Solid Tumours with BRCA1 Oncogenic mutations: 3: Phase 2. Belgian Precision trial. BRCA1/2-mutated advanced cancers. N=27 (BRCA1) and 27 (BRCA2). ORR 11% (27 BRCA1: 3 PRs including pancreatic, gallbladder) and 21% (27 BRCA2: 5 PRs in pancreatic, parathyroid, and 1 CR in colon). Median PFS ≥14 months (5-34+ months in responders). CBR 63% (BRCA1) and 46% (BRCA2). References: 37852034
New Olaparib in Solid Tumours with BRCA2 Oncogenic mutations: 3: Phase 2. Belgian Precision trial. BRCA1/2-mutated advanced cancers. N=27 (BRCA1) and 27 (BRCA2). ORR 11% (27 BRCA1: 3 PRs including pancreatic, gallbladder) and 21% (27 BRCA2: 5 PRs in pancreatic, parathyroid, and 1 CR in colon). Median PFS ≥14 months (5-34+ months in responders). CBR 63% (BRCA1) and 46% (BRCA2). References: 37852034
New Olaparib in Solid Tumours with ATM Oncogenic mutations: R2: Phase 2. Belgian Precision. No clinical activity observed in ATM (n=13) or CHEK2 (n=14) cohorts. References: 37852034
New Olaparib in Solid Tumours with CHEK2 Oncogenic mutations: R2: Phase 2. Belgian Precision. No clinical activity observed in ATM (n=13) or CHEK2 (n=14) cohorts. References: 37852034

03 February, 2026 (Version: 20260203AU)

New Talazoparib in Hepatocellular carcinoma with BRCA1 Oncogenic mutations: 3: Phase 2 TAPUR Study. N=28. Talazoparib demonstrated antitumor activity in patients with BRCA1/2-mutated solid tumors, with a DCR of 57% and ORR of 36%, including responses in tumor types not currently approved for PARP inhibitors. References: 38865672
New Talazoparib in Prostate cancer, Cutaneous squamous cell carcinoma, Pancreatic adenocarcinoma, Gastric cancer, Oesophageal adenocarcinoma, Mesothelioma, Non-small cell lung cancer, Ovarian cancer, Endometrial cancer with BRCA2 Oncogenic mutations: 3: Phase 2 TAPUR Study. N=28. Talazoparib demonstrated antitumor activity in patients with BRCA1/2-mutated solid tumors, with a DCR of 57% and ORR of 36%, including responses in tumor types not currently approved for PARP inhibitors. References: 38865672

02 February, 2026 (Version: 20260202AU)

New PARP inhibitor in Prostate cancer, Ovarian cancer with Homologous Recombination Deficiency Score High: 4: Pan-cancer analysis of 260,333 samples identified 10 copy-number signatures associated with diverse processes, and a novel HRDsig that outperformed gLOH in predicting BRCAness. The PARPi benefit in was seen in clinicogenomic ovarian and prostate cancers. References: 37769224
New Olaparib in Chondrosarcoma, Solid tumours with IDH1 Oncogenic mutation: R2: Phase 2 study. NCT03212274. N=26. Olaparib did not demonstrate activity in IDH-mutant chondrosarcomas and other solid tumors with ORR 0%, median PFS of 2 months, and median OS of 7.5 months. References: 10.1200/JCO.2025.43.16_suppl.3087
New Olaparib in Chondrosarcoma, Solid tumours with IDH2 Oncogenic mutation: R2: Phase 2 study. NCT03212274. N=26. Olaparib did not demonstrate activity in IDH-mutant chondrosarcomas and other solid tumors with ORR 0%, median PFS of 2 months, and median OS of 7.5 months. References: 10.1200/JCO.2025.43.16_suppl.3087

19 January, 2026 (Version: 20260119AU)

Changed Capmatinib in Non-small cell lung cancer with MET : 4: Alterations changed: CD47-MET fusionCD74-MET fusion. (First curated: 2025-02-05)

15 December, 2025 (Version: 20251215AU)

New Sacituzumab tirumotecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 2: Phase 3 OptiTROP-Lung04 trial. NCT05870319. N=376. Sacituzumab tirumotecan (Sac-TMT) significantly improved PFS (8.3 vs 4.3 months) and OS (not reached vs 17.4 months) compared to platinum-based chemotherapy in EGFR-mutated NSCLC following progression on EGFR-TKIs. References: ESMO25.LBA5
New Disitamab vedotin + Toripalimab in Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 2: Phase 3 RC48-C016 trial. NCT05302284. N=484. Disitamab vedotin + toripalimab significantly improved PFS (13.1 vs 6.5 months) and OS (31.5 vs 16.9 months) over chemotherapy in patients with HER2-expressing locally advanced or metastatic urothelial carcinoma. References: ESMO25.LBA7
New Giredestrant + Everolimus in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: Phase 3 evERA BC trial. NCT05306340. N=373. Giredestrant + everolimus significantly improved PFS over SOC ET + everolimus (8.8 vs 5.5 months) in ER+, HER2- advanced breast cancer patients previously treated with a CDK4/6 inhibitor. References: ESMO25.LBA16
New Gedatolisib + Fulvestrant + Palbociclib, Gedatolisib + Fulvestrant, in Breast cancer with ERBB2+ESR1+PIK3CA PIK3CA:oncogenic mutations + ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: Phase 3 VIKTORIA-1 trial. NCT055001886. N=392. Gedatolisib + fulvestrant with or without palbociclib significantly improved PFS (9.3 vs 2.0 months)in HR+/HER2-/PIK3CA WT advanced breast cancer patients. ORR was 32% (triplet), 28.3% (doublet), and 1% (fulvestrant). References: ESMO25.LBA17
New Sacituzumab tirumotecan in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: Phase 3 OptiTROP-Breast02 study. NCT06081959. N=399. Sacituzumab tirumotecan significantly improved PFS over investigator's choice of chemotherapy (8.3 vs 4.1 months) with a manageable safety profile in patients with previously treated HR+/HER2- breast cancer. References: ESMO25.LBA23
New HRS-7058 in Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal adenocarcinoma, Solid tumour with KRAS G12C: 3: Phase 1 trial. NCT06383871. N=81. HRS-7058, a KRAS G12C inhibitor, showed promising antitumor activity with ORR of 48% and DCR of 94% in KRAS G12Ci-naive NSCLC. 3/4 patients with PDAC had tumour response. References: ESMO25.914O
New HRS-4642 in Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal adenocarcinoma, Solid tumour with KRAS G12D: 3: Phase 1 trial. N=84. HRS-4642, a KRAS G12D inhibitor, showed activity in NSCLC (ORR 24%, mPFS 5.6 months) and PDAC (ORR 21%, mPFS 4.1 months). References: ESMO25.915O
New INCB161734 in Solid Tumours, Non-small cell lung cancer, Pancreatic adenocarcinoma, Colorectal adenocarcinoma, Ovarian cancer, Solid tumour with KRAS G12D: 3: Phase 1. NCT06179160. N=36. INCB161734, a KRAS G12D inhibitor showed promising efficacy in 36 patients with advanced or metastatic solid tumors, with ORR of 30%, and DCR of 85% achieving disease control at doses ≥600 mg qd (PDAC 34%). References: ESMO25.916O
New Telisotuzumab adizuteca in Solid tumours with MET Amplification: 3: Phase 1 study. NCT05029882. N=100. Temab-A monotherapy showed activities in patients with MET-amplified advanced solid tumors, with a confirmed ORR of 46% and median PFS of 9.5 months across all dose levels and tumor types, including NSCLC (69%) and GEA (71%). References: ESMO25.918O
New DS-3939 in Solid tumours with MUC1 Protein expression: 3: Phase 1/2 FIH study NCT05875168. N=47. DS-3939, a tumour associated-MUC1-directed ADC, showed early signal of clinical activity in pretreated patients with various solid tumors, with 10 confirmed partial responses observed across NSCLC, OC, and BC. References: ESMO25.917O
New SNV1521 in Breast cancer with BRCA2 Oncogenic mutations (germline): 4: Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities. References: ESMO25.923MO
New AMT-116 in Solid tumours with CD44 Protein expression: 4: Phase 1/2 trials (NCT05725291; NCT06782334) of AMT-116, an anti-CD44v9 antibody-drug conjugate, showed manageable safety profile and promising antitumor activity across various solid tumors, with an ORR of 30% in EGFR wild-type NSCLC patients. References: ESMO25.922MO
New SNV1521 in Pancreatic adenocarcinoma with PALB2 Oncogenic mutations (germline): 4: Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities. References: ESMO25.923MO
New SNV1521 in Ovarian cancer with RAD51D Oncogenic mutations (germline): 4: Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities. References: ESMO25.923MO
New Cetuximab, Panitumumab in Colorectal adenocarcinoma with KRAS Amplification: R2: Case report. References: 28178681
New Cetuximab, Panitumumab, FOLFIRI + Cetuximab, Irinotecan + Cetuximab, FOLFOX + Panitumumab in Colorectal adenocarcinoma with NRAS Amplification: R2: Case report. References: 28178681

18 October, 2025 (Version: 20251018AU)

New Sevabertinib in Non-small cell lung cancer with ERBB2 Exon 20 insertions, A775_G776insYVMA, Tyrosine kinase domain mutations: 3: Phase 1/2. SOHO-01. NCT05099172. N=209. Three cohorts: D (previously treated without HER2-targeted therapy) had ORR 64%, median duration 9.2 months, PFS 8.3 months; E (previously received HER2 ADCs) ORR 38% with DOR duration 8.5 months, PFS 5.5 months; F (untreated) ORR 71% , with DOR 11.0 months, PFS immature. References: 10.1056/NEJMoa2511065
New Zongertinib in Non-small cell lung cancer with ERBB2 Exon 20 insertions, A775_G776insYVMA, Tyrosine kinase domain mutations: 3: Phase Ib. Beamion LUNG 1. NCT04886804. N=74. First-line zongertinib in treatment-naïve advanced HER2-mutant NSCLC showed ORR 77%, DOR 80%, PFS at 6 months 79%. References: ESMO25.LBA74
New MK-1084 in Non-small cell lung cancer, Colorectal cancer with KRAS G12C: 3: Phase I KANDLELIT-001 trial. NCT05067283. N=123. ORR 38% (CRC), 38% (NSCLC), 34% (others). Median PFS 6.2 (CRC), 8.3 (NSCLC), 5.7 mo. References: ESMO25.926MO
New Divarasib in Solid tumour except Colorectal adenocarcinoma, Non-small cell lung cancer, Pancreatic adenocarcinoma, Cholangiocarcinoma with KRAS G12C: 3: Phase 1. GO42144 (NCT04449874) and JO44179 (jRCT2031220195). N=32. Divarasib showed ORR of 34% (11/32) in KRAS G12C-positive non-NSCLC, non-CRC tumors (pancreatic: 27%, median PFS 7.1 mo; cholangiocarcinoma: 25%, median PFS 7.2 mo). Common TRAEs: diarrhea, nausea, anemia; no Grade 4-5 events. Updated TAPISTRY data (N=47) pending. Cholangiocarcinoma 23% (3/13); Pancreatic adenocarcinoma (31%). Other solid tumour (47%). References: ESMO25.927MO
New HRO761 in Colorectal adenocarcinoma with Microsatellite Instability High: 4: Phase I/Ib. HRO761. NCT05838768. N=47 (19 CRC). ORR 8.6% (10.5% in CRC), DCR 68.6% (84.2% in CRC), median PFS 5.6 months; 9-mo PFS rate 68.6% (95% CI 30.5–88.7) at 200 mg daily. ctDNA clearance observed in 6/14 pts with detectable baseline ctDNA, median treatment duration 9.3 months in responders. References: ESMO25.925MO

28 September, 2025 (Version: 20250928AU)

Changed Dabrafenib + Trametinib in Non-small cell lung cancer with BRAF V600E: 1: Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed. Phase 2 trial. NCT01336634. N=36. Dabrafenib + trametinib showed an ORR of 64% (23/36) with a median follow-up of 15.9 months in previously untreated BRAFV600E-mutant metastatic NSCLC.TGA approved. Not PBS reimbursed. Phase 2 trial. NCT01336634. N=36. Dabrafenib + trametinib showed an ORR of 64% (23/36) with a median follow-up of 15.9 months in previously untreated BRAFV600E-mutant metastatic NSCLC.. (First curated: 2020-04-16)
Changed Selpercatinib in Non-small cell lung cancer with RET Fusion, KIF5B-RET fusion, CCDC6-RET fusion, NCOA4-RET fusion, KIF13A-RET fusion, KIAA1549L-RET fusion, KIAA1468-RET fusion, PRKAR1A-RET fusion: 1: Tier changed: 1B. (First curated: 2023-10-29)
Changed Selpercatinib in Non-small cell lung cancer with RET Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion: 1: Tier changed: 1B. (First curated: 2020-05-08)

31 August, 2025 (Version: 20250831AU)

New Abemaciclib in Leydig cell tumour with CDK4 Amplification: 4: Case report. Targeting CDK4 amplifications in metastatic Leydig cell tumor with abemaciclib showed significant tumor shrinkage (RECIST-equivalent partial response) with no major adverse events. References: 40825166
New Tazemetostat in Ovarian small cell carcinoma with SMARCA4 Loss-of-function mutations: 4: Case report. 32-year-old patient with small-cell carcinoma of ovary hypercalcemic type (SCCOHT) treated with off-label tazemetostat (EZH2 inhibitor) achieved durable response but developed secondary T-cell acute lymphoblastic lymphoma (T-ALL), suggesting dual role of epigenetic therapy in tumor suppression and potential oncogenesis. References: 39167815

21 August, 2025 (Version: 20250821AU)

New Larotrectinib in Infantile Fibrosarcoma, Solid Tumors with NTRK1 TMP3-NTRK1 fusion, DCTN1-NTRK1 fusion, LMNA-NTRK1 fusion, BCAN-NTRK1 fusion, TPR-NTRK1 fusion: 3: Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy. References: 39652801
New Larotrectinib in Solid Tumors with NTRK2 AFAP1-NTRK2 fusion: 3: Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy. References: 39652801
New Larotrectinib in Infantile Fibrosarcoma, Solid Tumors with NTRK3 ETV6-NTRK3 fusion, VIM-NTRK3 fusion, EML4-NTRK3 fusion, RBPMS-NTRK3 fusion: 3: Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy. References: 39652801

18 August, 2025 (Version: 20250818AU)

New Tazemetostat in Solid tumours, Atypical teratoid rhabdoid tumour, Malignant rhabdoid tumor, Ewing sarcoma, Epithelioid sarcoma, Histiocytosis, Renal medullary carcinoma, Hepatocellular carcinoma, Ependymoma, Chordoma, Peripheral T-cell lymphoma with EZH2 Y646C, Y646F, Y646H, Y646N, Y646S, A682G, A682V, A692V: R2: Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%). References: 37228094
New Tazemetostat in Solid tumours, Atypical teratoid rhabdoid tumour, Malignant rhabdoid tumor, Ewing sarcoma, Epithelioid sarcoma, Histiocytosis, Renal medullary carcinoma, Hepatocellular carcinoma, Ependymoma, Chordoma, Peripheral T-cell lymphoma with SMARCB1 Oncogenic mutations, Loss of protein expression: R2: Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%). References: 37228094
New Tazemetostat in Solid tumours, Atypical teratoid rhabdoid tumour, Malignant rhabdoid tumor, Ewing sarcoma, Epithelioid sarcoma, Histiocytosis, Renal medullary carcinoma, Hepatocellular carcinoma, Ependymoma, Chordoma, Peripheral T-cell lymphoma with SMARCA4 Oncogenic mutations, Loss of protein expression: R2: Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%). References: 37228094

17 August, 2025 (Version: 20250817AU)

New GSK126, Tazemetostat in Ovarian small cell carcinoma with SMARCA4 Oncogenic mutations: 4: Preclinical study. SCCOHT tumor samples (N=24). 80% (19/24) showed strong EZH2 expression; re-expression of SMARCA4 suppressed EZH2. SCCOHT cells hypersensitive to EZH2 inhibitors (GSK126, EPZ-6438), inducing cell cycle arrest, apoptosis, differentiation, and improved survival in xenograft models. References: 28444909

08 August, 2025 (Version: 20250808AU)

New VX-970 in Prostate cancer with ATM Oncogenic mutations, Deletion: 4: Preclinical study. ATM loss in prostate cancer models did not significantly increase sensitivity to PARP inhibition but robustly sensitized to ATR inhibition, suggesting ATM-altered tumors may benefit more from ATR inhibitors than PARP inhibitors. References: 32127357

06 August, 2025 (Version: 20250806AU)

Changed Pemigatinib in Cervical cancer with FGFR2 : 3: Alterations changed: C382R (G380R). (First curated: 2023-05-05)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : 3: Alterations changed: C382R (G380R), I291_Y308del, Extracellular domain deletion, Y375C, W290CC382R, I291_Y308del, Extracellular domain deletion, Y375C, W290C. (First curated: 2023-05-05)
Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 3: Alterations changed: C382R (G380R), W290CC383R, W290C. (First curated: 2022-07-26)
Changed Pemigatinib in Cervical cancer, Endometrial cancer with FGFR2 : 3: Alterations changed: C382R (G380R). (First curated: 2024-07-19)
Changed Pemigatinib in Urothelial carcinoma, Glioblastoma, Cervical cancer, Endometrial cancer with FGFR3 : 3: Alterations changed: FGFR3-TACC3 fusion, Y375C (Y373C)FGFR3-TACC3 fusion, FGFR3 Y373C. (First curated: 2024-07-19)
Changed Pemigatinib in Urothelial carcinoma with FGFR3 : 3: Alterations changed: Fusion, R248C, S249C, S764fs*6, G372C (G370C), S373C (S371C), Y373C (Y375C)Fusion, R248C, S249C, S764fs*6, G370C, S371C, Y373C. (First curated: 2025-02-06)
Changed Erdafitinib in Urothelial carcinoma with FGFR3 : 3: Alterations changed: S249C, Y375C (Y373C), R248C, G372C (G370C), R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusionS249C, Y373C, R248C, G370C, R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusion. (First curated: 2025-02-06)
Changed Pemigatinib in Urothelial carcinoma with FGFR3 : 3: Alterations changed: Y375C (Y373C). (First curated: 2023-05-05)
Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N549K (N550K)BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K. (First curated: 2025-01-09)
Changed Lirafugratinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: FGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D (N550D), N549K (N550K), N549H, V564I, E565A, L617V, K641N, K659MFGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M. (First curated: 2024-09-25)
Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: Fusion and N549D (N550D), Fusion and N549K (N550K), Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642I, Fusion and K642R, Fusion and K660MFusion and N550D, Fusion and N550K, Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642I, Fusion and K642R, Fusion and K660M. (First curated: 2023-01-23)
Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: Fusion and N549D (N550D), Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642RFusion and N550D, Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642R. (First curated: 2023-01-23)
Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: K310R, M537I, N549D (N550D), N549K (N550K), N549H (N550H), V564I, E565A, L617V, K641N, K659MK310R, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M. (First curated: 2024-09-25)
Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: K310R, M537I, N549H (N550H), V564I, E565A, L617V, K641N, K659MK310R, M537I, N549H, V564I, E565A, L617V, K641N, K659M. (First curated: 2024-09-25)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: K310R, M537I, N549H (N550H), V564I, K641N, K659MK310R, M537I, N549H, V564I, K641N, K659M. (First curated: 2024-09-25)
Changed Gunagratinib in Solid tumours with FGFR2 : 4: Alterations changed: N549H (N550H), V564I, K659NN549H, V564I, K659N. (First curated: 2022-01-04)
Changed AZD4547, Infigratinib, E7090, Erdafitinib, Futibatinib, Pemigatinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: N549S, N549H (N550H). (First curated: 2023-02-22)
Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: N549H (N550H), N549K (N550K), E566A, E566G, L618M, L618VN550H, N550K, E566A, E566G, L618M, L618V. (First curated: 2025-01-09)
Changed Futibatinib in Solid tumours with FGFR2 : 4: Alterations changed: N549H (N550H), V565I, V565L, E566G, K660MN550H, V565I, V565L, E566G, K660M. (First curated: 2022-07-27)
Changed Futibatinib in Cholangiocarcinoma with FGFR2 : 4: Alterations changed: N549K (N550K), N549D (N550D), K660MN550K, N550D, K660M. (First curated: 2025-01-09)
Changed Dovitinib in Endometrial cancer with FGFR2 : 4: Alterations changed: S252W, N549K (N550K), C382R, Oncogenic mutationsS252W, N549K, C382R, Oncogenic mutations. (First curated: 2020-07-21)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N549K (N550K)BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K. (First curated: 2025-01-09)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549K (N550K), N549D (N550D), N549H (N550H), N549F, M537I, V564I, V564F, V564L, L617V, K641R, K569MN549K, N549D, N549H, N549F, M537I, V564I, V564F, V564L, L617V, K641R, K569M. (First curated: 2024-07-19)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549K (N550K), N549H (N550H), E565A, L617V, K641R, K659MN549K, N549H, E565A, L617V, K641R, K659M. (First curated: 2021-07-06)
Changed Dovitinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549S, N549H (N550H). (First curated: 2023-02-22)
Changed Infigratinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549D (N550D), N549K (N550K), V563I, V565I, V565L, E566A, E566G, K642I, L642R, K660MN550D, N550K, V563I, V565I, V565L, E566A, E566G, K642I, L642R, K660M. (First curated: 2023-01-23)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549D (N550D), N549K (N550K), V565I, V565L, K642I, K660MN550D, N550K, V565I, V565L, K642I, K660M. (First curated: 2023-01-23)
Changed Pemigatinib, Infigratinib, Erdafitinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549H (N550H), N549K (N550K), E566A, E566G, L618M, L618VN550H, N550K, E566A, E566G, L618M, L618V. (First curated: 2025-01-09)
Changed AZD4547, Infigratinib in Solid tumours with FGFR2 : R2: Alterations changed: N549H (N550H), V565I, V565L, E566G, K660MN550H, V565I, V565L, E566G, K660M. (First curated: 2022-07-27)
Changed Pemigatinib,Infigratinib, Erdafitinib, E7090, Zoligratinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549K (N550K), N549D (N550D), K660MN550K, N550D, K660M. (First curated: 2025-01-09)
Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: N549K (N550K), V565L, K642I, K660MN550K, V565L, K642I, K660M. (First curated: 2023-01-23)
Changed Infigratinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: V564F, N549H (N550H), N549K (N550K), E565A, L617V, K641R, K659MV564F, N549H, N549K, E565A, L617V, K641R, K659M. (First curated: 2023-02-22)
Changed Infigratinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: V564F, V564L, N549D (N550D), N549H (N550H), N549K (N550K), E565A, V564I, L617VV564F, V564L, N549D, N549H, N549K, E565A, V564I, L617V. (First curated: 2024-09-25)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: V564F, V564L, N549D (N550D), N549K (N550K), E565A, L617VV564F, V564L, N549D, N549K, E565A, L617V. (First curated: 2024-09-25)
Changed Erdafitinib in Cholangiocarcinoma with FGFR2 : R2: Alterations changed: V564F, V564L, N549K (N550K), N549D (N550D)V564F, V564L, N549K, N549D. (First curated: 2024-09-25)
Changed Infigratinib, AZD4547, Zoligratinib, Dovitinib, Ponatinib in Solid tumours with FGFR2 : R2: Alterations changed: V565I, N549K (N550K), V564M, V564FV565I, N550K, V564M, V564F. (First curated: 2020-05-22)

30 July, 2025 (Version: 20250730AU)

New Daratumumab + Bortezomib + Lenalidomide + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1B: Phase 3 PERSEUS trial. NCT03710603. N=709. Subcutaneous daratumumab added to VRd induction, consolidation, and lenalidomide maintenance significantly improved PFS (84.3% vs 67.7% at 48 months, HR 0.42) and ORR (87.9% vs 70.1%) and MRD-neg ative rate (75.2% vs 47.5%) in transplantation-eligible newly diagnosed multiple myeloma. Note that CD38 is a constitutively expressed target in myeloma and is not required for therapy selection. References: 38084760
New Amivantamab + Lazertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 1B: Phase 3. MARIPOSA. NCT04487080. N=1074. In previously untreated EGFR-mutated NSCLC, a 2:2:1 randomized trial compared amivantamab-lazertinib vs osimertinib vs lazertinib. Amivantamab-lazertinib demonstrated superior PFS compared to osimertinib (23.7 vs 16.6 months; HR 0.70, 95% CI 0.58–0.85). ORR was similar between groups (86% vs 85%), but median response duration favored amivantamab-lazertinib (25.8 vs 16.8 months). OS HR was 0.80 (95% CI 0.61–1.05). References: 38924756
New Enfortumab vedotin + Pembrolizumab in Urothelial carcinoma with NECTIN4 Protein expression: 1B: Not PBS listed. TGA approved for first line therapy with Pembrolizumab. Phase 3 EV-302 trial. NCT04223856. N=886. Enfortumab vedotin + pembrolizumab significantly prolonged PFS (12.5 vs 6.3 months; HR 0.45) and OS (31.5 vs 16.1 months; HR 0.47) versus platinum-based chemotherapy in untreated advanced urothelial cancer. Nectin-4 is constitutively expressed in urothelial carcinoma and biomarker selection is not required. PD-L1 does not have differential predictive effect on therapy outcomes. References: 38446675
New Asciminib in Chronic myelogenous leukaemia with ABL1 BCR-ABL1 Fusion: 2: Phase 3. ASC4FIRST. NCT04971226. N=405. Asciminib achieved a significantly higher major molecular response (MMR) at week 48 (67.7%) vs investigator-selected TKIs (49.0%; difference 18.9%) and vs imatinib (69.3% vs 40.2%; difference 29.6%) in newly diagnosed CML. References: 38820078
New Imlunestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: Phase 3 EMBER-3 trial. NCT04975308. N=874. Imlunestrant (N=331) demonstrated significantly longer PFS than standard therapy in ESR1-mutant patients (5.5 vs 3.8 months; HR 0.70; 95% CI 0.54-0.91; P<0.001) but showed no difference in the overall population (HR 0.87; 95% CI 0.72-1.04; P=0.12). Imlunestrant-abemaciclib combination (N=213) significantly improved PFS over imlunestrant monotherapy (9.4 vs 5.5 months; HR 0.57; 95% CI 0.44-0.73; P<0.001). References: 39660834
New Imlunestrant + Abemaciclib in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression: 2: Phase 3 EMBER-3 trial. NCT04975308. N=874. Imlunestrant (N=331) demonstrated significantly longer PFS than standard therapy in ESR1-mutant patients (5.5 vs 3.8 months; HR 0.70; 95% CI 0.54-0.91; P<0.001) but showed no difference in the overall population (HR 0.87; 95% CI 0.72-1.04; P=0.12). Imlunestrant-abemaciclib combination (N=213) significantly improved PFS over imlunestrant monotherapy (9.4 vs 5.5 months; HR 0.57; 95% CI 0.44-0.73; P<0.001). References: 39660834
New Ziftomenib in Acute myeloid leukaemia with KMT2A Rearrangement: 3: Phase 1/2 KOMET-001. NCT04067336. N=83. Ziftomenib showed 25% complete remission or remission with partial hematologic recovery in 36 KMT2A rearrangement/NPM1 mutation patients at 600 mg (recommended phase 2 dose), including 35% remission rate in 20 NPM1 mutation patients. References: 39401509
New Atezolizumab + Carboplatin + Paclitaxel in Endometrial cancer with Mismatch repair Deficient: 2: Phase 3 AtTEnd trial. NCT03603184. N=551. Median PFS was not estimable (95% CI 12.4-NE) for atezolizumab vs 6.9 months (6.3-10.1) for placebo in dMMR endometrial cancer (HR 0.36, p=0.0005); overall PFS 10.1 vs 8.9 months (HR 0.74, p=0.022). Median OS 38.7 vs 30.2 months (HR 0.82, log-rank p=0.048), with trial continuing for OS final analysis. References:
New Ziftomenib in Acute myeloid leukaemia with NPM1 Oncogenic mutation: 3: Phase 1/2 KOMET-001. NCT04067336. N=83. Ziftomenib showed 25% complete remission or remission with partial hematologic recovery in 36 KMT2A rearrangement/NPM1 mutation patients at 600 mg (recommended phase 2 dose), including 35% remission rate in 20 NPM1 mutation patients. References: 39401509
New Belantamab mafodotin + Bortezomib + Dexamethasone in Multiple myeloma with TNFRSF17 Protein expression: 2: Phase 3. DREAMM-7. NCT04246047. N=494. Belantamab mafodotin, bortezomib, dexamethasone (BVd) significantly improved PFS (36.6 vs 13.4 months, HR 0.41) over daratumumab, bortezomib, dexamethasone (DVd) in relapsed/refractory multiple myelo ma, with 84% vs 73% OS at 18 months, 25% vs 10% MRD-negative responses. Note that BCMA is a constitutively expressed target in myeloma and is not required for therapy selection. References: 38828933
New Belantamab mafodotin + Pomalidomide + Dexamethasone in Multiple myeloma with TNFRSF17 Protein expression: 2: Phase 3 DREAMM-8. NCT04484623. N=302. BPd (belantamab mafodotin, pomalidomide, dexamethasone) improved progression-free survival (PFS) over PVd (71% vs 51% at 12 months, hazard ratio 0.52), with higher response rates (77% vs 72%) and deeper responses (40% vs 16% complete response). Note that BCMA is a constitutively expressed target in myeloma and is not required for therapy selection. References: 38828951
New Gedatolisib + Palbociclib + Letrozole, Gedatolisib + Palbociclib + Fulvestrant in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3: Phase 1b. Dose expansion groups of NCT02684032. N=103. ORR was 85.2% in first-line group A, 61.5% in group B, 25.0% in group C, and 55.6% in group D. Adverse events: neutropenia (63%), stomatitis (27%), rash (20%), and hyperglycaemia (6%). No treatment-related deaths. Responses observed in both wild-type and mutated PIK3CA tumours. References: 38547892
New IMGN632 in Acute myeloid leukaemia with IL3RA Overexpression: 3: Phase 1/2 study. IMGN632. NCT03386513. N=91. Schedule A (n=68), Schedule B (n=23). No maximum tolerated dose defined; 0.045 mg/kg selected as RP2D. ORR 21% (95% CI 8-40; 6/29), composite CR 17% (5/29). Dose-limiting toxicities observed at 0.180, 0.300, 0.450 mg/kg. Phase 1b/2 study initiated with azacitidine and venetoclax in CD123+ AML. Note CD123 expression is not signficantly correlated with response. References: 38423051
New Alpelisib + Fulvestrant in Breast cancer with PIK3CA C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y: 3: Phase 2. BYLieve. NCT03056755. N=127 (Cohort A). Alpelisib + fulvestrant met primary endpoint of 6-month PFS (53.8%, 95% CI 44.4–63.0) in PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer post CDK4/6 inhibitor. Median PFS 8.0 months, OS 27.3 months. Adverse events included hyperglycaemia (29%) and rash (10%). Original curation: 2021-04-07. Updated 2025-07-30. References: 33794206, 39637900
New Cabozantinib in Paraganglioma, Phaeochromocytoma with SDHB Oncogenic mutations (germline): 3: Phase 2. Natalie Trial. NCT02302833. N=17. Cabozantinib achieved ORR of 25% (95% CI 7.3–52.4) in 16 evaluable patients with metastatic phaeochromocytoma/paraganglioma (MPPGs). Note the responses are independent of SDHB pathogenic variants, catecholamine secretion, or noradrenaline transporter expression. References: 38608693
New Atezolizumab + Docetaxel + Cisplatin + Fluorouracil in Anal cancer with CD274 Protein expression: 4: Phase 2. SCARCE C17-02 PRODIGE 60. NCT03519295. N=97 (64 in Atezolizumab + mDCF vs 33 in mDCF alone). 12-month PFS 45% (90% CI 35-55) vs 43% (29-58) in group A and B; in PD-L1 CPS ≥5, 70% vs 40% (interaction p=0.051). Higher grade 3-4 adverse events in group A (61% vs 42%), primary endpoint not met. References: 38547895
New CARv3-TEAM-E T cell in Glioblastoma with EGFR vIII: 4: Phase 1. INCIPIENT. NCT05660369. N=3. CARv3-TEAM-E T cells (dual-targeting EGFRvIII and wild-type EGFR) induced rapid tumor regression (transient in 2/3) with no >grade 3 toxicity; one patient had durable response. Liquid biopsy detected EGFR copy number decline. Contrasts with prior single-antigen CAR T trials limited by tumor heterogeneity and antigen loss. References: 38477966
Removed Alpelisib + Fulvestrant in Breast cancer with PIK3CA alterations E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y: Tier 3 (First curated: 2021-04-07)
Changed Capmatinib in Non-small cell lung cancer with MET Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation: 2: Comments changed: Not TGA approved. FDA approved 10/8/2022. Phase 2. GEOMETRY mono-1. NCT02414139. N=373. ORR in METex14 NSCLC was 68% (60 treatment-naive) and 44% (100 previously treated). Median follow-up 46.4 and 66.9 months respectively.\Not TGA approved; FDA approved 10/8/2022; GEOMETRY mono-1: ORR 41% in 69 previously treated patients. Median DOR 9.7 months. ORR 68% in 28 treatment naive patients. Median DOR 12.6 months.. References changed: 32877583, 39362249, 10.1200/JCO.2019.37.15_suppl.900432877583, 10.1200/JCO.2019.37.15_suppl.9004. (First curated: 2020-05-06)

18 July, 2025 (Version: 20250718AU)

Changed Therapy in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4: Therapy changed: NeladalkibNVL-655. (First curated: 2025-04-30)
Changed Therapy in Solid tumours, Non-small cell lung cancer with ALK I1171N and D1203N: R2: Therapy changed: NeladalkibNVL-655. (First curated: 2025-04-30)

17 July, 2025 (Version: 20250717AU)

New Afatinib, Neratinib, Dacomitinib in Solid tumours with ERBB4 E715K, R687K: 4: Preclinical study. Unbiased functional genetics screen identifies rare activating ERBB4 mutations (E715K, R687K) promoting hyperactivity in cell models, growth in 2D/3D cultures, and in vivo tumor growth; all mutants sensitive to pan-ERBB inhibitors afatinib, neratinib, dacomitinib. References: 36860695
New Cinrebafusp alfa in Solid tumours with ERBB2 Overexpression, Amplification: 4: Phase 1. NCT03330561. First-in-human study. Cinrebafusp alfa, a HER2/4-1BB bispecific molecule, was evaluated in N=40 patients with previously treated HER2-positive malignancies. The objective response rate was 12.5%, with confirmed responses of 28.6% at 8 mg/kg and 25.0% at 18 mg/kg. Disease control rate was 52.5%, and maximum tolerated dose was not reached. References: 39235868

14 July, 2025 (Version: 20250714AU)

Changed Therapy in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4: Therapy changed: RipretinibRepretinib. (First curated: 2025-07-07)
Changed Therapy in Gastrointestinal stromal tumour with KIT T670I, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2: Therapy changed: RipretinibRepretinib. (First curated: 2025-07-07)
Changed Therapy in Gastrointestinal stromal tumour with PDGFRA D842V, D842V and V654A, D842V and T674R: R2: Therapy changed: Imatinib, Sunitinib, Regorafenib, Ripretinib, Nintedanib, Bezuclastinib, IDRX-42, NB003Imatinib, Sunitinib, Regorafenib, Repretinib, Nintedanib, Bezuclastinib, IDRX-42, NB003. (First curated: 2025-07-07)

11 July, 2025 (Version: 20250711AU)

Changed AZD6422 with CLDN18 Protein expression: 4: Cancer type(s) changed: Gastric cancer, Pancreatic adenocarcinoma, Oesophageal cancerGastric cancer, Pancreatic adenocarcinoma, Oessophageal cancer (First curated: 2025-07-09)

09 July, 2025 (Version: 20250709AU)

New Rucaparib, Olaparib, Talazoparib in Prostate cancer with CDK12 Truncating mutations, Kinase domain mutations: 4: CRISPR/Cas9 models and the TRITON2 trial (N=11) demonstrate that CDK12-deficient prostate cancer cells are more sensitive to PARPi, with biallelic truncation mutants showing higher sensitivity (55% PSA reduction) than kinase domain mutants. In TRITON2, 6 of 11 patients responded, with 4/6 achieving stable disease and 2/6 progressive disease by RECIST. Response to rucaparib monotherapy varied by CDK12 mutation type and zygosity (monoallelic, gene arrangements, biallelic). References: 39321214
New AZD6422 in Gastric cancer, Pancreatic adenocarcinoma, Oessophageal cancer with CLDN18 Protein expression: 4: Preclinical study. AZD6422. NCT05981235. Armored CAR-T targeting CLDN18.2 with TGF-beta resistance and optimized manufacturing showed antitumor activity in patient-derived xenograft models of gastric, pancreatic, and esophageal cancers with varying CLDN18.2 and TGF-beta levels. References: 39321207

07 July, 2025 (Version: 20250707AU)

New IDRX-42 in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New NB003 in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Repretinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Nintedanib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, T670I, D820A, N822K, A829P, V654A and D820A, V654A and N822K, V654A and A829P: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Sunitinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, K642E, V654A, T670I, V654A and D820A: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Avapritinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, Exon11 deletion, V654A, D816A, D820A, N822K, A829P, V654A and D820A, V654A and N822K, V654A and A829P, D842V: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Imatinib, Regorafenib in Gastrointestinal stromal tumour with KIT Exon11 deletion: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Bezuclastinib in Gastrointestinal stromal tumour with KIT Exon11 deletion, D820A, A829P: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Avapritinib in Gastrointestinal stromal tumour with PDGFRA D842V: 4: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Imatinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, K642E, V654A, T670I, D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Regorafenib in Gastrointestinal stromal tumour with KIT A502_Y503dup, K642E, V654A, T670I, D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Bezuclastinib in Gastrointestinal stromal tumour with KIT A502_Y503dup, K642E, V654A, T670I, D816A, N822K, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Nintedanib in Gastrointestinal stromal tumour with KIT D816A, A502_Y503dup and N822K, V654A and D816A: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Sunitinib in Gastrointestinal stromal tumour with KIT D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and N822K, V654A and A829P: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Avapritinib in Gastrointestinal stromal tumour with KIT K642E, T670I, A502_Y503dup and N822K, V654A and D816A: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New IDRX-42 in Gastrointestinal stromal tumour with KIT T670I, V654A and D816A, V654A and D820A: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Repretinib in Gastrointestinal stromal tumour with KIT T670I, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New NB003 in Gastrointestinal stromal tumour with KIT T670I, V654A and D820A, V654A and N822K, V654A and A829P: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Avapritinib in Gastrointestinal stromal tumour with PDGFRA D842V and V654A, D842V and T674R: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
New Imatinib, Sunitinib, Regorafenib, Repretinib, Nintedanib, Bezuclastinib, IDRX-42, NB003 in Gastrointestinal stromal tumour with PDGFRA D842V, D842V and V654A, D842V and T674R: R2: Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors. References: 38408285
Changed Ivosidenib in Cholangiocarcinoma with IDH1 R132: 1: Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months). Update 2025-07-07.TGA approved. Not PBS listed. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months).. (First curated: 2020-05-27)
Changed Ivosidenib in Cholangiocarcinoma with IDH1 R132: 1: Tier changed: 1B. Comments changed: TGA approved. PBS listed. Phase 3. ClarIDHy trial. Final OS result. In IDH1 mutant cholangiocarcinoma patients, Ivosidenib resulted in median OS of 10.3 months vs 7.5 months (placebo; adjusted for crossover 5.1 months). Update 2025-07-07TGA approved. Not PBS listed. Phase 3. ClarIDHy trial. Final OS result. In IDH1 mutant cholangiocarcinoma patients, Ivosidenib resulted in median OS of 10.3 months vs 7.5 months (placebo; adjusted for crossover 5.1 months).. (First curated: 2023-07-31)

04 July, 2025 (Version: 20250704AU)

New Crizotinib in Non-small cell lung cancer with MET Exon 14 skipping mutation, Exon 16 mutation, H1094Y, c.3028+1G>T, c.3028+1G>A, c.3028G>A, c.3028+1G>C, C.2888-27_2888-2delinsC, c.2935_2939del, c.2888-14_2888-4del, c.2888-17_2888-6del c.2888-18_2888-9del, c.2888-20_2888-11del, c.3028+1G>C, c.3028G>C, c.3028G>T, c.3028G>C, c.3028+2T>C, C.3028+2T>A, C.3028+2T>A, c.3028+3A>G, c.3280C>T: 3: Phase 2. Drug Rediscovery Protocol. NCT0295234. N=30. Crizotinib achieved clinical benefit in 70.8% of MET-mutated non-small cell lung cancer patients (CB: 70.8% [95% CI, 48.9-87.4]), with ORR 62.5% (95% CI, 40.6-81.2). Median PFS 10.2 months (95% CI, 6.0-20.1), OS 13.0 months (95% CI, 9.0-not available). One CR patient harbored a tyrosine kinase domain mutation (p.H1094Y); others had MET exon 14 skipping mutations. References: 39352721

02 July, 2025 (Version: 20250702AU)

New Lorlatinib, Crizotinib, Alectinib, Ceritinib, Brigatinib, Entrectinib, Repotrectinib, Gilteritinib in Non-small cell lung cancer with LTK CLIP1-LTK fusion: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Alectinib in Non-small cell lung cancer with LTK I565N, F568C, G663A: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Ceritinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, G596R, D597N, G663A: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Gilteritinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, L592F, D597N, L650F, G663A: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Lorlatinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, L592F, G596R, D597N, G663A: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Brigatinib, Entrectinib in Non-small cell lung cancer with LTK I565N, L590M, D597N, G663A: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Repotrectinib in Non-small cell lung cancer with LTK I565N, L590M, L592F, G596R, D597N, G663A: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Crizotinib in Non-small cell lung cancer with LTK L592F: 4: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Brigatinib, Entrectinib in Non-small cell lung cancer with LTK F568C, L592F, G596R, L650F: R2: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Repotrectinib in Non-small cell lung cancer with LTK F568C, L650F: R2: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Gilteritinib in Non-small cell lung cancer with LTK G596R: R2: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Crizotinib in Non-small cell lung cancer with LTK I565N, F568C, L590M, G596R, D597N, L650F, G663A: R2: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Alectinib in Non-small cell lung cancer with LTK L590M, L592F, G596R, D597N, L650F: R2: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Ceritinib in Non-small cell lung cancer with LTK L592F, L650F: R2: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Lorlatinib in Non-small cell lung cancer with LTK L650F: R2: Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity. References: 38575808
New Trastuzumab + Nivolumab in Breast cancer, Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 3: Phase Ib. DS8201-A-U105. NCT03523572. N=82. T-DXd (5.4 mg/kg) plus nivolumab 360 mg every 3 weeks showed confirmed objective response rates (cORR) of 65.6% (HER2-positive mBC, cohort 1), 50.0% (HER2-low mBC, cohort 2), and 36.7% (HER2-high mUC who had received prior platinum-based chemotherapy, cohort 3). Median PFS was 11.6 months (cohort 1), 7.0 months (cohort 2), and 6.9 months (cohort 3). Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 20.7% (cohort 1) and 20.0% (cohort 3). In Cohort 4 (n=4, HER2-low advanced urothelial cancer/mUC), 2 responders were also seen. Safety consistent with T-DXd monotherapy, though higher TEAE discontinuation rates observed. References: 39405343

01 July, 2025 (Version: 20250701AU)

New Berzosertib in Solid tumours, Leiomyosarcoma with ARID1A Oncogenic mutation: R2: Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit. References: 39453756
New Berzosertib in Solid tumours, Synovial sarcoma, Non-small cell lung cancer, Pancreatic adenocarcinoma, Ovarian cancer with ATM Oncogenic mutation: R2: Phase 2 trial. NCT03718091. T2 cohort. N=6. ATM-mutant solid tumors treated with Berzosertib had a median PFS of 62 days. No response was seen with stable disease as best response in some patients. References: 39453756
New Berzosertib in Leiomyosarcoma, Osteosarcoma with ATRX Oncogenic mutation: R2: Phase 2 trial. NCT03718091. Cohort T1: ATRX-mutant leiomyosarcoma. N=10. Median PFS was short (62 days) with progressive disease as best response in most patients. Evidence of target engagement by berzosertib was seen, but PFS did not correlate with pCHK1 or other pharmacodynamic biomarkers. Increased SLFN11 expression on-treatment correlated with longer PFS (61 vs 33 days). References: 39453756
New Palbociclib in Solid tumours with CDK4 Amplification: R2: Phase 2. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C. N=43. Palbociclib showed limited activity in CDK4/6-amplified tumors with ORR of 4% (1/25) in centrally confirmed cohort, median PFS 2.0 months and OS 8.8 months; partial responses and stable disease observed only in CDK4-amplified tumors, with CNS tumors noted as potential candidates for further investigation. References: 39437014
New Palbociclib in Solid tumours with CDK6 Amplification: R2: Phase 2. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C. N=43. Palbociclib showed limited activity in CDK4/6-amplified tumors with ORR of 4% (1/25) in centrally confirmed cohort, median PFS 2.0 months and OS 8.8 months; partial responses and stable disease observed only in CDK4-amplified tumors, with CNS tumors noted as potential candidates for further investigation. References: 39437014
New Binimetinib in Low-grade serous ovarian cancer with ERBB3 Amplification: R2: Case series. KRAS-mutated LGSOC patient with MEK inhibitor resistance developed aggressive brain metastases associated with ERBB3 amplification and aberrant ERBB3–MYC signaling, suggesting potential resistance mechanisms and need for combinatorial strategies. References: 31836588
New Berzosertib in Solid tumours, Leiomyosarcoma with FBXW7 Oncogenic mutation: R2: Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit. References: 39453756
New Berzosertib in Solid tumours, Prostate cancer with MYC Amplification: R2: Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit. References: 39453756
New Berzosertib in Gastrointestinal stromal tumour with SDHA Oncogenic mutation: R2: Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756
New Berzosertib in Gastrointestinal stromal tumour with SDHB Oncogenic mutation: R2: Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756
New Berzosertib in Gastrointestinal stromal tumour with SDHC Oncogenic mutation: R2: Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756
New Berzosertib in Gastrointestinal stromal tumour with SDHD Oncogenic mutation: R2: Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response. References: 39453756
Changed YL201 with CD276 Protein expression: 3: Cancer type(s) changed: Solid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer, Pulmonary lymphoepithelioma-like carcinomaSolid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer, Lymphoepithelioma-like carcinoma (First curated: 2024-09-14)

29 June, 2025 (Version: 20250629AU)

New Acimtamig in Peripheral T-cell lymphoma with TNFRSF8 Protein expression: 3: Phase 2 study. NCT04101331. N=108. In patients with CD30-positive relapsed or refractory peripheral T-cell lymphomas, acimtamig exhibited an ORR of 32.4% with a CD30 positivity determined by Ber-H2 targeted IHC with CD30 expression confirmed in ≥1% of tumor cells, and a median DoR of 2.3 months. References: 39531538
New BG-C477 in Solid tumours with CEACAM5 Protein expression: 4: Preclinical study. BG-C477, a CEACAM5-targeting ADC with topoisomerase 1 inhibitor payload, demonstrates cytotoxicity and antitumor efficacy in various CEACAM5-expressing cancer models. First-in-human trial ongoing (NCT06596473). References: 10.1158/1538-7445.AM2025-5461
New Pembrolizumab + Cisplatin + Gemcitabine, Pembrolizumab + Carboplatin + Gemcitabine in Urothelial carcinoma with Tumour Mutational Burden High: 4: Phase 3 KEYNOTE-361 trial. NCT02853305. N=993. Primary endpoints of PFS (HR 0.78, P=0.0033) and OS (HR 0.86, P=0.0407) were not met for pembrolizumab plus chemotherapy versus chemotherapy. TMB as a continuous variable was significantly associated with improved ORR, PFS, and OS in pembrolizumab monotherapy (one-sided P<0.001, P<0.001, P=0.007), with highest benefits observed in patients with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 versus chemotherapy alone. Cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1) were prespecified. References: 39475359
New Pembrolizumab + Cisplatin + Gemcitabine, Pembrolizumab + Carboplatin + Gemcitabine in Urothelial carcinoma with CD274 Protein expression: 4: Phase 3 KEYNOTE-361 trial. NCT02853305. N=993. Primary endpoints of PFS (HR 0.78, P=0.0033) and OS (HR 0.86, P=0.0407) were not met for pembrolizumab plus chemotherapy versus chemotherapy. TMB as a continuous variable was significantly associated with improved ORR, PFS, and OS in pembrolizumab monotherapy (one-sided P<0.001, P<0.001, P=0.007), with highest benefits observed in patients with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 versus chemotherapy alone. Cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1) were prespecified. References: 39475359
Changed Brentuximab Vedotin in Anaplastic large cell lymphomaProtein expression: 1: Biomarker changed: TNFRSF8CD30. (First curated: 2020-06-15)
Changed Brentuximab Vedotin in Cutaneous T-cell lymphomaProtein expression: 1: Biomarker changed: TNFRSF8CD30. (First curated: 2020-06-15)
Changed Brentuximab Vedotin in Hodgkin’s lymphomaProtein expression: 1: Biomarker changed: TNFRSF8CD30. (First curated: 2020-06-15)
Changed YL201 with CD276 Protein expression: 3: Cancer type(s) changed: Solid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer, Lymphoepithelioma-like carcinoma Comments changed: Phase 1/1b trial. NCT05434234 and NCT06057922. N=312. YL201, a B7H3-targeting antibody-drug conjugate, demonstrated antitumor activity in heavily pretreated patients with objective response rates of 63.9% in ES-SCLC, 48.6% in NPC, and 54.2% in LELC, prompting ongoing phase 3 trials for SCLC and NPC. All tumors expressed B7H3, but no significant correlation was seen between B7H3 expression levels and response across different tumour types. Updated 2025-06-29Phase 1. NCT06057922 and NCT05434234. In patients with advanced solid tumors, single agent YL201 aided ORR was 74% in SCLC, 46% in NPC, and 32% in NSCLC (wild type especially in adenocarinoma and LELC); at ≥2.0 mg/kg dose level.. References changed: 40082695, 10.1016/j.annonc.2024.08.672. (First curated: 2024-09-14)

27 June, 2025 (Version: 20250627AU)

New Mivebresib in Small-cell lung cancer with MYC Amplification, Overexpression: 4: Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1. References: 38747975
New Mivebresib in Small-cell lung cancer with MYCN Amplification, Overexpression: 4: Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1. References: 38747975
New Sapanisertib in Non-small cell lung cancer with RICTOR Amplification: 4: Case report with translational studies. RICTOR amplification occurs in 8-13% of lung cancer cases and is associated with sensitivity to mTORC1/2 inhibitors; an 18-year-old patient with RICTOR-amplified lung cancer achieved tumor stabilization for over 18 months with dual mTORC1/2 inhibitors. References: 26370156
New Mivebresib in Small-cell lung cancer with MYCL Amplification, Overexpression: R2: Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1. References: 38747975

24 June, 2025 (Version: 20250624AU)

New Fulvestrant + Abemaciclib in Endometrial cancer with ESR1 Protein expression: 3: Phase 2 study. N=27. Fulvestrant plus Abemaciclib showed promising activity in hormone receptor-positive advanced or recurrent endometrial cancer with an ORR of 44% and median PFS of 9.0 months, with durable responses observed mainly in copy number-low/no specific molecular profile tumors. References: 39561275
New Larotrectinib, Entrectinib, Repotrectinib, Selitrectinib in High-grade gliomas, Low-grade gliomas, Central nervous system cancer with NTRK1 Fusions, TPM3-NTRK2 fusion, TPR-NTRK2 fusion, IRF2BP2-NTRK2 fusion, KIF21B-NTRK2 fusion, LMNA-NTRK2 fusion, MEF2D-NTRK2 fusion, ARHGEF2-NTRK2 fusion, PDP0E4IP-NTRK2 fusion, CGN-NTRK2 fusion, KIRREL-NTRK2 fusion: 3: Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment. References: 39625867
New Larotrectinib, Entrectinib, Repotrectinib, Selitrectinib in High-grade gliomas, Low-grade gliomas, Central nervous system cancer with NTRK2 Fusions, AGAP1-NTRK2 fusion, BEND5-NTRK2 fusion, STRN-NTRK2 fusion, KCTD8-NTRK2 fusion, KANK2-NTRK2 fusion, QKI-NTRK2 fusion, NACC2-NTRK2 fusion, KANK1-NTRK2 fusion, SPEC1L-NTRK2 fusion, GKAP1-NTRK2 fusion, KCTD16-NTRK2 fusion, CHAMP1-NTRK2 fusion, CCDC88A-NTRK2 fusion, DNM3-NTRK2 fusion, SBF2-NTRK2 fusion, UGDH-NTRK2 fusion, STMN1-NTRK2 fusion, ATP6V1A-NTRK2 fusion, VAMP4-NTRK2 fusion, SHANK1-NTRK2 fusion, SORBS1-NTRK2 fusion, ABI2-NTRK2 fusion, GNAI1-NTRK2 fusion, SOS1-NTRK2 fusion, DENND5A-NTRK2 fusion, C1orf112-NTRK2 fusion, TLE1-NTRK2 fusion, PHF20L1-NTRK2 fusion, CYP2E1-NTRK2 fusion, PAPPA-NTRK2 fusion: 3: Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment. References: 39625867
New Larotrectinib, Entrectinib, Repotrectinib, Selitrectinib in High-grade gliomas, Low-grade gliomas, Central nervous system cancer with NTRK3 Fusions, ETV6-NTRK3 fusion, EML4-NTRK3 fusion, BCR-NTRK3 fusion, KANK1-NTRK3 fusion, FOXJ2-NTRK3 fusion, MYO5A-NTRK3 fusion, MN1-NTRK3 fusion, EGR3-NTRK3 fusion, SPEC1L-NTRK3 fusion, SOX6-NTRK3 fusion: 3: Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment. References: 39625867
New Alisertib + Pembrolizumab in Head and neck squamous cell carcinoma with RB1 Deletion, Oncogenic mutations, Loss of protein expression: R2: Phase 1/2 trial. Alisertib + Pembrolizumab demonstrated no objective responses but achieved prolonged stable disease in several patients. Among 15 HPV-positive patients, 4 experienced stable disease ≥6 months. Median overall survival was 16.8 months and median progression-free survival was 1.4 months. References: 39589337

23 June, 2025 (Version: 20250623AU)

New Sacituzumab Govitecan in Triple-negative breast cancer with TACSTD2 Protein expression, Overexpression: 4: Phase 2 TROPiCS-03 basket trial. NCT03964727. N = 43. Objective response rate was 16% and clinical benefit rate was 28% in heavily pretreated advanced HNSCC patients receiving Sacituzumab Govitecan, with median duration of response, PFS, and OS being 4.2, 4.1, and 9.0 months. Note Trop 2 expression was assesed as an exploratory endpoint. Patients were enroleld prospectively as Trop2 expression is highly expressed in HNSCC. References: 39665770
New Selinexor + Docetaxel in Non-small cell lung cancer with KRAS+TP53 KRAS:Oncogenic mutations and NOT TP53:Alteration: 3: Phase 1/2 trial. N=40. Selinexor plus docetaxel showed activities in TP53 wild-type KRAS-mutant NSCLC patients with a median PFS of 7.4 months versus 1.8 months in TP53-altered cases, and response rates of 27% versus 9% respectively. References: 39651955
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 : 3: Alterations changed: Fusion, FGFR2-BICC1 fusion, FGFR2-RBM20 fusion, FGFR2-MRVI1 fusion, FGFR2-CROCC fusion, FGFR2-KIAA1598 fusion, FGFR2 I291_Y308del, FGFR2 W290C, FGFR2 Y375C, FGFR2 C382RFusion, FGFR2-BICC1 fusion, FGFR2-RBM20 fusion, FGFR2-MRVI1 fusion, FGFR2-CROCC fusion, FGFR2-KIAA1598 fusion, FGFR2 1291_Y308del, FGFR2 W290C, FGFR2 Y375C, FGFR2 C382R. (First curated: 2024-07-19)

22 June, 2025 (Version: 20250622AU)

New Sunitinib in Gastrointestinal stromal tumour with KIT Protein expression: 1: PBS reimbursed based on CD117 (c-KIT) IHC. Randomised controlled Phase 3 trial. NCT00075218. N=312. Median time to tumour progression was 27.3 weeks with sunitinib versus 6.4 weeks with placebo (HR 0.33; p<0.0001) in imatinib-resistant or intolerant gastrointestinal stromal tumour. References: 17046465
New Ipatasertib in Breast cancer, Endometrial cancer with AKT1 E17K: 3: Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers. References: 10.1200/JCO.2024.42.16_suppl.3092
New Ipatasertib in Head and neck squamous cell carcinoma with AKT1 E17K: 4: Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers. References: 10.1200/JCO.2024.42.16_suppl.3092
New Ipatasertib in Solid tumours except Breast cancer, Endometrial cancer with AKT1 E17K: R2: Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers. References: 10.1200/JCO.2024.42.16_suppl.3092
Removed Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF alterations V600E: Tier 2 (First curated: 2025-05-31)
Removed BET inhibitor in Solid tumours with BRD2 alterations Oncogenic mutations: Tier 4 (First curated: 2020-04-16)
Removed BET inhibitor in Solid tumours with BRD3 alterations Oncogenic mutations: Tier 4 (First curated: 2020-04-16)
Removed BET inhibitor in Solid tumours with BRDT alterations Oncogenic mutations: Tier 4 (First curated: 2020-04-16)
Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with STK11 alterations Oncogenic mutations: Tier R2 (First curated: 2020-04-25)
Changed Ibrutinib in Mantle cell lymphoma with CD20 Protein expression: 1: Comments changed: PBS reimbursed. Phase 2 study. NCT01236391. N=111. Ibrutinib showed a 68% overall response rate (21% complete response, 47% partial response) in patients with relapsed or refractory mantle-cell lymphoma, with median response duration of 17.5 months, median progression-free survival of 13.9 months, and 58% overall survival at 18 months.. (First curated: 2020-06-15)
Changed Atezolizumab in Non-small cell lung cancer with CD274+EGFR+ALK CD274:Protein expression and NOT EGFR:Oncogenic mutations and NOT ALK:fusion: 1: Tier changed: 1B. Comments changed: TGA approved. PBS reimbused. Phase 3 IMpower110 trial (NCT02409342, N=572) evaluated first-line atezolizumab in EGFR and ALK negative NSCLC patients with PD-L1 expression ≥1% on tumor cells or tumor-infiltrating immune cells covering ≥1% of tumor area. Atezolizumab significantly improved median OS compared to chemotherapy (20.2 vs 13.1 months, improvement of 7.1 months).TGA approved; IMPower110: First-line treatment in PD-L1 positive population (defined as positive stain on >=least 1% of tumour cells or tumor-infiltrating immune cells >= 1% of the tumor area), EGFR and ALK negative. Median OS: 20 vs 13 months (chemotherapy). (First curated: 2020-12-11)
Changed Brentuximab Vedotin in Hodgkin’s lymphoma with CD30 Protein expression: 1: Comments changed: PBS reimbursed for R/R disease. Phase 3 AETHERA trial: Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation significantly improved PFS (HR 0.57) in patients with Hodgkin's lymphoma at risk of relapse or progression.. (First curated: 2020-06-15)
Changed Gilteritinib in Acute myeloid leukaemia with FLT3 D835, I836, Internal tandem duplication: 1: Comments changed: PBS reimbursed. Phase 1-2 trial (NCT02014558) demonstrated gilteritinib was well tolerated in patients with relapsed or refractory acute myeloid leukaemia, with a maximum tolerated dose of 300mg/day, consistent FLT3 inhibition and antileukaemic activity, achieving 40% response rate. Phase 3 trial (NCT02421939, N=371) showed gilteritinib significantly improved overall survival (9.3 vs 5.6 months) and complete remission with full or partial hematologic recovery (34.0% vs 15.3%) compared to salvage chemotherapy in patients with relapsed or refractory FLT3-mutated AML.PBS reimbursed in R/R FLT3-mutant AML. (First curated: 2020-04-16)
Changed Therapy in Gastrointestinal stromal tumour with KIT Protein expression: 1: Therapy changed: Imatinib, Sunitinib. Comments changed: PBS reimbursed based on CD117 (c-KIT) IHC. Phase 2 trial. N=147. Imatinib mesylate resulted in a partial response in 53.7% of patients with advanced gastrointestinal stromal tumors, with median duration of response not reached after 24 weeks, and was well tolerated with mild-to-moderate adverse effects.PBS reimbursed based on CD117 (c-KIT) IHC. NCCN Category 1. References changed: 12181401, 17046465. (First curated: 2020-05-07)
Changed Ripretinib in Gastrointestinal stromal tumour with KIT Protein expression; Oncogenic mutations: 1: Comments changed: TGA approved. PBS Reimbursed for patients with GIST who received prior treatment with 3 or more kinase inhibitors. Phase3 INVICTUS trial. NCT03353753. Ripretinib significantly improved median PFS (6.3 months vs 1.0 month) compared with placebo in patients with advanced gastrointestinal stromal tumours resistant to approved treatments.TGA approved. PBS Reimbursed for patients with GIST who received prior treatment with 3 or more kinase inhibitors;. (First curated: 2020-05-20)
Changed Cetuximab, Panitumumab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 1: Comments changed: PBS reimbursed for RAS-wild-type metastatic colorectal cancers. N=329. Cetuximab plus irinotecan had a significantly higher ORR (22.9% vs 10.8%) and longer median TTP (4.1 vs 1.5 months) compared to cetuximab monotherapy in irinotecan-refractory metastatic colorectal cancer. In a meta-analysis of 9 RCTs (N=5948). anti-EGFR mAb therapy significantly improved PFS (HR 0.62) and OS (HR 0.87) in mCRC tumors without any RAS mutations, while no benefit was evident in tumors with RAS mutations.. (First curated: 2020-04-16)
Changed Enfortumab Vedotin in Urothelial carcinoma with NECTIN4 Protein expression: 1: Comments changed: TGA approved. PBS reimbursed. In Phase 2 EV-201 trial (N=125), enfortumab vedotin showed a confirmed objective response rate of 44% with 12% complete responses in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum and anti-PD-1/L1 therapy. In registrational Phase 3 EV-301 trial (NCT03474107, N=608), enfortumab vedotin significantly prolonged overall survival (12.88 months vs 8.97 months) and progression-free survival (5.55 vs 3.71 months) compared to chemotherapy in patients with advanced urothelial carcinoma previously treated with platinum-containing chemotherapy and PD-1 or PD-L1 inhibitor. Nectin-4 expression was not required for trial entry, given that it is highly expressed on majority of urothelial carcinoma cells.TGA approved. PBS reimbursed. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells.. (First curated: 2021-02-15)
Changed Imatinib in Chronic eosinophilic leukaemia with PDGFRA FIP1L1-PDGFRA Fusion; Fusion: 1: Comments changed: TGA approved. PBS reimbursed. Phase 2 study. Imatinib was effective in treating CEL with FIP1L1-PDGFRA or PDGFRB fusion genes, achieving 95% CHR and 75-87% CMR, with no molecular relapse observed at a median follow-up of 26.7 months, while HES patients without known molecular aberration showed a lower response rate.. (First curated: 2020-04-16)
Changed Medroxyprogesterone Acetate in Endometrial cancer with PGR Protein expression: 1: Comments changed: Standard of care. Phase 3 dose-response study. N=299. Oral medroxyprogesterone acetate (MPA) showed response rates of 25% (low-dose, 200mg/d) versus 15% (high-dose, 1000mg/d) in advanced or recurrent endometrial carcinoma, with median PFS of 3.2 and 2.5 months, and median OS of 11.1 and 7.0 months, respectively.. (First curated: 2020-06-18)
Changed Ibrutinib + Rituximab in Chronic lymphocytic leukaemia with CD20 Protein expression: 1B: Comments changed: TGA approved. Not PBS reimbursed. Phase 3 trial. NCT02048813. N=529. Ibrutinib-rituximab resulted in superior PFS (89.4% vs 72.9% at 3 years) and OS (98.8% vs 91.5% at 3 years) compared to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab in patients with previously untreated CLL.. (First curated: 2020-06-15)
Changed Ibrutinib, Ibrutinib + Rituximab in Waldenstroms macroglobulinaemia with CD20 Protein expression: 1B: Comments changed: Phase 3. iNNOVATE trial. N=150. Ibrutinib plus Rituximab significantly improved PFS (HR, 0.20) and major response rate (72% vs 32%) compared to placebo plus Rituximab in both previously treated and untreated Waldenstrom's macroglobulinemia patients.. (First curated: 2020-06-15)
Changed Pembrolizumab in Cervical cancer with CD274 Protein expression: 1B: Comments changed: TGA approved. In the Phase 1b KEYNOTE-028 trial (NCT02054806; n=24) in PD-L1-positive advanced cervical cancer, pembrolizumab achieved an ORR of 17% (4 confirmed partial responses; 3 stable disease). In the Phase 2 KEYNOTE-158 study (NCT02628067; n=98) in previously treated advanced cervical cancer, pembrolizumab produced an ORR of 12.2% (3 complete responses; 9 partial responses), with all responses occurring in tumors with CPS ≥ 1% by 22C3 pharmDx assay (ORR 15% in PD-L1-positive cohort).TGA approved. KEYNOTE-028: Phase 1b. ORR 17%. KEYNOTE-158: ORR 15%. PD-L1 positivity defined as CPS >= 1% (22C3 pharmDx assay).. (First curated: 2020-04-16)
Changed Daratumumab + Lenalidomide + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1B: Comments changed: TGA approved. Phase 3 POLLUX trial. NCT02076009. N=569. Daratumumab + lenalidomide + dexamethasone significantly improved PFS (HR, 0.37) and ORR (92.9% vs 76.4%) compared to lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma.. (First curated: 2020-06-15)
Changed Isatuximab-irfc + Pomalidomide + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1B: Comments changed: TGA approved. Phase 3 ICARIA-MM study. N = 307. Isatuximab + pomalidomide-dexamethasone significantly improved median PFS (11.5 months) compared to pomalidomide-dexamethasone (6.5 months) with HR of 0.596 in relapsed and refractory multiple myeloma patients.ICARIA-MM trial. (First curated: 2020-06-15)
Changed Polatuzumab vedotin + Bendamustine + Rituximab in Diffuse large B-cell lymphoma with CD79B Protein expression: 1B: Comments changed: Standard of care. TGA approved but not based on biomarker. Phase Ib/II trials demonstrated that polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) achieved superior outcomes compared to bendamustine and rituximab in transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma patients: complete response rate (40.0% vs 17.5%), progression-free survival (median 9.5 vs 3.7 months), and overall survival (median 12.4 vs 4.7 months). While CD79B is prognostic, CD79B expression alone does not correlate with response degree.Standard of care. Drug approved by TGA. CD79B is prognostic, but CD79B expression alone not associated with degree of response. (First curated: 2020-06-15)
Changed Amivantamab in Non-small cell lung cancer with EGFR Exon 20 insertion: 1B: Comments changed: TGA approved. Not PBS Listed. FDA accelerated approval 2021-05-21. Median PFS 8.3 months. "Phase 1 CHRYSALIS trial. N=81. Amivantamab, an EGFR-MET bispecific antibody, showed an ORR of 40% (3 complete responses) and median DOR of 11.1 months in patients with EGFR Exon20ins NSCLC progressing on platinum chemotherapy, with a median PFS of 8.3 months.TGA approved. Not PBS Listed. FDA accelerated approval 2021-05-21. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months.. (First curated: 2021-05-22)
Changed Lapatinib + Paclitaxel in Breast cancer with ERBB2 Amplification: 1B: Comments changed: TGA approved. Not PBS reimbursed. Phase 3. NCT00281658. Lapatinib + paclitaxel significantly improved OS (27.8 vs 20.5 months), PFS (9.7 vs 6.5 months), and ORR (69% vs 50%) compared to placebo + paclitaxel in HER2-positive metastatic breast cancer patients. HER2 positivity determined by FISH.TGA approved. Not PBS reimbursed. NCT00281658: HER2 positivity determined by FISH.. (First curated: 2020-05-04)
Changed Pemigatinib in Cholangiocarcinoma with FGFR2 Fusions, FGFR2-ACLY fusion, FGFR2-AFF4 fusion, FGFR2-AHCYL1 fusion, FGFR2-ARHGAP22 fusion, FGFR2-ARHGAP24 fusion, FGFR2-ATAD2 fusion, FGFR2-ATF2 fusion, FGFR2-BICC1 fusion, FGFR2-BICD1 fusion, FGFR2-CCDC158 fusion, FGFR2-CCDC170 fusion, FGFR2-CCDC6 fusion, FGFR2-CEP128 fusion, FGFR2-COL16A1 fusion, FGFR2-CTNNA3 fusion, FGFR2-DBP fusion, FGFR2-DNAJC12 fusion, FGFR2-EEA1 fusion, FGFR2-EIF4ENIF1 fusion, FGFR2-FILIP1 fusion, FGFR2-GAB2 fusion, FGFR2-GOPC fusion, FGFR2-INSC fusion, FGFR2-KCTD1 fusion, FGFR2-KIAA1217 fusion, FGFR2-KIAA1598 fusion, FGFR2-LAMC1 fusion, FGFR2-MACF1 fusion, FGFR2-MATR3 fusion, FGFR2-MCU fusion, FGFR2-NEDD4L fusion, FGFR2-NOL4 fusion, FGFR2-NRAP fusion, FGFR2-NRBF2 fusion, FGFR2-PAH fusion, FGFR2-PAWR fusion, FGFR2-POC1B fusion, FGFR2-PXN fusion, FGFR2-RABGAP1L fusion, FGFR2-RASSF4 fusion, FGFR2-RPAP3 fusion, FGFR2-SFI1 fusion, FGFR2-SHROOM3 fusion, FGFR2-SLMAP fusion, FGFR2-SOGA1 fusion, FGFR2-SPICE1 fusion, FGFR2-STRN4 fusion, FGFR2-TACC1 fusion, FGFR2-TFEC fusion, FGFR2-TRIM8 fusion, FGFR2-TTC28 fusion, FGFR2-TXLNB fusion, FGFR2-USH2A fusion, FGFR2-VCL fusion, FGFR2-WAC fusion, FGFR2-WDHD1 fusion, FGFR2-ZMYM4 fusion: 1B: Comments changed: TGA approved. Not PBS reimbused. Phase 2 FIGHT-202 trial. NCT02924376. N=146. Pemigatinib showed an objective response in 35.5% of patients with FGFR2 fusions or rearrangements, with a median follow-up of 17.8 months.TGA approved; Not PBS reimbused; FIGHT-202. (First curated: 2020-05-12)
Changed Enasidenib in Acute myeloid leukaemia with IDH2 R140Q, R140, R172K, R172S: 1B: Comments changed: TGA approved. Not PBS reimbursed. Phase 1/2 trial. NCT01915498. Enasidenib induced hematologic responses in relapsed/refractory AML patients with mutant IDH2, with an overall response rate of 40.3% and median overall survival of 9.3 months, and was generally well tolerated with grade 3 to 4 adverse events including indirect hyperbilirubinemia and IDH-inhibitor-associated differentiation syndrome.TGA approved. Not PBS reimbursed. For relapsed/refractory AML.. (First curated: 2020-05-07)
Changed Regorafenib in Gastrointestinal stromal tumour with KIT Protein expression: 1B: Comments changed: PBS reimbursed based on CD117 (c-KIT) IHC. Phase 3 GRID trial. NCT01271712. N=199. Regorafenib significantly improved PFS (4.8 months vs 0.9 months) compared to placebo in patients with metastatic GIST after failure of imatinib and sunitinib.PBS reimbursed based on CD117 (c-KIT) IHC. NCCN Category 1. (First curated: 2020-05-07)
Changed Imatinib in Myelodysplastic/myeloproliferative diseases with PDGFRA FIP1L1-PDGFRA Fusion; Fusion: 1B: Comments changed: TGA approved. Not PBS reimbursed. Multicenter prospective study. NCT00276929. Imatinib mesylate achieved complete hematologic remission in 27 FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome patients, with durable responses at 100-400 mg daily, and treatment discontinuation led to rapid reappearance of fusion transcript.. (First curated: 2020-04-16)
Changed Imatinib in Myelodysplastic/myeloproliferative diseases with PDGFRB Fusions: 1B: Comments changed: TGA approved. Not PBS reimbursed. Retrospective cohort study. N=26. Patients with myeloid malignancies bearing PDGFRB fusion genes treated with imatinib had a 10-year overall survival rate of 90% and 6-year progression-free survival rate of 88% with 96% response rate.. (First curated: 2020-04-16)
Changed Selpercatinib in Non-small cell lung cancer with RET Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion: 1B: Comments changed: TGA approved. Not PBS reimbursed. FDA Approved 21/09/2022. Phase 1-2 LIBRETTO-001 trial. NCT03157128. Selpercatinib showed an ORR of 64% in 105 previously treated RET fusion-positive NSCLC patients and 85% in 39 previously untreated patients, with durable responses and intracranial activity.TGA approved. Not PBS reimbursed. FDA Approved 21/09/2022. LIBRETTO-001: First-line treatment. ORR 85%.. (First curated: 2020-05-08)
Changed Elotuzumab + Lenalidomide + Dexamethasone in Multiple myeloma with SLAMF7 Protein expression: 1B: Comments changed: TGA approved. Not PBS reimbursed. Phase 3 ELOQUENT-2 trial. NCT01239797. N=646. Elotuzumab + lenalidomide + dexamethasone significantly improved PFS (19.4 vs 14.9 months) and ORR (79% vs 66%) compared to lenalidomide + dexamethasone alone in patients with relapsed or refractory multiple myeloma.. (First curated: 2020-06-15)
Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with Tumour Mutational Burden High: 1B: Comments changed: TGA provisionally approved. Phase 3 CHECKMATE227 trial. Nivolumab + Ipilimumab significantly improved PFS (7.2 vs 5.5 months) and ORR (45.3% vs 26.9%) compared to chemotherapy in NSCLC patients with high TMB (≥10 mut/MB). Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort but outcomes not correlated with TMB.TGA provisionally approved. Phase 3 CHECKMATE 227. Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort. Median PFS: 7.2 vs 5.5 months. Not correlated with TMB.. (First curated: 2020-11-26)
Changed Dasatinib + Blinatumomab in Acute lymphoblastic leukaemia with ABL1 BCR-ABL1 Fusion: 2: Comments changed: Phase 2 GIMEMA LAL2116 D-ALBA trial. N=63. CR rate 98%. Molecular response rate increased from 29% after dasatinib induction to 60% after 2 cycles of blinatumomab. At 18 months, OS was 95% and DFS was 88%.GIMEMA LAL2116 D-ALBA trial. CR rate 98%. OS 18 month: 95%. DFS: 88%.. (First curated: 2020-12-11)
Changed Nilotinib in Acute lymphoblastic leukaemia with ABL1 BCR-ABL1 Fusion: 2: Comments changed: Not TGA approved for ALL; Phase 1 dose-escalation study. NCT00109707. N=119. Nilotinib showed activity in imatinib-resistant CML with hematologic and cytogenetic responses observed across various disease phases, and had a relatively favorable safety profile.Not TGA approved for ALL; Positive Phase 3 study. (First curated: 2020-05-21)
Changed Dabrafenib + Trametinib in Biliary tract cancers with BRAF V600E: 2: Comments changed: Not TGA approved. Note FDA approval for tumour agnostic indication 23/06/2022. Phase 2 ROAR trial. NCT02034110. N=43. Dabrafenib plus trametinib showed activity in BRAF(V600E)-mutated biliary tract cancer with BICR ORR 47% and manageable safety profile.Not TGA approved. FDA approval for tumour agnostic indication 23/06/22. ROAR. BICR ORR 47%.. (First curated: 2020-09-21)
Changed Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF V600E: 2: Comments changed: Not TGA approved. FDA approved. Phase 3 BREAKWATER trial (NCT04607421, N=637) demonstrated that encorafenib + cetuximab + mFOLFOX6 significantly improved outcomes compared to standard of care in previously untreated BRAF V600E-mutant metastatic colorectal cancer: ORR (60.9% vs 40.0%), median duration of response (13.9 vs 11.1 months), PFS (12.8 vs 7.1 months), and OS (30.3 vs 15.1 months). Updated 2025-05-31.Not TGA approved. FDA approved. Phase 3 BREAKWATER trial. NCT04607421. Encorafenib + cetuximab + mFOLFOX6 significantly improved ORR over SOC (60.9% vs 40.0%) in previously untreated BRAF V600E-mutant metastatic colorectal cancer, with a median duration of response of 13.9 months versus 11.1 months.. References changed: 39863775, 10.1200/JCO.2025.43.16_suppl.LBA3500. (First curated: 2025-03-22)
Changed Dabrafenib + Trametinib in Glioblastoma, High-grade glioma, Low-grade glioma with BRAF V600E: 2: Comments changed: Not TGA approved. Phase 2. ROAR. NCT02034110. Dabrafenib plus trametinib showed ORR of 33% (15/45) in high-grade glioma (32% in glioblastoma) and 69% (9/13) in low-grade glioma, with a safety profile consistent with other indications.Phase 2. ROAR. ORR was 33% (15/45) In high-grade glioma (10/31, 32% in glioblastoma). ORR was 69% (9/13) in the low-grade glioma cohort.. (First curated: 2022-04-07)
Changed Rucaparib in Prostate cancer with BRCA1 Oncogenic mutations: 2: Comments changed: Not TGA Approved. Phase 2 TRITON2 study. Rucaparib showed antitumor activity in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration, with confirmed ORR of 43.5% and PSA response rate of 54.8%.Not TGA Approved. TRITON2 trial.. (First curated: 2020-05-20)
Changed Rucaparib in Prostate cancer with BRCA2 Oncogenic mutations: 2: Comments changed: Not TGA Approved. Phase 2 TRITON2 study. Rucaparib showed antitumor activity in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration, with confirmed ORR of 43.5% and PSA response rate of 54.8%.Not TGA Approved. TRITON2 trial.. (First curated: 2020-05-20)
Changed Rucaparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 2: Comments changed: Not TGA approved. NCT02855944. Phase 3 ARIEL4 trial. NCT02855944. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5.7 months) in patients with relapsed ovarian cancer and a deleterious BRCA1 or BRCA2 mutation.Not TGA approved. NCT02855944. ARIEL4. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5·7 months), including both platinum sensitive and resistant populations.. (First curated: 2022-04-09)
Changed Dacomitinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 2: Comments changed: Not TGA approved. Phase 3 ARCHER 1050 and 1009 trials. Dacomitinib showed improved PFS over gefitinib (14.7 vs 9.2 months) in first-line EGFR-mutation-positive NSCLC, but not over erlotinib in previously treated NSCLC (2.6 months in both groups).Not TGA approved. ARCHER 1009/1050. (First curated: 2020-04-27)
Changed Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR G719, L861Q, S768I: 2: Comments changed: Intermediate response to first generation EGFR TKI; G719X mutation in NSCLC has an average response rate of 35.1% to TKIs, and other uncommon EGFR mutations such as exon 18 indels, exon 19 insertions, A763_Y764insFQEA, S768I, L861Q, kinase domain duplications, and rearrangements are also responsive to EGFR TKIs.Intermediate response to 1G TKI with resistance data. (First curated: 2020-05-20)
Changed Fedratinib in Myelofibrosis with JAK2 V617F: 2: Comments changed: Not TGA approved. FDA approved. Phase 2, JAKARTA-2, NCT01523171, N=97, Fedratinib achieved a spleen response in 55% (46/83) of assessable patients with ruxolitinib-resistant or ruxolitinib-intolerant myelofibrosis, with common grade 3-4 adverse events including anaemia (38%) and thrombocytopenia (22%).. (First curated: 2020-06-15)
Changed Entrectinib, Ceritinib in Solid tumours with ALK Oncogenic mutations: 4: Comments changed: Case report of a 57-year-old male patient with ALK-rearranged inflammatory myofibroblastic tumor showing drastic responses to two ALK inhibitors, ASP3026 and ceritinib (LDK378), with serum hyaluronan levels used to monitor treatment efficacy.. (First curated: 2020-04-16)
Changed BAY2010112 in Prostate cancer with PSMA Protein expression: 4: Comments changed: Preclinical studies. Bispecific antibodies and Fab conjugates targeting PSMA and CD3 demonstrated potent and selective activity against prostate cancer cell lines, with effective T cell redirection and cytotoxicity, and induced regression of human prostate cancer xenografts in mice.. (First curated: 2020-04-16)
Changed Bispecific PSMA/CD3 antibody in Prostate cancer with PSMA Protein expression: 4: Comments changed: Preclinical study. A PSMA-targeting CD3 bispecific antibody induced antitumor responses that were enhanced by 4-1BB costimulation, leading to durable antitumor responses and T-cell memory in preclinical solid tumor models.. (First curated: 2020-04-16)
Changed Sonidegib, Vismodegib in Medulloblastoma with PTCH1 Loss-of-function mutations: 4: Comments changed: Preclinical study. RAS/MAPK activation drives resistance to Smo inhibition and enhances metastatic behavior in Shh pathway-dependent tumors, with evidence of RAS/MAPK-driven tumor evolution in Smo inhibitor-treated BCC patients.. (First curated: 2020-04-25)
Changed Olaparib in Breast cancer with CHEK2 Oncogenic mutations: R2: Comments changed: Phase 2 TBCRC 048 study. NCT not specified. N=54. Olaparib showed ORR of 33% and 31% in cohorts 1 and 2 respectively, with responses primarily observed in gPALB2 (ORR 82%) and sBRCA1/2 (ORR 50%) mutations, but not in ATM or CHEK2 mutations alone.TBCRC048. (First curated: 2020-05-30)
Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-small cell lung cancer with EGFR+RET EGFR:Oncogenic mutations and RET:fusion: R2: Comments changed: RET fusions mediate acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC, and combined EGFR and RET inhibition with osimertinib and BLU-667 shows promise as a well-tolerated and effective treatment strategy.. (First curated: 2020-10-05)
Changed Gefitinib, Erlotinib, Afatinib, Osimertinib in Non-small cell lung cancer with EGFR+ROS1 : R2: Alterations changed: EGFR:Oncogenic mutations and ROS1:fusion, GOPC-ROS1 fusion. Comments changed: Case report. GOPC-ROS1 rearrangement identified as an acquired resistance mechanism to osimertinib, with subsequent response to crizotinib combined treatments in lung adenocarcinoma patient.. (First curated: 2020-10-05)
Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-small cell lung cancer with STK11+KRAS STK11:Oncogenic mutations AND KRAS:Oncogenic mutations: R2: Comments changed: Preclinical study and retrospective observational analysis. STK11/LKB1 mutations in KRAS-mutant lung adenocarcinoma are associated with resistance to PD-1 inhibitors, resulting in lower ORR (7.4% vs 35.7% and 28.6%) and diminished PFS and OSPre-clinical study. (First curated: 2020-04-16)

21 June, 2025 (Version: 20250621AU)

New Quizartinib in Acute myeloid leukaemia with FLT3 Internal tandem duplication: 4: Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480
New Gilteritinib in Acute myeloid leukaemia with FLT3 Internal tandem duplication, D835Y, D835V, Y842C: 4: Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480
New Foretinib in Acute myeloid leukaemia with FLT3 Internal tandem duplication, F691L, D835Y, D835V, Y842C: 4: Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480
New Palbociclib in Desmoplastic small round cell tumours with WT1 EWSR1-WT1 fusion: 4: Preclinical study. Comprehensive transcriptomic analysis reveals CDK4/6 inhibitors as potential therapeutic agents for Desmoplastic Small Round Cell Tumors by targeting the cyclin D-CDK4/6-RB axis upregulated by EWSR1-WT1, with palbociclib demonstrating reduced tumor growth in xenograft models. References: 38588409
New Gilteritinib in Acute myeloid leukaemia with FLT3 F691L: R2: Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480
New Quizartinib in Acute myeloid leukaemia with FLT3 F691L, D835Y, D835V, Y842C: R2: Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations. References: 38231480
New Polatuzumab vedotin + Bendamustine + Rituximab in Diffuse large B-cell lymphoma with KLHL6 Protein expression: R2: Preclinical study. Genome-wide CRISPR-Cas9 screens in DLBCL cell lines revealed that CD79B glycosylation and KLHL6 determine sensitivity to Polatuzumab vedotin (Pola-V) by influencing epitope availability and CD79B protein levels, respectively. References: 38683128
New Idarubicin + Cytarabine in Acute myeloid leukaemia with U2AF1 S34F, Q157R: R2: Preclinical study. U2AF1 mutations in AML confer resistance to idarubicin and cytarabine by mis-splicing mRNA translation genes and activating the integrated stress response (ISR). Targeting this pathway with ISRIB resensitizes U2AF1 mutant cells to chemotherapy. References: 38417135

18 June, 2025 (Version: 20250618AU)

Changed Avapritinib in Gastrointestinal stromal tumour with PDGFRA Exon 18 mutation, D842V, D842_H845del: 2: Comments changed: Not TGA approved; FDA approved. Phase 1 NAVIGATOR trial. NCT02508532. Avapritinib showed antitumor activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumors, with an overall response rate of 88% (5 complete responses, 44 partial responses). In the first-line setting at 300 mg (RP2D), ORR was 93% (26/28) with a CBR of 100%.Not TGA approved; FDA approved. Phase 1 NAVIGATOR trial. NCT02508532. Avapritinib showed promising antitumor activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumors, with an overall response rate of 88% (5 complete responses, 44 partial responses). In the first-line setting at 300 mg (RP2D), ORR was 93% (26/28) with a CBR of 100%.. (First curated: 2020-04-27)
Changed Cadonilimab + Anlotinib in Non-small cell lung cancer with CD274 Protein expression: 3: Comments changed: Phase Ib/II trial. NCT04646330. N=69. Cadonilimab and anlotinib demonstrated manageable safety and activity with an ORR of 51% (25/49) at 15mg/kg Q3W and 60% (12/20) at 10mg/kg Q3W as first-line treatment in advanced NSCLC. ORRs differed between PD-L1-positive (60.5%) and PD-L1-negative (42.3%) patients. PD-L1 expression was assessed by immunohistochemistry using PD-L1 IHC 22C3 pharmDx (Dako Omnis), with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%. High PD-L1 expression was not required for entry into the trial.Phase Ib/II trial. NCT04646330. N=69. Cadonilimab and anlotinib demonstrated manageable safety and promising efficacy with an ORR of 51% (25/49) at 15mg/kg Q3W and 60% (12/20) at 10mg/kg Q3W as first-line treatment in advanced NSCLC. ORRs differed between PD-L1-positive (60.5%) and PD-L1-negative (42.3%) patients. PD-L1 expression was assessed by immunohistochemistry using PD-L1 IHC 22C3 pharmDx (Dako Omnis), with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%. High PD-L1 expression was not required for entry into the trial.. (First curated: 2025-04-23)
Changed Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3: Comments changed: Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.. (First curated: 2024-11-04)
Changed Izalontamab brengitecan in Non-small cell lung cancer with EGFR Oncogenic mutation and NOT Exon 19 deletion and NOT L858R, Exon 20 insertion: 3: Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 69% and mPFS of 7.0 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 69% and mPFS of 7.0 months.. (First curated: 2025-05-31)
Changed Izalontamab brengitecan in Non-small cell lung cancer with ERBB2 Oncogenic mutations: 3: Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 53%, DCR 100%, and mPFS of 7.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 53%, DCR 100%, and mPFS of 7.5 months.. (First curated: 2025-05-31)
Changed TQB2102 in Colorectal adenocarcinoma with ERBB2 Overexpression: 3: Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). (First curated: 2025-05-31)
Changed TQB2102 in Gastric cancer with ERBB2 Overexpression: 3: Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). (First curated: 2025-05-31)
Changed TQB2102 in Solid tumours with ERBB2 Overexpression: 3: Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). (First curated: 2025-05-31)
Changed TQB2102 in Breast cancer with ERBB2 Overexpression, Protein expression, Low-protein expression: 3: Comments changed: Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed promising anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%). (First curated: 2025-05-31)
Changed Sotorasib + Panitumumab in Colorectal adenocarcinoma with KRAS G12C: 3: Comments changed: Phase 1b CodeBreaK 101 trial. NCT04185883. N=40. Sotorasib + panitumumab + FOLFIRI showed efficacy in pretreated KRAS G12C-mutated mCRC with ORR of 57.5%, median PFS of 8.2 months, and median OS of 17.9 months.Phase 1b CodeBreaK 101 trial. NCT04185883. N=40. Sotorasib + panitumumab + FOLFIRI showed promising efficacy in pretreated KRAS G12C-mutated mCRC with ORR of 57.5%, median PFS of 8.2 months, and median OS of 17.9 months.. (First curated: 2025-05-31)
Changed Izalontamab brengitecan in Non-small cell lung cancer with KRAS Oncogenic mutations, G12C: 3: Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.. (First curated: 2025-05-31)
Changed Izalontamab brengitecan in Non-small cell lung cancer with MET Exon 14 deletion, Exon 14 splicing mutation,: 3: Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.. (First curated: 2025-05-31)
Changed SHR-1826 in Solid tumours with MET Overexpression, Amplification, Oncogenic mutation: 3: Comments changed: Phase 1 study. NCT06094556. N=116. SHR-1826, a c-MET-directed antibody-drug-conjugate, demonstrated a manageable safety profile and anti-cancer activity in heavily pretreated advanced solid tumors, particularly in NSCLC patients with an ORR of 40% and median PFS of 6.8 months.Phase 1 study. NCT06094556. N=116. SHR-1826, a c-MET-directed antibody-drug-conjugate, demonstrated a manageable safety profile and promising anti-cancer activity in heavily pretreated advanced solid tumors, particularly in NSCLC patients with an ORR of 40% and median PFS of 6.8 months.. (First curated: 2025-06-04)
Changed Izalontamab brengitecan in Non-small cell lung cancer with ALK Fusion: 4: Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.. (First curated: 2025-05-31)
Changed Exarafenib in Solid tumour with BRAF V600E, Class II mutations, Class III mutations: 4: Comments changed: Phase 1/1b trial. NCT04913285. Exarafenib demonstrated clinical activity and tolerability in patients with BRAF-altered solid tumors and NRAS mutant melanoma, with a ORR 18% and SD in 47% of patients.Phase 1/1b trial. NCT04913285. Exarafenib demonstrated promising clinical activity and tolerability in patients with BRAF-altered solid tumors and NRAS mutant melanoma, with a ORR 18% and SD in 47% of patients.. (First curated: 2023-05-05)
Changed Tusamitamab ravtansine in Non-small cell lung cancer with CEACAM5 Overexpression: 4: Comments changed: Phase1/2 trial. NCT02187848. SAR408701, an antibody-drug conjugate, showed antitumor activity in heavily pretreated NSQ NSCLC patients with high CEACAM5 expression, with an ORR of 20%.Phase1/2 trial. NCT02187848. SAR408701, an antibody-drug conjugate, showed promising antitumor activity in heavily pretreated NSQ NSCLC patients with high CEACAM5 expression, with an ORR of 20%.. (First curated: 2020-06-13)
Changed BNT142 in Ovarian cancer, Solid tumours with CLDN6 Protein expression: 4: Comments changed: Phase 1/2 BNT142-01 trial. NCT05262530. N=65. BNT142 showed anti-tumor activity with 7 partial responses in ovarian cancer and a disease control rate of 58% across all dose levels in CLDN6+ advanced solid tumors. CLDN6 positivity is defined as ≥ membrane positivity in 10% of cell. No clear relationship beween CLDN6 expression level versus response seen.Phase 1/2 BNT142-01 trial. NCT05262530. N=65. BNT142 showed promising anti-tumor activity with 7 partial responses in ovarian cancer and a disease control rate of 58% across all dose levels in CLDN6+ advanced solid tumors. CLDN6 positivity is defined as ≥ membrane positivity in 10% of cell. No clear relationship beween CLDN6 expression level versus response seen.. (First curated: 2025-06-01)
Changed GQ1001 in Solid tumour with ERBB2 Overexpression, Amplification: 4: Comments changed: Phase Ia study. NCT04450732. GQ1001, a HER2-targeting ADC, showed antitumor activity in HER2-positive advanced solid tumors, with 6 out of 15 evaluable subjects achieving confirmed partial response at doses ≥ 7.2 mg/kg, and a median progression-free survival of 4.8 months.Phase Ia study. NCT04450732. GQ1001, a HER2-targeting ADC, showed promising antitumor activity in HER2-positive advanced solid tumors, with 6 out of 15 evaluable subjects achieving confirmed partial response at doses ≥ 7.2 mg/kg, and a median progression-free survival of 4.8 months.. (First curated: 2025-05-28)
Changed D3S-001 in Non-small cell lung cancer with KRAS G12C: 4: Comments changed: Preclinical study. D3S-001, a GDP-bound KRAS G12C inhibitor with rapid target engagement kinetics, showed robust antitumor activity preclinically and clinical efficacy.Preclinical study. D3S-001, a GDP-bound KRAS G12C inhibitor with rapid target engagement kinetics, showed robust antitumor activity preclinically and promising clinical efficacy.. (First curated: 2025-05-04)
Changed Izalontamab brengitecan in Non-small cell lung cancer with RET Fusion: 4: Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.. (First curated: 2025-05-31)
Changed Izalontamab brengitecan in Non-small cell lung cancer with ROS1 Fusion: 4: Comments changed: Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed promising activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.. (First curated: 2025-05-31)
Changed Zolbetuximab, Zolbetuximab + Pembrolizumab in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: R2: Comments changed: Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.. (First curated: 2024-11-04)
Changed Durvalumab in Endometrial cancer with Mismatch repair Proficient, NOT Deficient: R2: Comments changed: Phase 2 trial. NCT03015129. Durvalumab showed activity in dMMR advanced endometrial carcinoma with ORR of 47% and median PFS of 8.3 months, but limited activity in pMMR advanced endometrial carcinoma with ORR of 3% and median PFS of 1.8 months.Phase 2 trial. NCT03015129. Durvalumab showed promising activity in dMMR advanced endometrial carcinoma with ORR of 47% and median PFS of 8.3 months, but limited activity in pMMR advanced endometrial carcinoma with ORR of 3% and median PFS of 1.8 months.. (First curated: 2023-07-14)

16 June, 2025 (Version: 20250616AU)

New Varegacestat in Aggressive fibromatosis with APC Loss-of-function mutations; oncogenic mutations: 3: Phase 2 RINGSIDE trial. NCT04871282. Varegacestat showed an Objective Response Rate (ORR) of 64% and Disease Control Rate (DCR) of 97% in patients with desmoid tumors, with a median best change in tumor volume of -85% and a well-tolerated safety profile at the recommended 1.2 mg QD dose. Responses were seen in both PC (43%, n=7) and CTNNB1 (68%, n=19) mutations. References: 10.1016/j.annonc.2024.08.1857, 10.1200/JCO.2025.43.16_suppl.11516
New Varegacestat in Aggressive fibromatosis with CTNNB1 T41A, S45F, Gain-of-function mutations, Oncogenic mutations: 3: Phase 2 RINGSIDE trial. NCT04871282. Varegacestat showed an Objective Response Rate (ORR) of 64% and Disease Control Rate (DCR) of 97% in patients with desmoid tumors, with a median best change in tumor volume of -85% and a well-tolerated safety profile at the recommended 1.2 mg QD dose. Responses were seen in both APC (43%, n=7) and CTNNB1 (68%, n=19) mutations. References: 10.1016/j.annonc.2024.08.1857, 10.1200/JCO.2025.43.16_suppl.11516
New LOXO-783, LOXO-783 + Fulvestrant, LOXO-783 + Letrozole, LOXO-783 + Anaztrozole, LOXO-783 + Paclitaxel in Solid tumours with PIK3CA H1047R: R2: Phase 1a/b PIKASSO-01 trial. NCT05307705. LOXO-783, a PI3Kα H1047R inhibitor, demonstrated mutant selectivity and reduced hyperglycemia, with objective response rates (ORR) and clinical benefit rates (CBR) of 3%/17% in monotherapy, 5%/19% with endocrine therapy, and 19%/25% when combined with paclitaxel, though limited by high rates of diarrhea. References: 10.1158/1557-3265.SABCS24-PS7-03
Changed Brentuximab Vedotin in Anaplastic large cell lymphoma with CD30 Protein expression: 1: Comments changed: PBS reimbursed. Phase 2 trial. N=58. Brentuximab vedotin induced objective responses in 86% of patients and CRs in 57% with relapsed/refractory systemic ALCL, with median duration of response of 12.6 months, targeting CD30-positive malignant cells.. (First curated: 2020-06-15)
Changed Brentuximab Vedotin in Cutaneous T-cell lymphoma with CD30 Protein expression: 1: Comments changed: PBS reimbursed. Phase 3 ALCANZA trial. NCT01578499. N=128. Brentuximab vedotin significantly improved objective global response lasting at least 4 months compared to physician's choice (56.3% vs 12.5%) in CD30-positive cutaneous T-cell lymphoma patients.. (First curated: 2020-06-15)
Changed Daratumumab + Bortezomib + Dexamethasone in Multiple myeloma with CD38 Overexpression: 1: Comments changed: Phase 3 trial. NCT02136134. N=498. Daratumumab + bortezomib + dexamethasone significantly improved PFS (HR, 0.39) and ORR (82.9% vs 63.2%) compared to bortezomib + dexamethasone in relapsed or refractory multiple myeloma, with higher CD38 expression associated with better response.. (First curated: 2020-06-15)
Changed Goserelin in Breast cancer with ESR1 Protein expression: 1: Comments changed: Standard of care. Randomised clinical trial. N=138 (136 eligible). Goserelin resulted in similar FFS and OS as surgical ovariectomy in premenopausal patients with ER and/or PgR-positive metastatic breast cancer.. (First curated: 2020-04-16)
Changed Medroxyprogesterone Acetate in Breast cancer with ESR1 Protein expression: 1: Comments changed: Standard of care. Randomised phase 3 trials compared the efficacy of megestrol acetate or medroxyprogesterone acetate with tamoxifen in postmenopausal women with advanced breast cancer, showing similar response rates (25-44% vs 31-35%) and median survival times (20-24 months vs 26-32 months), with some subgroup differences in response.. (First curated: 2020-04-16)
Changed Tamoxifen in Breast cancer with ESR1 Protein expression: 1: Comments changed: Standard of care. Tamoxifen showed a 32% response rate in 59 postmenopausal women with advanced breast cancer, with tumors containing estrogen receptors and those responding to previous hormonal manipulation more likely to respond (60% and 69%, respectively).. (First curated: 2020-04-16)

14 June, 2025 (Version: 20250614AU)

New Ceritinib in Non-small cell lung cancer with ALK Amplification: 4: Retrospective study. ALK-positive NSCLC. Median PFS on sequential crizotinib and ceritinib was 17.4 months, with ceritinib showing significant antitumor activity even after crizotinib treatment, and no difference in PFS on ceritinib between patients with or without ALK resistance mutations. Updated 2025-06-14. References: 25724526
New Avapritinib in Solid tumours with KIT D816V, V654A, N655K, Y672C, D677N, T670A: 4: Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation. References: 31270078
New Crizotinib in Non-small cell lung cancer with ALK C1156Y, Fusion and Amplification, L1196M, S1206Y, G1269A, T1151ins: R2: Retrospective study. ALK-positive NSCLC. Median PFS on sequential crizotinib and ceritinib was 17.4 months, with ceritinib showing significant antitumor activity even after crizotinib treatment, and no difference in PFS on ceritinib between patients with or without ALK resistance mutations. Updated 2025-06-14. References: 25724526
New Crizotinib in Non-small cell lung cancer with ALK Fusion AND Amplification, L1196M, C1156Y, F1174L, F1174V, G1202R, G1269A, I1171T, I1171S, L1152R, L1152V, T1151R, T1151M, L1198F, S1206F, D1203E: R2: Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085
New Ensartinib in Non-small cell lung cancer with EGFR Oncogenic mutations: R2: Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085
New Ensartinib in Non-small cell lung cancer with ERBB2 Oncogenic mutations: R2: Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085
New Avapritinib in Solid tumours with KIT V560D, V560D and V654A, V560D and and V670I, T670I, T670V: R2: Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation. References: 31270078
New Midostaurin in Solid tumours with KIT V654A, N655K, Y627C, D677N, T670I, T670A, T670V: R2: Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation. References: 31270078
New Ensartinib in Non-small cell lung cancer with KRAS Oncogenic mutations: R2: Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14. References: 31628085
Removed Midostaurin in Gastrointestinal stromal tumour with KIT alterations V654A, T670I: Tier R2 (First curated: 2020-05-15)
Changed Ensartinib in Non-small cell lung cancer with ALK : 4: Alterations changed: Fusion AND Amplification, L1196M, C1156Y, F1174L, F1174V, G1202R, G1269A, I1171T, I1171S, L1152R, L1152V, T1151R, T1151M, L1198F, S1206F, D1203EAmplification, protein expression. Comments changed: Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14.. References changed: 31628085, 25724526. (First curated: 2020-04-25)
Changed Therapy in Solid tumours with BRAF Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R: 4: Therapy changed: Vociprotafib + CobimetinibRMC-4630 + Cobimetinib. (First curated: 2020-11-03)
Changed Midostaurin in Solid tumours with KIT D816V, T670A, T670V: 4: Comments changed: Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation.. (First curated: 2020-06-18)
Changed Sorafenib in Thymic carcinoma with KIT : 4: Alterations changed: Exon 11 mutation, Exon 11 deletion. Comments changed: Case report. A relapsed thymic carcinoma patient with C-KIT exon 11 deletion mutation showed positive response to sorafenib.. (First curated: 2022-07-27)
Changed Bezuclastinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation, Exon 11 deletion, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829P: 4: Comments changed: Phase 1b/2a trial. NCT02401815. N=39. Combination of type I KIT inhibitor PLX9486 and type II KIT inhibitor sunitinib showed clinical benefit in patients with refractory GIST, with median PFS of 12.1 months and clinical benefit rate of 80% at the recommended phase 2 dose.. (First curated: 2023-06-27)
Changed Therapy in Thymic carcinoma with KIT Exon 11 mutation, Exon 11 deletion, V560del: 4: Therapy changed: ImatinibSorafenib. Comments changed: Case report. Thymic carcinoma with overexpressed mutated KIT showed response to imatinib.. (First curated: 2022-07-27)
Changed Imatinib in Thymic carcinoma with KIT Exon 11 mutation, Y553N: 4: Comments changed: Case report. A heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma showed an impressive response to imatinib.. (First curated: 2022-07-27)
Changed Sorafenib in Thymic carcinoma with KIT Exon 17 mutation, D820E: 4: Comments changed: Case report. A heavily pretreated patient with metastatic thymic carcinoma responded to sorafenib, with a c-kit missense mutation (D820E) on exon 17 potentially explaining the clinical response.. (First curated: 2022-07-27)
Changed Cabozantinib in Gastrointestinal stromal tumour with KIT : 4: Alterations changed: Exon 9 mutations, A502_Y503dup, Exon 11 mutations, Exon 11 deletion, K558_G565delinsR, Exon 17 mutations, D820G, V559A, V559D, V560G, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829PExon 9 mutations, A502_Y503dup, Exon 11 mutations, K558_G565delinsR, Exon 17 mutations, D820G. (First curated: 2021-08-13)
Changed Axitinib in Gastrointestinal stromal tumour with KIT L576P, V669D, V559A, V559G, T670I, V654A, N822K, A829P: 4: Comments changed: Preclinical study. Axitinib showed potent activity against various cKIT primary and secondary mutations, including imatinib-resistant T670I and V654A mutants, in GIST preclinical models and patient-derived primary cells.. (First curated: 2020-06-27)
Changed LOP628 in Solid tumours with KIT Overexpression: 4: Comments changed: Preclinical study. c-KIT-directed antibody-drug conjugate LOP628 exhibited potent antiproliferative activity against c-KIT-positive cell lines and demonstrated regressions or stasis in GIST and SCLC xenograft models, including an imatinib-resistant GIST model.. (First curated: 2020-04-16)
Changed Therapy in Solid tumours with KRAS G12: 4: Therapy changed: AvutometinibCH5126766. Comments changed: Phase 1 dose-escalation and basket dose-expansion study. NCT02407509. Avutometinib, a RAF-MEK inhibitor, demonstrated antitumour activity in RAS/RAF-mutant solid tumours and multiple myeloma, with 7 (27%) of 26 response-evaluable patients achieving objective responses at the recommended phase 2 dose of 4.0 mg twice per week.. (First curated: 2020-11-10)
Changed Therapy in Solid tumours with KRAS G12, Amplification: 4: Therapy changed: Vociprotafib + CobimetinibRMC-4630 + Cobimetinib. (First curated: 2020-11-03)
Changed Therapy in Solid tumours with NF1 Oncogenic mutations: 4: Therapy changed: Vociprotafib + CobimetinibRMC-4630 + Cobimetinib. (First curated: 2020-11-03)
Changed Therapy in Colorectal adenocarcinoma with ERBB2 ERBB2-GRB7 fusion: R2: Therapy changed: Afatinib, Trastuzumab, Cetuximab, Cetuximab + irinotecan. Comments changed: Case series. Targetable kinase alterations (RTK alterations and MAP2K1 mutations) identified in 8% of colorectal carcinoma, preferentially associated with wild-type RAS/RAF, and may predict poor response to anti-EGFR therapy.. (First curated: 2023-04-20)
Changed Afatinib, Dacomitinib, Neratinib, Pyrotinib in Solid tumours, Non-small cell lung cancer with ERBB2 Exon 20 insertion except G778ins, S779ins, P780ins: R2: Comments changed: Preclinical study. ERBB2 mutations characterized across 25 tumor types, with poziotinib showing potent activity against HER2 mutants, and enhancing T-DM1 activity in pre-clinical models, and showing 42% confirmed objective response rate in ERBB2 exon 20-mutant NSCLC patients.. (First curated: 2020-06-15)
Changed Lapatinib in Solid tumours with ERBB2 L755S, L755P, A775_G776insYVMA (Y772_A775dup), G778ins, P780_Y781insGSP (G778_P780dup), P780ins, V842I, L869R: R2: Comments changed: Preclinical study. ERBB2 mutations characterized across 25 tumor types, with poziotinib showing potent activity against HER2 mutants, and enhancing T-DM1 activity in preclinical models, with a 42% confirmed objective response rate in ERBB2 exon 20-mutant NSCLC patients in Phase 2 clinical testing.. (First curated: 2020-05-15)

13 June, 2025 (Version: 20250613AU)

New Brigatinib in Non-small cell lung cancer with ROS1 Fusions: 3: Phase 2. Barossa study. N=51. Brigatinib showed an ORR of 71% and median PFS of 12.0 months in TKI-naive NSCLC patients, and 32% ORR with 7.3 months median PFS in crizotinib-pretreated NSCLC patients. References: 39018589
New Azenosertib in Solid tumours with CCNE1 Amplification: 4: Preclinical study. Azenosertib demonstrated broad antitumor activity across solid tumors in Phase I monotherapy studies. Preclinical data revealed tumor growth inhibition >60% in CCNE1-amplified models (2/2) and FBXW7-mutated models (3/5). References: 34423975
New Azenosertib in Solid tumours with FBXW7 Oncogenic mutations: 4: Preclinical study. Azenosertib demonstrated broad antitumor activity across solid tumors in Phase I monotherapy studies. Preclinical data revealed tumor growth inhibition >60% in CCNE1-amplified models (2/2) and FBXW7-mutated models (3/5). References: 34423975
New Paclitaxel in Oesophageal squamous cell carcinoma with LGALS1 Protein expression: R2: Preclinical study. Galectin-1 is a key mediator of paclitaxel resistance in esophageal squamous cell carcinoma, acting through the interaction with β-catenin and enhancing MDR1 transcription, thereby increasing resistance to paclitaxel. References: 39186691
New Tazemetostat in Solid tumours with SMARCB1 Oncogenic mutations: R2: Phase 2 NCI-COG Pediatric MATCH trial Arm C. NCT03213665. N=20. Tazemetostat showed limited objective response (ORR 5%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but achieved prolonged stable disease in 33% of patients, suggesting potential disease stabilization. References: 10.1200/JCO.2022.40.16_suppl.10009
Removed Palbociclib in Triple-negative breast cancer with CDKN2A alterations Oncogenic mutations: Tier R2 (First curated: 2020-04-25)
Changed Obinutuzumab in Follicular lymphoma with CD20 Protein expression: 1: Comments changed: Phase 3 trial. TOWER. NCT02013167. N=405. Blinatumomab significantly improved overall survival (7.7 vs 4.0 months), remission rates (44% vs 25%), and event-free survival (31% vs 12%) in adults with relapsed or refractory B-cell precursor ALL, including both Ph-positive and Ph-negative subtypes. Note that surface antigen CD-19 is lineage-specific to B-cells and constitutively expressed on the majority of B-cell precursor ALL blasts and does not represent a biomarker selection criteria.PBS reimbursed. (First curated: 2020-06-15)
Changed Gemtuzumab Ozogamicin in Acute myeloid leukaemia with CD33 Protein expression: 1B: Comments changed: TGA approved. Not PBS reimbursed. Phase 3 AAML0531 trial (N=1022) demonstrated that gemtuzumab ozogamicin, a CD33-targeted immunoconjugate, added to chemotherapy improved event-free survival (53.1% vs 46.9%) by reducing relapse risk (32.8% vs 41.3%) in children and adolescents with de novo acute myeloid leukemia.. (First curated: 2020-06-17)
Changed Daratumumab + Hyaluronidase-fihj in Multiple myeloma with CD38 Overexpression: 2: Comments changed: Phase 3 COLUMBA trial. NCT03277105. Subcutaneous daratumumab was non-inferior to intravenous daratumumab in terms of overall response (41% vs 37%).. (First curated: 2020-06-15)
Changed BOS172738 in Medullary thyroid cancer with RET Fusions: 3: Comments changed: Phase 1 study. NCT03780517. BOS172738, a potent and selective RET inhibitor, showed an ORR of 33% in RET-altered tumors, including 33% in NSCLC and 44% in MTC (7/16, including 1 CR), with a favorable safety profile and durable responses.ORR 44% (7/16), including 1 CR. (First curated: 2021-06-05)
Changed Vandetanib in Non-small cell lung cancer with RET Fusions: 3: Comments changed: Phase 2 LURET trial. UMIN000010095. Vandetanib showed an ORR of 53% (9/17) and median PFS of 4.7 months in patients with RET-rearranged advanced NSCLC, indicating RET rearrangement as a targetable alteration.Single-arm phase 2. LURET. ORR 47%. PFS 4.7mo. References changed: 2782561627825636. (First curated: 2020-11-17)
Changed Cabozantinib in Non-small cell lung cancer with RET : 3: Alterations changed: Fusions, KIF5B-RET fusion, Rearrangement. Comments changed: Phase 2 trial. NCT01639508. N=26. Cabozantinib yielded an ORR of 28% in patients with RET-rearranged non-small-cell lung cancer, with KIF5B-RET being the predominant fusion type.Not TGA approved. Single-arm phase 2. ORR 28%. (First curated: 2020-04-27)
Changed Cabozantinib in Non-small cell lung cancer with ROS1 Fusions: 4: Comments changed: Case report. Cabozantinib showed effectiveness in treating a CD74-ROS1-positive advanced NSCLC patient for 1.5 years, and subsequent crizotinib therapy remained effective after cabozantinib resistance developed.. References changed: 32103985, NCT01639508. (First curated: 2020-06-16)
Changed Tazemetostat in Ovarian small cell carcinoma with SMARCA2 Loss-of-function mutations: 4: Comments changed: Preclinical study. Xenograft and cell line SCCOHT models deficient in SMARCA2 and SMARCA4 showed antiproliferative and antitumour effects when treated with EZH2 inhibitor tazemetostat, exemplifying an additional class of rhabdoid-like tumours dependent on EZH2 activity for survival.Xenograft and cell line SCCOHT models. Induces potent antiproliferative and antitumour effects.. (First curated: 2020-06-15)
Changed Palbociclib in Non-small cell lung cancer with SMARCA4 Loss-of-function mutations: 4: Comments changed: Preclinical study. SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in NSCLC, due to reduced cyclin D1 expression caused by restricted CCND1 chromatin accessibility and suppressed c-Jun, a transcription activator of CCND1.SMARCA4 loss is synthetic lethal with palbociclib in NSCLC cell line.. (First curated: 2021-04-14)
Changed Pembrolizumab in SMARCA4-deficient thoracic sarcoma with SMARCA4 Oncogenic mutations: 4: Comments changed: Case report. Exceptional response to pembrolizumab observed in a SMARCA4-deficient thoracic sarcoma overexpressing PD-L1, suggesting pembrolizumab as a potential treatment strategy for PD-L1-positive SMARCA4-DTS.. (First curated: 2023-01-11)
Changed BET inhibitor in Solid tumours with SMARCA4 Oncogenic mutations: 4: Comments changed: Preclinical study. Bromodomains are acetyl lysine 'reader' modules with potential anticancer activities, and BET inhibitor programmes provide insights for developing non-BET bromodomain-targeting drugs.. (First curated: 2020-04-16)
Changed Pembrolizumab, Durvalumab, Atezolizumab, Nivolumab in Pancreatic adenocarcinoma with SMARCB1 Oncogenic mutations: 4: Comments changed: Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status, with median PFS and OS of 9 and 15 months, respectively, and 2 patients having ongoing responses at 33+ and 36+ months.Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.. (First curated: 2022-02-09)
Changed Itraconazole, Arsenic trioxide in Basal cell carcinoma, Medulloblastoma with SMO D477G, E522K, G457S, S391N, D388N, N223D, L225R: 4: Comments changed: Preclinical study. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation, showing activity against tumors with acquired resistance to Smoothened antagonists, including SMO(D477G) mutant.Preclinical study. Itraconazole and arsenic trioxide block resistant SMO mutation activity in vitro.. (First curated: 2022-03-04)
Changed Posaconazole in Basal cell carcinoma with SMO Oncogenic mutations: 4: Comments changed: Preclinical study. Posaconazole inhibits Hedgehog signaling pathway by antagonizing Smoothened (SMO) with a distinct mechanism, showing robust activity against drug-resistant SMO mutants and inhibiting Hh-dependent basal cell carcinoma growth in vivo.Cell-line evidence only. (First curated: 2020-04-16)
Changed JQ1 in Solid tumours with SMO Oncogenic mutations: 4: Comments changed: Preclinical study. BET bromodomain inhibition through JQ1 effectively targets Hedgehog-driven tumors, including those with genetic lesions conferring resistance to Smoothened antagonists, by directly regulating GLI transcription.. (First curated: 2020-04-16)
Changed Everolimus in Perivascular epithelioid cell tumour with TSC1 Oncogenic mutations: 4: Comments changed: Phase 3 EXIST-2 trial. NCT00790400. Everolimus showed significant angiomyolipoma response rate of 42% (50% reduction in total volume) compared to 0% with placebo in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.. (First curated: 2022-03-20)
Changed Everolimus in Renal cell carcinoma with TSC1 Oncogenic mutations: 4: Comments changed: Mutations in MTOR, TSC1, or TSC2 were more common in responders (28%) than nonresponders (11%) to rapalogs in metastatic renal cell carcinoma, indicating a potential association between mTOR pathway gene mutations and treatment response.Drug is PBS reimbursed but not biomarker selected. (First curated: 2020-04-27)
Changed Everolimus in Perivascular epithelioid cell tumour with TSC2 Oncogenic mutations: 4: Comments changed: Phase 3 EXIST-2 trial. NCT00790400. Everolimus showed significant angiomyolipoma response rate of 42% (50% reduction in total volume) compared to 0% with placebo in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.. (First curated: 2022-03-20)
Changed Everolimus in Renal cell carcinoma with TSC2 Oncogenic mutations: 4: Comments changed: Phase 2 RECORD-3 study. NCT00903175. No significant difference in OS between first-line everolimus followed by sunitinib and first-line sunitinib followed by everolimus in metastatic RCC.No survival benefit vs Sunitinib. (First curated: 2020-06-11)
Changed Pembrolizumab in Colorectal adenocarcinoma with Tumour Mutational Burden High: 4: Comments changed: Phase 2 KEYNOTE-158 study. NCT02628067. Prospective biomarker analysis in 790 patients showed tTMB-high status (>=10 mutations per megabase) was associated with improved ORR to pembrolizumab (29% vs 6% in non-tTMB-high). However, tTMB could be a novel predictive biomarker for response to pembrolizumab in patients with advanced solid tumours, KEYNOTE-158 did not include MSS colorectal cancers.. (First curated: 2020-09-25)
Changed Toripalimab in Gastric cancer with Tumour Mutational Burden High: 4: Comments changed: Phase Ib/2 NCT02915432 trial. Toripalimab demonstrated an overall response rate of 12.1% and median overall survival of 4.8 months in chemo-refractory gastric cancer. The TMB-high group exhibited significantly superior overall survival of 14.6 months compared to 4.0 months, with an objective response rate of 33% versus 6% in the low TMB group at the 12 mutations/MB threshold.Exploratory analysis showed ORR 33 v 6% at TMB threshold of 12/MB. (First curated: 2020-11-13)
Changed Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody, immune checkpoint blockade,PD-1 targeting, immune checkpoint blockade,PD-L1 targeting in Solid tumours with Tumour Mutational Burden High: 4: Comments changed: Pan-cancer analysis of 1,662 patients treated with immune checkpoint inhibitors (ICI) showed higher tumor mutational burden (TMB) associated with improved overall survival across multiple cancer types, although TMB cutpoints varied between cancer types.. (First curated: 2020-06-08)
Changed Olaparib in Breast cancer with XRCC2 Loss-of-function mutations: 4: Comments changed: Preclinical study. Synthetic lethal screening in MCF7 cells identified sensitivity to PARG inhibitor PDD00017273 in DNA damage-response deficient cells with BRCA1, BRCA2, PALB2, FAM175A, and BARD1 deficiencies, suggesting potential for single treatment therapy in HR deficient tumours.Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273. (First curated: 2021-06-09)
Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab in Colorectal adenocarcinoma with KRAS Oncogenic mutations: R1: Comments changed: RAS mutations, including KRAS and NRAS, were associated with resistance to anti-EGFR therapy, with patients having RAS wild-type tumors showing improved PFS and OS when treated with panitumumab-FOLFOX4 or cetuximab.. (First curated: 2020-04-16)
Changed Panitumumab, Cetuximab, Cetuximab + Irinotecan, Cetuximab + FOLFIRI, FOLFOX + Panitumumab in Colorectal adenocarcinoma with NRAS Oncogenic mutations: R1: Comments changed: RAS mutations, including KRAS and NRAS, were associated with resistance to anti-EGFR therapy, with patients having RAS wild-type tumors showing improved PFS and OS when treated with panitumumab-FOLFOX4 or cetuximab.. (First curated: 2020-04-16)
Changed Larotrectinib in Solid tumours with NTRK1 F589L, A608D, G595R, G667C, G667S: R1: Comments changed: Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.. References changed: 10.1158/1538-7445.AM2016-LB-11830333516. (First curated: 2020-05-15)
Changed Entrectinib in Solid tumours with NTRK1 G595R, G667C: R1: Comments changed: Blacklisted by FDA approval. Review discussing NTRK fusion-positive cancers, detection methods, and treatment with TRK inhibitors, highlighting resistance mediated by NTRK kinase domain mutations and potential overcoming by second-generation TRK inhibitors.. (First curated: 2020-04-30)
Changed Larotrectinib in Solid tumours with NTRK2 Q596E, Q596P, G623S, F633L: R1: Comments changed: Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.. (First curated: 2020-05-15)
Changed Entrectinib in Solid tumours with NTRK3 G623R: R1: Comments changed: Blacklisted by FDA approval. Review discussing NTRK fusion-positive cancers, detection methods, and treatment with TRK inhibitors, highlighting resistance mediated by NTRK kinase domain mutations and potential overcoming by second-generation TRK inhibitors.. (First curated: 2020-04-30)
Changed Larotrectinib in Solid tumours with NTRK3 G623R, G696A, F617L, F617L, F617C, F617I: R1: Comments changed: Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.. References changed: 10.1158/1538-7445.AM2016-LB-11830333516. (First curated: 2020-05-15)
Changed LY3023414 in Endometrial cancer with AKT1 Oncogenic mutations: R2: Comments changed: Phase 2 study. NCT02684032. N=28. LY3023414 showed modest activity in patients with advanced endometrial cancer harboring PI3K pathway mutations, with ORR 16%, CBR 28%, median PFS 2.5 months, and median OS 9.2 months.N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months. (First curated: 2021-12-17)
Changed Pembrolizumab, Atezolizumab, Nivolumab, Anti-PD-1 monoclonal antibody, Anti-PD-L1 monoclonal antibody in Non-small cell lung cancer with ALK Fusion: R2: Comments changed: IMMUNOTARGET registry. Retrospective study. N=551. Patients with advanced NSCLC and oncogenic driver alterations treated with ICI monotherapy. Objective response rate (ORR) varied by driver alteration: ALK=0%, EGFR=12%, KRAS=26%, BRAF=24%. Median PFS=2.8 months, OS=13.3 months. Notable lack of response in ALK fusion group.. (First curated: 2021-03-12)
Changed Lorlatinib in Non-small cell lung cancer with ALK L1198F and C1156Y: R2: Comments changed: Targeting ALK in ALK-rearranged malignancies is limited by emergence of drug resistance, with diverse mechanisms of resistance discovered, informing development of novel therapeutic strategies to overcome resistance.. (First curated: 2020-05-27)
Changed Venetoclax in Chronic lymphocytic leukaemia with BCL2 G101V, D103Y, A113G: R2: Comments changed: Retrospective case reports, Novel BCL2 mutations, including G101V, were identified in venetoclax-resistant CLL patients, conferring resistance by reducing the affinity of BCL2 for venetoclax and providing a potential biomarker for impending clinical relapse.. (First curated: 2020-04-25)
Changed SHP099, RMC-4550 in Triple-negative breast cancer with BRAF G464V, Class II mutations: R2: Comments changed: Preclinical study. SLLIP trial. NCT03248089. N=185. BRAF alterations detected in 22 patients (12%), with 82% being non-V600 mutations, and showed varied sensitivity to SHP2 inhibition in vitro. In cell line model for Class 2 mutation showed relative resistance to SHP2 inhibitors.Cell line model for Class II mutation showed relative resistance to SHP2 inhibitors.. (First curated: 2021-02-10)
Changed Cetuximab, Panitumumab in Colorectal adenocarcinoma with BRAF G469A, G469V, L485F, L525R, L597R, T599_V600TinsT, K601E, Class II mutations: R2: Comments changed: Retrospective study. Class 2 BRAF mutants had lower ORR compared to Class 3 (8% vs 50%) to anti-EGFR therapy, with 0% ORR in third-and-later lines treatment.Retrospective study. ORR 0% in class II BRAF mutants in third-and-later lines treatment.. (First curated: 2021-04-07)
Changed Divarasib in Colorectal adenocarcinoma, Solid tumours with BRAF G469A, L597Q, L597R, V600E, K601E: R2: Comments changed: Phase 1 trial. GO42144. NCT04449874. Divarasib. Confirmed response observed in 53.4% NSCLC and 29% colorectal cancer patients with KRAS G12C mutation, with median PFS of 13.1 and 5.6 months, respectively; serial ctDNA assessment identified genomic alterations associated with response and potential acquired and treatment-emergent resistance mechanisms.Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. (First curated: 2023-08-24)
Changed Vemurafenib in Melanoma with BRAF K601E: R2: Comments changed: Case report. Lack of response to vemurafenib in melanoma carrying BRAF K601E mutation.Case report. Lack of response to melanoma. (First curated: 2021-11-16)
Changed Vemurafenib in Melanoma with BRAF L505H: R2: Comments changed: Case report. Class 2 BRAF mutation. Secondary BRAF(L505H) mutation acquired following Vemurafenib treatment, contributing to resistance in metastatic BRAF mutant melanoma patients.Case report. Secondary mutation acquired following Vemurafenib.. (First curated: 2021-02-10)
Changed Osimertinib in Non-small cell lung cancer with BRAF Oncogenic mutations, fusion: R2: Comments changed: Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy identified EGFR T790M mutation as the most common mechanism (63%), followed by less frequent mechanisms including MET amplification (5%), HER2 amplification (13%), small cell transformation (3%), and BRAF mutations.Off-target mechanism. (First curated: 2020-06-10)
Changed Palbociclib in Pancreatic adenocarcinoma, Cholangiocarcinoma, Gallbladder cancer with CDKN2A Loss-of-function mutations, Oncogenic mutations: R2: Comments changed: TAPUR Study. N=20. Palbociclib monotherapy showed no objective response or stable disease at 16 weeks in patients with pancreatic and biliary cancers with CDKN2A loss or mutation, with median PFS of 7.2 and 7.3 weeks, and median OS of 12.4 and 11.1 weeks respectively.TAPUR. N=20. ORR and DCR 0%.. References changed: 3510071410.1200/PO.19.00124. (First curated: 2020-04-25)
Changed Vismodegib, Sonidegib in Basal cell carcinoma, Medulloblastoma with SMO D477G, E522K, G457S, S391N, D388N, N223D, L225R: R2: Tier changed: R24. Comments changed: Preclinical study. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation, showing activity against tumors with acquired resistance to Smoothened antagonists, including SMO(D477G) mutant.. (First curated: 2022-03-04)

12 June, 2025 (Version: 20250612AU)

New DB-1419 in Solid tumours with CD274 Protein expression: 4: Preclinical study. DB-1419, a bifunctional B7-H3xPD-L1 antibody-drug conjugate, demonstrated potent antitumor activity against multiple tumors with favorable pharmacokinetics and safety profiles, displaying efficient cellular internalization, direct cytotoxicity, antibody-dependent cellular cytotoxicity, and bystander effects. References: 40499141
New DB-1419 in Solid tumours with CD276 Protein expression: 4: Preclinical study. DB-1419, a bifunctional B7-H3xPD-L1 antibody-drug conjugate, demonstrated potent antitumor activity against multiple tumors with favorable pharmacokinetics and safety profiles, displaying efficient cellular internalization, direct cytotoxicity, antibody-dependent cellular cytotoxicity, and bystander effects. References: 40499141
New IBI3001 in Solid tumours with CD276 Protein expression: 4: Preclinical study. IBI3001, a B7-H3/EGFR bispecific ADC, demonstrated potent cytotoxicity in cancer cells with varying B7-H3 and EGFR expression across multiple solid tumors, and showed robust tumor growth inhibition in xenograft models. Note cytotoxicties were demonstrated across all expression levels. References: 10.1158/1538-7445.AM2024-LB055
New IBI3001 in Solid tumours with EGFR Protein expression: 4: Preclinical study. IBI3001, a B7-H3/EGFR bispecific ADC, demonstrated potent cytotoxicity in cancer cells with varying B7-H3 and EGFR expression across multiple solid tumors, and showed robust tumor growth inhibition in xenograft models. Note cytotoxicties were demonstrated across all expression levels. References: 10.1158/1538-7445.AM2024-LB055
New IBI334 in Solid tumours with EGFR Protein expression: 4: Preclinical study. IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, showed enhanced EGFR signal inhibition and potent efficacy in various xenograft models, with a large therapeutic window of >200 folds, indicating potential for safe and effective treatment of EGFR-driven solid tumors. References: 10.1158/1538-7445.AM2024-LB056
New VVD-442 in Solid tumours with ERBB2 Overexpression: 4: Preclinical study. Covalent binding to C242 in the PI3K p110 alpha RBD inhibits RAS-PI3K interaction, suppressing growth of RAS mutant and HER2 over-expressing tumors without inducing hyperglycemia. References: 10.1101/2024.12.17.629001
New BI-2493, BI-2865 in Solid tumours with HRAS Oncogenic mutations, Q95H: 4: Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666
New VVD-442 in Solid tumours with KRAS G12C: 4: Preclinical study. Covalent binding to C242 in the PI3K p110 alpha RBD inhibits RAS-PI3K interaction, suppressing growth of RAS mutant and HER2 over-expressing tumors without inducing hyperglycemia. References: 10.1101/2024.12.17.629001
New ACBI3 in Solid tumours with KRAS G12S, G12A, G12C, G12V, G13C, G13D, G13V, Q61E, Q61H, Q61P, A146P, A146T, A146V: 4: Preclinical study. A single small-molecule degrader, ACBI3, was designed to target 13 of the 17 most prevalent oncogenic KRAS mutants, achieving potent and selective degradation, and inducing tumor regression in KRAS mutant xenograft mouse models. References: 39298590
New BI-2493, BI-2865 in Solid tumours with KRAS Oncogenic mutations, G12A, G12C, G12D, G12F, G12V, G12S, G13C, G13D, V14I, L19F, Q22K, D33E, Q61H, K117N, A146V, A146T: 4: Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666
New BI-2493, BI-2865 in Solid tumours with NRAS Oncogenic mutations, L95H: 4: Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666
New ACBI3 in Solid tumours with KRAS G12R, Q61L, Q61R, Q61K: R2: Preclinical study. A single small-molecule degrader, ACBI3, was designed to target 13 of the 17 most prevalent oncogenic KRAS mutants, achieving potent and selective degradation, and inducing tumor regression in KRAS mutant xenograft mouse models. References: 39298590
New BI-2493, BI-2865 in Solid tumours with KRAS G12R, Q61L, Q61R, Q61K, A59T: R2: Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models. References: 37258666
Changed Olaparib in Breast cancer with BRCA2 : 3: Alterations changed: Oncogenic mutations AND NOT Oncogenic mutations (germline). (First curated: 2020-05-30)

11 June, 2025 (Version: 20250611AU)

New Olaparib in Breast cancer with BRCA1+ERBB2 BRCA1:Oncogenic mutation and NOT ERBB2:Overexpression and NOT ERBB2:Amplification: R2: Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer. References: 21862407
New Olaparib in Ovarian cancer with BRCA1 Oncogenic mutations: 3: Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer. References: 21862407
New Olaparib in Ovarian cancer with BRCA2 Oncogenic mutations: 3: Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer. References: 21862407
Changed Olaparib in Breast cancer with BRCA1 : 3: Alterations changed: Oncogenic mutations AND NOT Oncogenic mutations (germline). (First curated: 2020-05-30)

10 June, 2025 (Version: 20250610AU)

New LY3214996 in Solid tumours with BRAF Oncogenic mutations: 4: Phase 1. NCT02857270. LY3214996, an ERK1/2 inhibitor, tumor PD inhibition in patients with advanced cancer, with tumor regression observed in 7 patients with BRAF/non-BRAF mutant cancers. References: 10.1200/JCO.2019.37.15_suppl.3001
New Ulixertinib in Solid tumours with BRAF Oncogenic mutations: 4: Phase 1 trial. NCT01781429. N=135. Ulixertinib, an ERK1/2 kinase inhibitor, showed an acceptable safety profile and early evidence of clinical activity in NRAS- and BRAF V600- and non-V600-mutant solid tumors with partial responses observed in 14% of evaluable patients. References: 29247021
New ADT-007 in Breast cancer with HRAS G12D: 4: Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells. References: 39700396
New BAY1436032 in Low-grade glioma with IDH1 R132: 4: Phase I trial. NCT02746081. BAY1436032 showed clinical activity in a subset of heavily pretreated subjects with lower grade glioma (LGG), with an objective response rate of 11% and stable disease in 43%, and a 3-month PFS rate of 0.31, while no objective responses were observed in glioblastoma, intrahepatic cholangiocarcinoma, or other tumor types. References: 33622704
New ADT-007 in Solid tumours, Pancreatic adenocarcinoma, Lung adenocarcinoma, Colon adenocarcinoma, Breast adenocarcinoma, Low-grade serous ovarian cancer, Melanoma, Gastric cancer with KRAS G12C, G12D, G12S, G12V, G13D, P121H, Amplification: 4: Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells. References: 39700396
New H231 in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: 4: Preclinical study. ADCs targeting EGFR ligand epiregulin (EREG) demonstrate antitumor activity in colorectal cancer across RAS mutation status, offering a potential alternative to conventional EGFR-targeted therapy. References: 39693606
New ATX968 in Solid tumours with Microsatellite Instability High: 4: Preclinical study. Selective inhibition of DHX9 by a small-molecule inhibitor impairs proliferation of microsatellite instable-high and mismatch repair deficient cancers in vitro and xenograft models. References: 39589774
New ATX968 in Solid tumours with Mismatch repair Deficient: 4: Preclinical study. Selective inhibition of DHX9 by a small-molecule inhibitor impairs proliferation of microsatellite instable-high and mismatch repair deficient cancers in vitro and xenograft models. References: 39589774
New ADT-007 in Breast cancer, Melanoma with NRAS Q61K: 4: Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells. References: 39700396
New Xaluritamig in Prostate cancer with STEAP1 Protein expression: 4: Phase 1 study. Xaluritamig, a STEAP1-targeted T-cell engager, showed responses (49% PSA50; 24% ORR) in patients with metastatic castration-resistant prostate cancer, with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Note relationship between STEAP1 expression and response was not prospectively assessed in this study. References: 37861461
New Olaparib in Breast cancer with BRCA1 Promoter methylation: R2: Phase 2 COMETA-Breast study. NCT03205761. Olaparib showed limited antitumor activity in pretreated advanced triple-negative breast cancer patients with BRCA1/2 promoter methylation, with an ORR of 9% and median PFS of 2 months. References: 10.1200/JCO.2023.41.16_suppl.1093
New Olaparib in Breast cancer with BRCA2 Promoter methylation: R2: Phase 2 COMETA-Breast study. NCT03205761. Olaparib showed limited antitumor activity in pretreated advanced triple-negative breast cancer patients with BRCA1/2 promoter methylation, with an ORR of 9% and median PFS of 2 months. References: 10.1200/JCO.2023.41.16_suppl.1093
New BAY1436032 in Acute myeloid leukaemia with IDH1 R132: R2: Phase 1 study. NCT03127735. N=27. BAY1436032, an IDH1 inhibitor, showed modest clinical activity in IDH1-mutant AML with an overall response rate of 15% (4/27; 1 CRp, 1 PR, 2 MLFS) and median treatment duration of 6 months among responders. References: 32733012
New BAY1436032 in Glioblastoma, Intrahepatic cholangiocarcinoma, Solid tumours except Low-grade glioma with IDH1 R132: R2: Phase I trial. NCT02746081. BAY1436032 showed clinical activity in a subset of heavily pretreated subjects with lower grade glioma (LGG), with an ORR of 11% and SD in 43%, and a 3-month PFS rate of 0.31, while no objective responses were observed in glioblastoma, intrahepatic cholangiocarcinoma, or other tumor types. References: 33622704
New Crizotinib in Non-small cell lung cancer with MET Y1230C (Y1248C): R2: Case report. MET Y1230C mutation (0.3% pre-treatment frequency) emerged as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping, co-occurring with METex14 alteration D1010H, and was detected in ctDNA at progression after 13 months of treatment. References: 27666659
New MRK003 in Triple-negative breast cancer with NOTCH2 Rearrangements: R2: Preclinical study. NOTCH1 mutations and high N1-ICD levels correlated with GSI sensitivity in TNBC and ACC, while NOTCH2 rearrangements were associated with GSI resistance in TNBC cell lines. References: 25104330
Removed RAF dimer inhibitor in Solid tumours with BRAF alterations L597, L597Q, K601, K601E: Tier 4 (First curated: 2020-04-16)
Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with MLH1 alterations Promoter methylation: Tier 4 (First curated: 2020-04-16)
Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with MSH2 alterations Promoter methylation: Tier 4 (First curated: 2020-04-16)
Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with MSH6 alterations Promoter methylation: Tier 4 (First curated: 2020-04-16)
Removed AG-270 in Solid tumours with MTAP alterations Deletion: Tier 4 (First curated: 2020-11-23)
Removed Ulixertinib; LY3214996; LTT462; Ravoxertinib in Solid tumours with NF1 alterations Oncogenic mutations: Tier 4 (First curated: 2020-04-16)
Removed NRR2Mab in Urothelial carcinoma with NOTCH2 alterations Gain-of-function mutations: Tier 4 (First curated: 2020-04-16)
Removed MRK003 + paclitaxel in Solid tumours with NOTCH2 alterations Rearrangements: Tier 4 (First curated: 2020-04-16)
Removed Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody in Solid tumours with PMS2 alterations Promoter methylation: Tier 4 (First curated: 2020-04-16)
Changed Venetoclax + Rituximab in Chronic lymphocytic leukaemia with BCL2 Overexpression: 1: Comments changed: TGA approved. Phase 3 trial. NCT02005471. N=389. Venetoclax-rituximab demonstrates significantly improved 2-year progression-free survival (85% vs 36%) compared to bendamustine-rituximab in relapsed or refractory chronic lymphocytic leukemia, with BCL2 overexpression being a characteristic of CLL cells.. (First curated: 2020-06-15)
Changed Blinatumomab in Acute lymphoblastic leukaemia with CD19 Protein expression: 1: Comments changed: Phase 3 trial. TOWER. NCT02013167. N=405. Blinatumomab significantly improved overall survival (7.7 vs 4.0 months), remission rates (44% vs 25%), and event-free survival (31% vs 12%) in adults with relapsed or refractory B-cell precursor ALL, including both Ph-positive and Ph-negative subtypes. Note that surface antigen CD-19 is lineage-specific to B-cells and constitutively expressed on the majority of B-cell precursor ALL blasts and does not represent a biomarker selection criteria.. (First curated: 2020-06-15)
Changed Therapy in Breast cancer with ERBB2 Amplification, Overexpression: 1: Therapy changed: Ado-Trastuzumab Emtansine. (First curated: 2020-04-16)
Changed Therapy in Diffuse large B-cell lymphoma with CD79B Protein expression: 1B: Therapy changed: Polatuzumab vedotin + Bendamustine + RituximabPolatuzumab vedotin-piiq + Bendamustine + Rituximab. (First curated: 2020-06-15)
Changed Trastuzumab deruxtecan in Non-small cell lung cancer, Endometrial cancer, Salivary gland cancer with ERBB2 Amplification: 3: Comments changed: Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).. (First curated: 2025-06-09)
Changed Therapy in Salivary gland cancers with ERBB2 Amplification: 3: Therapy changed: Ado-Trastuzumab Emtansine. (First curated: 2021-10-12)
Changed Therapy in Breast cancer with ERBB2 Amplification, Overexpression: 3: Therapy changed: Tucatinib + Trastuzumab EmtansineTucatinib + Ado-Trastuzumab Emtansine. (First curated: 2022-04-22)
Changed Therapy in Non-small cell lung cancer with ERBB2 Oncogenic mutations, V659E, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G778insCPG, G776delinsVC, exon 20 insertion: 3: Therapy changed: Ado-Trastuzumab Emtansine. (First curated: 2020-05-04)
Changed Therapy in Gastroesophageal junction adenocarcinoma, Gastric Cancer with ERBB2 Overexpression: 3: Therapy changed: Ado-Trastuzumab Emtansine. (First curated: 2020-07-21)
Changed Neratinib + Trastuzumab emtansine in Breast cancer with ERBB2 Overexpression, Amplification: 3: Comments changed: Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + Trastuzumab Emtansine achieved 33.3%-35.3% CNS ORR in HER2+ breast cancer brain metastases, with median OS of 20.9-30.2 months across three cohorts.Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + ado-trastuzumab emtansine achieved 33.3%-35.3% CNS ORR in HER2+ breast cancer brain metastases, with median OS of 20.9-30.2 months across three cohorts.. (First curated: 2025-01-13)
Changed RMC-4550 in Solid tumours with BRAF Class III mutations, G466V, G596R: 4: Comments changed: SHP2 inhibition by RMC-4550 is active in cancer models with class 3 BRAF mutants, NF1 loss, or KRASG12 mutations, suppressing RAS/MAPK signaling and cell growth by disrupting SOS1-mediated RAS-GTP loading.Cell line study demonstrating BRAF class III mutations are sensitive to SHP2 inhibition.. (First curated: 2022-02-04)
Changed Trastuzumab deruxtecan in Biliary tract cancer, Ovarian cancer with ERBB2 Amplification: 4: Comments changed: Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).. (First curated: 2025-06-09)
Changed Therapy in Colorectal adenocarcinoma with ERBB2 ERBB2:amplification and KRAS:G12D: 4: Therapy changed: Ado-Trastuzumab Emtansine. (First curated: 2021-03-17)
Changed Therapy in Breast cancer with ERBB2 L755S: 4: Therapy changed: Ado-Trastuzumab Emtansine, Poziotinib. (First curated: 2021-06-16)
Changed Therapy in Gastric cancer with ERBB2 MDK-ERBB2 fusion, Fusions: 4: Therapy changed: Trastuzumab, Trastuzumab EmtansineTrastuzumab, Ado-Trastuzumab Emtansine. (First curated: 2021-05-20)
Changed Therapy in Non-small cell lung cancer with ERBB2 V659E: 4: Therapy changed: Lapatinib, Afatinib, Trastuzumab EmtansineLapatinib, Afatinib, Ado-Trastuzumab Emtansine. (First curated: 2022-04-13)
Changed Therapy in Colorectal adenocarcinoma with ERBB2+KRAS ERBB2:amplification and KRAS:G12D: 4: Therapy changed: Ado-Trastuzumab Emtansine. (First curated: 2021-03-17)
Changed Crizotinib in Non-small cell lung cancer with MET : 4: Alterations changed: D1028H (D1010H)Y1230C (Y1248C). Tier changed: 4R2. Comments changed: Case report. MET Y1230C mutation (0.3% pre-treatment frequency) emerged as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping, co-occurring with METex14 alteration D1010H, and was detected in ctDNA at progression after 13 months of treatment.Case report. Pre-treatment D1010H sensitizing to crizotinib.. (First curated: 2021-01-03)
Changed AG-270 in Solid tumours with MTAP Deletion: 4: Comments changed: Phase 1 trial. NCT03435250. N=40. AG-270/S095033, a MAT2A inhibitor, achieved 2 partial responses and 5 patients with stable disease ≥16 weeks in patients with advanced MTAP-deleted malignancies. First curated: 2020-11-23. (First curated: 2025-05-27)
Changed TetMYB in Solid tumours, Adenoid cystic carcinoma, Colorectal adenocarcinoma with MYB Alteration; Overexpression: 4: Comments changed: Phase1. MYPHISMO. NCT03287427. First-in-human trial evaluating the safety and efficacy of TetMYB vaccine in combination with anti-PD-1 antibody in patients with advanced solid cancers, including colorectal and adenoid cystic carcinoma.. (First curated: 2021-05-05)
Changed BET inhibitor in Solid tumours, Liquid cancers with MYC Amplification, Oncogenic mutations: 4: Comments changed: Review of bromodomain inhibitors, a new target class for drug development, highlighting the progress of BET inhibitors in clinical trials and discussing the potential of next-wave non-BET bromodomain inhibitors in oncology and non-oncology indications.. (First curated: 2020-04-16)
Changed BET inhibitor in Solid tumours, Liquid cancers with MYCN Amplification, Oncogenic mutations: 4: Comments changed: Preclinical studies demonstrated bromodomain inhibition as a therapeutic strategy in cancer, particularly for MYCN-amplified neuroblastoma, where BET bromodomain inhibitors downregulated the MYCN transcriptional program and impaired growth, inducing apoptosis, and conferred a significant survival advantage in in vivo models.. (First curated: 2020-04-16)
Changed eFT508 in Diffuse large B-cell lymphoma with MYD88 Gain-of-function mutations: 4: Comments changed: Preclinical study. MNK1/MNK2 inhibitor demonstrated anti-proliferative effects in DLBCL cell lines, reduced pro-inflammatory cytokine production, and showed anti-tumor activity in human lymphoma xenograft models.MNK inhibitor. (First curated: 2020-04-16)
Changed MRK003 in Solid tumours with NOTCH1 Oncogenic mutations, Overexpression: 4: Comments changed: Preclinical study. NOTCH1 mutations and expression levels of HES4 are identified as biomarkers predictive of response to gamma-secretase inhibitor (GSI) in triple-negative breast cancer and adenoid cystic carcinoma.. References changed: 25104330, 24667249. (First curated: 2020-04-16)
Changed MRK003 in Glioblastoma with NOTCH2 Gain-of-function mutations: 4: Comments changed: Pre-clinical study. NOTCH pathway blockade using gamma-secretase inhibitors depleted CD133-positive glioblastoma stem cells, inhibited neurosphere growth, and prolonged survival in xenograft models.Pre-clinical evidence. (First curated: 2020-04-16)
Changed MRK003 in Non-small cell lung cancer with NOTCH3 Overexpression: 4: Comments changed: Preclinical study. Gamma-secretase inhibitor MRK-003 inhibited Notch3 signaling, reduced proliferation, and induced apoptosis in lung cancer cell lines in vitro and in vivo.Pre-clinical evidence. (First curated: 2020-04-16)
Changed Exarafenib in Melanoma with NRAS Oncogenic mutations: 4: Comments changed: Phase 1/1b. NCT04913285. N=52. Exarafenib, a pan-RAF inhibitor, demonstrated preliminary clinical activity with 18% partial response and 47% stable disease in 34 patients across all dose levels with post-baseline tumor assessment.. (First curated: 2023-05-05)
Changed FOLFIRINOX in Pancreatic adenocarcinoma with RAD51C Oncogenic mutations (germline): 4: Comments changed: Case report. A patient with metastatic pancreatic adenocarcinoma and a germline RAD51C mutation showed a remarkable response to FOLFIRINOX, a platinum-containing chemotherapy regimen.. (First curated: 2020-07-02)
Changed Rucaparib, Niraparib in Ovarian cancer with RAD51C Promoter methylation: 4: Comments changed: Preclinical study. RAD51C promoter methylation loss causes PARP inhibitor resistance in high-grade serous ovarian carcinoma PDX models, where a single unmethylated copy of RAD51C is sufficient to drive resistance.. (First curated: 2023-01-18)
Changed RMC-4550 in Solid tumours with BRAF V600E, Class I mutations, Class II mutations, G469A: R2: Comments changed: SHP2 inhibition is active in cancers driven by class 3 BRAF mutants, NF1 loss, and certain KRASG12 mutants, which remain dependent on RAS nucleotide cycling, offering a potential therapeutic strategy for these currently intractable tumors.Cell line study.. (First curated: 2022-02-04)
Changed Palbociclib in Lung squamous cell carcinoma with CDK6 Amplification: R2: Comments changed: Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.Lung-MAP S1400C, ORR 6%. (First curated: 2020-11-10)
Changed Palbociclib in Gastrointestinal stromal tumour with CDKN2A Deletion: R2: Comments changed: Phase 2. NCT01907607. In patients with advanced GIST refractory to imatinib and sunitinib with CDKN2A loss, palbociclib showed no significant clinical activity with 86% of patients having progressive disease at 4 months and ORR 0%.Phase 2. NCT01907607. ORR 0%.. (First curated: 2022-09-28)
Changed Palbociclib in Pancreatic adenocarcinoma, Biliary tract cancer with CDKN2A Deletion, Oncogenic mutations: R2: Comments changed: TAPUR study. N=22 (12 pancreatic, 10 biliary cancer). ORR 0%. Median PFS 7.2 and 7.3 weeks, and median OS 12.4 and 11.1 weeks in pancreatic and biliary cohorts respectively, with CDKN2A loss or mutation treated with palbociclib.TAPUR. N=22. ORR 0%.. (First curated: 2022-10-16)
Changed Trastuzumab deruxtecan in Colorectal adenocarcinoma, Bladder cancer with ERBB2 Amplification and NOT overexpression: R2: Comments changed: Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).. (First curated: 2025-06-09)
Changed Therapy in Colorectal adenocarcinoma with ERBB2 Amplification, Overexpression: R2: Therapy changed: Ado-Trastuzumab Emtansine + Pertuzumab. (First curated: 2021-03-17)
Changed Therapy in Solid tumours except Breast cancer, Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with ERBB2 Amplification, Overexpression: R2: Therapy changed: Ado-Trastuzumab Emtansine. (First curated: 2022-08-26)
Changed Trastuzumab in Breast cancer with ERBB2 L755S, D769Y, V842I, K753E: R2: Comments changed: Somatic HER2 mutations, such as L755S, V842I, K753I, and D769Y, are associated with resistance to certain anti-HER2 therapies, including trastuzumab and lapatinib, while others like S310F, S310Y, R678Q, D769H, or I767M show activities, and specific mutations like L755S or D769Y may have activity from neratinib or afatinib in HER2-positive breast cancer.. (First curated: 2020-10-05)
Changed Therapy in Breast cancer with ERBB2 L755S, L755P: R2: Therapy changed: Ado-Trastuzumab Emtansine, Lapatinib + Trastuzumab, Trastuzumab, Lapatinib + Capecitabine, Lapatinib + Letrozole, Lapatinib + Paclitaxel, Trastuzumab + Paclitaxel, Trastuzumab + Pertuzumab + Paclitaxel, Trastuzumab + Capecitabine. (First curated: 2020-05-15)
Changed Lapatinib in Breast cancer with ERBB2 L755S, V842I, K753E: R2: Comments changed: Somatic HER2 mutations demonstrate varied therapeutic implications: L755S, V842I, K753I, and D769Y confer resistance to trastuzumab and lapatinib; S310F, S310Y, R678Q, D769H, and I767M are associated with favorable treatment outcomes; L755S and D769Y may respond to neratinib or afatinib.. (First curated: 2020-10-05)
Changed Lapatinib in Urothelial carcinoma with ERBB2 Overexpression: R2: Comments changed: Phase 3 trial. N=232. Maintenance lapatinib did not improve PFS (4.5 vs 5.1 months) or OS (12.6 vs 12.0 months) in HER1/HER2-positive metastatic urothelial bladder cancer patients after first-line chemotherapy, including in patients strongly positive for HER1/HER2.. (First curated: 2020-11-15)
Changed Therapy in Gastric cancer with ERBB2 ZNF207-ERBB2 fusion: R2: Therapy changed: Trastuzumab, Trastuzumab EmtansineTrastuzumab, Ado-Trastuzumab Emtansine. (First curated: 2021-05-20)
Changed Pictilisib in Solid tumours with ERBB3 Q809R: R2: Comments changed: Preclinical study. Oncogenic ERBB3 mutations identified in colon and gastric cancers, with mutant ERBB3 oncogenic activity dependent on ERBB2, suggesting potential resistance to ERBB-targeting therapies unless ERBB2 is also inhibited.. (First curated: 2022-05-18)
Changed Cetuximab in Head and neck squamous cell carcinoma with ERBB4 Oncogenic mutations: R2: Comments changed: Preclinical study. Afatinib showed antitumor activity against ESCC and HNSCC cell lines with activating oncogenic EGFR and HER4 mutations, suggesting potential for targeted therapy in patients with such mutations, particularly in HNSCC where HER4 mutations are relatively frequent, indicating a possible resistance mechanism.No response in this cohort. (First curated: 2020-04-23)
Changed GnRH agonist, Aromatase Inhibitor, Letrozole, Anastrozole, Exemestane, Tamoxifen in Breast cancer with ESR1 E380Q, V392I, S463P, V534E, P535H, L536R, L536Q, Y537S, Y537N, Y537C, D538G: R2: Comments changed: Review article discusses ESR1 mutations as a mechanism for acquired endocrine resistance in ER-positive breast cancer, occurring in approximately 20% of metastatic patients treated with endocrine therapies.. (First curated: 2020-04-26)
Changed Olaparib in Pancreatic adenocarcinoma with FANCD2 Oncogenic mutations, Oncogenic mutations (germline): R2: Comments changed: Two Phase 2 studies. N=46. Olaparib monotherapy showed limited antitumor activity in patients with pancreatic cancer with DDR-GAs, with a median PFS of 5.7 months and median OS of 13.6 months, suggesting a potential therapeutic opportunity for a subset of patients with PDAC harbouring DDR genetic alterations.Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.. (First curated: 2021-03-16)
Changed Zoligratinib in Cholangiocarcinoma with FGFR2 L618F: R2: Comments changed: Preclinical and clinical study. FGFR2 extracellular domain in-frame deletions (EID) in intrahepatic cholangiocarcinoma are present in 2.8% of patients, conferring initial sensitivity to FGFR inhibitors. The L618F FGFR2 kinase domain mutation leads to acquired resistance, which can be overcome by futibatinib.. (First curated: 2022-09-28)
Changed Dovitinib in Cholangiocarcinoma with FGFR2 N549S, N549H: R2: Comments changed: Preclinical study. Comprehensive functional evaluation of 160 nonsynonymous FGFR mutations and ten fusion genes revealed varying transforming activity and sensitivity to seven FGFR TKIs, with several hotspot mutants showing relative resistance, and compound mutations affecting TKI-sensitivity.. (First curated: 2023-02-22)
Changed Infigratinib, AZD4547, Zoligratinib in Solid tumours with FGFR3 V443, V555M: R2: Comments changed: Phase 1/2 trial. BGJ398. N = 67. Patients with metastatic urothelial carcinoma bearing FGFR3 alterations. Overall response rate of 25.4% and disease control rate of 64.2% observed. Preclinical study identified gatekeeper mutation (FGFR3(V555M)) in FGFR3 as a mechanism of acquired resistance to FGFR inhibitors.. (First curated: 2020-05-22)
Changed Sotorasib in Solid tumours with KRAS V8L, G13D, V14L, K16T, A59S, Q61R, R68S, G77V, Y96D, Y96C, K117N, D119H, A146P: R2: Comments changed: Phase1/2 study. N=38. KRAS(G12C) mutant cancers treated with adagrasib or sotorasib. Putative mechanisms of resistance detected in 45% patients, including acquired KRAS alterations, bypass mechanisms, and histologic transformation to squamous-cell carcinoma. On-target resistance identified by deep mutational scanning and in vitro validated.. (First curated: 2021-06-25)
Changed Adagrasib in Solid tumours with KRAS V9F, G13D, V14L, K16T, A59S, Q61R, E62D, Y64N, R68S, M72L, G77V, H95D, H95Q, H95R, Y96D, Y96C, Q99K, K117N, D119H, A146P: R2: Comments changed: Phase 1/2 study. NCT03785249. N=38. Mechanisms of resistance to Adagrasib include acquired KRAS alterations (G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and KRAS(G12C) allele amplification) and bypass mechanisms involving MET amplification, NRAS, BRAF, MAP2K1, RET mutations, ALK, RET, BRAF, RAF1, FGFR3 fusions, and NF1, PTEN loss-of-function mutations. Histologic transformation to squamous-cell carcinoma was observed in 2 lung adenocarcinoma patients.On-target resistance identified by deep mutational scanning and in vitro validated.. (First curated: 2021-06-25)
Changed Pembrolizumab in Colorectal adenocarcinoma with KRAS+Microsatellite Instability KRAS:Oncogenic mutations AND Microsatellite Instability:High: R2: Comments changed: Phase 3 KEYNOTE-177 trial. NCT02563002. N=307. Pembrolizumab demonstrated superior progression-free survival (16.5 vs 8.2 months, HR 0.60) with reduced treatment-related adverse events (22% vs 66%) in MSI-H/dMMR metastatic colorectal cancer, with 83% of responders maintaining ongoing responses at 24 months. The KRAS subgroup did not show PFS benefit over chemotherapy.KRAS subgroup showed no PFS benefit over chemotherapy in KEYNOTE-177. (First curated: 2020-12-11)
Changed Pembrolizumab in Colorectal adenocarcinoma with KRAS+Mismatch repair KRAS:Oncogenic mutations AND Mismatch repair:deficient: R2: Comments changed: Phase 3 KEYNOTE-177 trial. NCT02563002. N=307. Pembrolizumab demonstrated superior progression-free survival (16.5 vs 8.2 months, HR 0.60) with reduced treatment-related adverse events (22% vs 66%) in MSI-H/dMMR metastatic colorectal cancer, with 83% of responders maintaining ongoing responses at 24 months. The KRAS subgroup did not show PFS benefit over chemotherapy.KRAS subgroup showed no PFS benefit over chemotherapy in KEYNOTE-177. (First curated: 2020-12-11)
Changed Duligotuzumab + FOLFIRI in Colorectal adenocarcinoma with KRAS+NRAS NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation: R2: Comments changed: Phase 2. NCT01652482. In RAS wild-type metastatic colorectal cancer, duligotuzumab plus FOLFIRI showed no improvement in PFS or OS compared with cetuximab and FOLFIRI, with a trend for lower ORR and different toxicity profiles.NCT01652482. Phase 2. In RAS wild-type metastatic colorectal cancer, there was no improvement of duligotuzumab plus FOLFIRI compared with cetuximab and FOLFIRI.. (First curated: 2021-05-18)
Changed Cetuximab in Breast cancer, Non-small cell lung cancer, Ovarian cancer with KRAS+NRAS+BRAF NOT KRAS:Oncogenic mutation and NOT NRAS:Oncogenic mutation and NOT BRAF:Oncogenic mutation: R2: Comments changed: Phase 2 TAPUR study. NCT02693535. N=49. Cetuximab showed no objective responses in breast cancer (N=10) and NSCLC (N=10), and no objective responses but 4 patients with stable disease for at least 16 weeks in ovarian cancer (N=29).NCT02693535. TAPUR. N=49 including breast, NSCLC, and ovarian cancers. ORR 0%.. (First curated: 2022-10-16)
Changed Rucaparib in Non-small cell lung cancer with Loss-of-heterozygosity score High: R2: Comments changed: Phase 2 Lung-MAP Sub-Study, S1900A. NCT03845296. N=64 (27 squamous; 37 non-squamous). Rucaparib showed limited efficacy in NSCLC patients with high genomic LOH and/or BRCA1/2 mutations, with an ORR of 7% (4% squamous; 9% non-squamous) and median PFS of 3.2 months (non-squamous) and 2.9 months (squamous). Genomic LOH does not predict activity.Phase 2 Lung-MAP Sub-Study, S1900A. ORR 7%. Genomic LOH does not predict activity.. (First curated: 2021-06-10)
Changed Dabrafenib + Trametinib, Trametinib in Colorectal adenocarcinoma with MAP2K1 F53L: R2: Comments changed: Paired pre-post treatment sequencing identified MAPK pathway alterations, including KRAS amplification, BRAF amplification, and MEK1 mutation, driving clinical acquired resistance to RAF inhibitor combinations in BRAF-mutant colorectal cancer.. (First curated: 2020-11-25)
Changed Cabozantinib in Solid tumours with MDM2 Amplification: R2: Comments changed: Preclinical study. MDM2 amplification identified as a potential mechanism of primary or acquired resistance to cabozantinib in RET-rearranged lung cancers, with MDM2 inhibitors showing effectiveness in suppressing tumor growth.Anti-RET activity. References changed: 10.1200/JCO.2016.34.15_suppl.906832083997. (First curated: 2020-11-17)
Changed Osimertinib in Non-small cell lung cancer with MET Amplification: R2: References changed: 27252416, 3793834827252416; 37938348. (First curated: 2020-03-12)
Changed Crizotinib in Non-small cell lung cancer with MET L1195V (L1213V), Y1230 (Y1248), D1228N (D1246N), D1228 (D1246), D1246 (D1228), Y1248 (Y1230), G1163 (G1181): R2: Comments changed: Evidence for Crizotinib and potential sequential use of type II MET inhibitors (cabozantinib, glesatinib, merestinib) in NSCLC patients with MET exon 14 skipping mutations after developing resistance to type I MET inhibitors.Strong evidence for Crizotinib. Capmatinib inferred. (First curated: 2020-05-15)
Changed Pembrolizumab in High-grade gliomas with Mismatch repair Deficient: R2: Comments changed: Single-agent pembrolizumab showed a DCR of 31% with no objective responses (ORR 0%) and four patients with stable disease in a prospective study of 13 recurrent high-grade gliomas with MMR protein loss.N=13. Single-agent PD-1 inhibitor showed no response in a prospective case series (ORR 0%) with 4 SD.. (First curated: 2022-06-20)
Changed Pembrolizumab in High-grade gliomas, Anaplastic astrocytoma, Glioblastoma with Mismatch repair Deficient: R2: Comments changed: Phase 2 trial. N=13. Median age 43 years. ORR 0%. DCR 31% (4 stable disease). TMB ranged 6.8-23.4 mutations/megabase. Pembrolizumab showed no apparent benefit in patients with recurrent HGG and MMR loss.N=13. ORR 0%. All patients were microsatellite stable.. (First curated: 2021-06-24)
Changed Durvalumab in Endometrial cancer with Mismatch repair Proficient, NOT Deficient: R2: Comments changed: Phase 2 trial. NCT03015129. Durvalumab showed promising activity in dMMR advanced endometrial carcinoma with ORR of 47% and median PFS of 8.3 months, but limited activity in pMMR advanced endometrial carcinoma with ORR of 3% and median PFS of 1.8 months.PHAEDRA. Phase 2. ORR in the pMMR cohort was 3% (1 of 35) with median PFS of 1.8 months.. (First curated: 2023-07-14)
Changed Pembrolizumab + Carboplatin + Pemetrexed in Non-small cell lung cancer with NRG1 Fusions: R2: Comments changed: Retrospective registry-based study. NRG1 fusion-positive lung cancers showed heterogeneity in molecular, pathological, and clinical characteristics, with low ORR to platinum-doublet chemotherapy (13%), taxane-based chemotherapy (14%), chemoimmunotherapy (0%), and single-agent immunotherapy (20%), while afatinib achieved an ORR of 25%.Retrospective registry-based study. Chemoimmunotherapy ORR 0%.. (First curated: 2021-06-08)
Changed Androgen receptor antagonist, GnRH agonist, CYP17A1 inhibitor, Enzalutamide, Apalutamide in Prostate cancer with RB1 Oncogenic mutations: R2: Comments changed: Review. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer were discussed, including restored AR signalling, AR bypass signalling, and complete AR independence, presenting new challenges for long-term disease control.. (First curated: 2020-04-26)
Changed Androgen receptor antagonist, GnRH agonist, CYP17A1 inhibitor, Enzalutamide, Apalutamide in Prostate cancer with TP53 Oncogenic mutations: R2: Comments changed: Preclinical study. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer were reviewed, including restored AR signalling, AR bypass signalling, and complete AR independence, presenting new challenges for long-term disease control.Off-target mechanism. (First curated: 2020-04-26)

09 June, 2025 (Version: 20250609AU)

New Selumetinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 1: Phase 3 KOMET trial. NCT04924608. N=145. Selumetinib significantly improved ORR (19.7% vs 5.4%) compared to placebo in adults with NF1 and symptomatic, inoperable plexiform neurofibroma. References: 10.1200/JCO.2025.43.16_suppl.3014
New Trastuzumab deruxtecan in Non-small cell lung cancer, Endometrial cancer, Salivary gland cancer with ERBB2 Amplification: 3: Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%). References: 10.1200/JCO.2025.43.16_suppl.3020
New JSKN003 in Gastroesophageal junction adenocarcinoma, Gastric Cancer, Colorectal adenocarcinoma with ERBB2 Overexpression: 3: Pooled analysis of JSKN003-101 and JSKN003-102 trials. NCT05494918, NCT05744427. N=40. JSKN003 showed activity in heavily pretreated patients with advanced HER2-overexpressing gastrointestinal tumors, with ORR of 67% and median PFS of 9.6 months. References: 10.1200/JCO.2025.43.16_suppl.3022
New GFH375 in Solid tumours, Non-small cell lung cancer, Pancreatic adenocarcinoma with KRAS G12D: 3: Phase 1/2 trial. NCT06500676. N=32. Single-agent GFH375, a KRAS G12D inhibitor that targets both GTP-bound and GDP-bound states of mutant KRASG12D protein, showed anti-tumor activity in patients with advanced solid tumors, with ORR of 27% and DCR of 86% across dose range. ORR 42% in 12 PDAC and 52% in PDAC at target dose range. References: 10.1200/JCO.2025.43.16_suppl.3013
New BC3195 in Non-small cell lung cancer with EGFR Oncogenic mutations: 4: Phase 1. NCT05957471, N=56, BC3195, an ADC targeting CDH3, showed preliminary activity in heavily pretreated patients with NSCLC, particularly in EGFR-mutant NSCLC with an ORR of 50% and mPFS > 6 months. References: 10.1200/JCO.2025.43.16_suppl.3019
New Trastuzumab deruxtecan in Biliary tract cancer, Ovarian cancer with ERBB2 Amplification: 4: Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%). References: 10.1200/JCO.2025.43.16_suppl.3020
New LY4170156 in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with FOLR1 Protein expression: 4: Phase 1a/b study. NCT06400472. LY4170156, an ADC targeting folate receptor alpha, showed a preliminary ORR of 38% (5/13) in HGSOC patients with varying FRα expression levels and prior mirvetuximab soravtansin treatment. References: 10.1200/JCO.2025.43.16_suppl.3023
New ADRX-0706 in Solid tumours with NECTIN4 Protein expression: 4: Phase 1 trial. NCT06036121. N=53. ADRX-0706, a Nectin-4 targeting antibody-drug conjugate (ADC), showed anti-tumor activity in 30 response-evaluable subjects treated at doses ≥8 mg/kg, with a confirmed complete response in a cervical cancer patient. The study reported an ORR of 17%, including 5 objective responses, and a DCR of 47%, with 9 patients experiencing stable disease. Nectin-4 expression is retrospective analysis criteria and not prospectively assessed. References: 10.1200/JCO.2025.43.16_suppl.3018
New BRY812 in Solid tumours with SLC39A6 Protein expression: 4: Phase 1 trial. NCT06038058. N=36. BRY812, an ADC targeting LIV-1, demonstrated an ORR of 24% (8/34) in breast cancer, with response rates increasing to 43% (6/14) in patients with high LIV-1 expression (PS2+). References: 10.1200/JCO.2025.43.16_suppl.3021
New BAT8008 in Solid tumours with TACSTD2 Protein expression: 4: Phase 1 study. NCT05620017. N=170. BAT8008 showed activity in advanced cervical cancer (ORR 36%, PFS 6.8 months) and oesophageal cancer (ORR 23%, PFS 5.3 months). References: 10.1200/JCO.2025.43.16_suppl.3024
New Trastuzumab deruxtecan in Colorectal adenocarcinoma, Bladder cancer with ERBB2 Amplification and NOT overexpression: R2: Phase 2 basket trial. NCT02675829. N=88. Ado-trastuzumab emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%). References: 10.1200/JCO.2025.43.16_suppl.3020
New Tazemetostat in Epithelioid sarcoma, Atypical teratoid rhabdoid tumor with EZH2 Y666N: R2: Preclinical study. Identified molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors, and developed a combination strategy using AURKB targeting to circumvent resistance. References: 38315003
New Tazemetostat in Epithelioid sarcoma, Atypical teratoid rhabdoid tumor with RB1 Deletion, Oncogenic mutations: R2: Preclinical study. Identified molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors, and developed a combination strategy using AURKB targeting to circumvent resistance. References: 38315003
Changed Mirvetuximab soravtansine in Ovarian cancer with FOLR1 : 2: Alterations changed: Protein expression. (First curated: 2022-11-16)
Changed Repotrectinib with ROS1 Fusion: 3: Cancer type(s) changed: Solid tumours (First curated: 2022-01-21)
Changed AZD9833, Elacestrant, Tamoxifen in Breast cancer with ESR1 : 4: Alterations changed: F404L, D538G and F404L, E380Q and F404L. Comments changed: Novel ESR1 F404 mutations (F404L, F404I, and F404V) were acquired in 4% of patients in the plasmaMATCH Cohort A trial (NCT03182634, N=69). These mutations confer resistance to fulvestrant when combined with preexisting activating ESR1 mutations. In cell line models, F404L demonstrates sensitivity to tamoxifen and select SERDs. These mutations may be potentially targetable by oral ERalpha degraders in clinical development.plasmaMATCH. Treatment emergent mutation causing acquired resistance at the ligand binding domain. In cell line model, F404L is sensitive to tamoxifen and select SERDs.. (First curated: 2022-06-17)
Changed Fulvestrant in Breast cancer with ESR1 : R2: Alterations changed: F404L, F404I, F404V, D538G and F404L, E380Q and F404L. Comments changed: Novel ESR1 F404 mutations (F404L, F404I, and F404V) were acquired in 4% of patients in the plasmaMATCH Cohort A trial (NCT03182634, N=69). These mutations confer resistance to fulvestrant when combined with preexisting activating ESR1 mutations. In cell line models, F404L demonstrates sensitivity to tamoxifen and select SERDs. These mutations may be potentially targetable by oral ERalpha degraders in clinical development.plasmaMATCH. Treatment emergent mutation causing acquired resistance at the ligand binding domain.. References changed: 37982575, 10.1200/JCO.2022.40.16_suppl.1009. (First curated: 2022-06-17)

06 June, 2025 (Version: 20250606AU)

New ABBV-706 in High-grade well-differentiated neuroendocrine tumour, Neuroendocrine carcinoma, Solid tumour with SEZ6 Protein expression: 3: Phase 1. NCT05599984. ABBV-706, a SEZ6-targeting antibody-drug conjugate, showed preliminary efficacy in high-grade neuroendocrine neoplasms (NENs) with an overall objective response rate of 31% (20/64) and median progression-free survival of 6.8 months. References: 10.1200/JCO.2025.43.16_suppl.105
New SHR-1826 in Solid tumours with MET Overexpression, Amplification, Oncogenic mutation: 3: Phase 1 study. NCT06094556. N=116. SHR-1826, a c-MET-directed antibody-drug-conjugate, demonstrated a manageable safety profile and promising anti-cancer activity in heavily pretreated advanced solid tumors, particularly in NSCLC patients with an ORR of 40% and median PFS of 6.8 months. References: 10.1200/JCO.2025.43.16_suppl.106
New Sevabertinib in Non-small cell lung cancer with EGFR Exon 20 insertions, C797S: 4: Phase 1. NCT05099172. BAY2927088 is an oral TKI targeting EGFR and HER2 mutations that demonstrates strong potency and high selectivity for mutant versus wild-type EGFR, showing activities in NSCLC patients with EGFR exon 20 insertion mutations and EGFR C797S acquired resistance mutation. References: 10.1158/1538-7445.AM2023-CT126
New Sevabertinib in Non-small cell lung cancer with ERBB2 Exon 20 insertion mutation, A775_G776insYVMA (Y772_A775dup), G776delinsVC, S310F, S335C, L755S: 4: Preclinical study. BAY 2927088 showed strong antiproliferative activity against various HER2 mutations, including exon 20 insertion mutations (A775insYVMA, G776delinsVC) and point mutations (S310F, S335C, L755S), in isogenic Ba/F3 cell lines and patient-derived xenograft models. References: 10.1158/1538-7445.AM2023-4035
New DM002 in Solid tumours with MUC1 Protein expression: 4: Preclinical study. DM002 is a bispecific antibody-drug conjugate targeting HER3 and the juxtamembrane domain of MUC1, demonstrating endocytic and anti-tumor activity in patient-derived xenograft models of lung, breast, gastric, and pancreatic cancers. References: 10.1158/1538-7445.AM2023-LB214
Changed Sevabertinib in Non-small cell lung cancer with ERBB2 : 3: Alterations changed: Exon 20 insertion, Oncogenic mutations. (First curated: 2024-07-03)
Changed NVL-655 in Solid tumours, Non-small cell lung cancer with ALK : 4: Alterations changed: G1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletionG1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion. (First curated: 2025-04-30)