History of database changes

16 March, 2025 (Version: 20250316AU) (Latest version)

New AZD9592 in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 4

Preclinical study. EGFR-cMET bispecific ADC showed antitumour activities in NSCLC and head and neck squamous cell carcinoma PDX models, with responses observed across a range of dose levels. Note activities are seen in with or without EGFR mutations in NSCLC as well as in head and neck squamous cell carcinoma. References: 10.1158/1538-7445.AM2023-5736

New Everolimus + Exemestane in Breast cancer with EIF4EBP1 Protein expression: 4

Exploratory biomarker study. NCT02444390. SAFIRTOR. p4EBP1 staining was associated with treatment outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane, with high-p4EBP1 associated with higher CBR (62% vs 40%) and longer PFS (9.2 vs 5.8 months). Positive staining was defined as p4EBP1 staining with Allred score >=6. References: 38182687

New Sotorasib + Tipifarnib in Solid tumours, Non-small cell lung cancer with KRAS G12C: 4

Preclinical study. Tipifarnib and sotorasib combination showed synergistic anticancer effects in lung adenocarcinoma cells by inhibiting proliferation and interfering with HRAS activation and RHEB/lamin farnesylation. References: 38278976

New Capivasertib + Docetaxel in Prostate cancer with PTEN Loss-of-function mutations: 4

Preclinical study. Capivasertib combined with docetaxel demonstrated enhanced anti-tumor activity in prostate cancer models by inhibiting AKT-mediated survival mechanisms, particularly in PTEN-null cells. References: 38396173

15 March, 2025 (Version: 20250315AU)

New PF-9363 in Breast cancer with KAT6A Amplification, Overexpression: 4

Preclinical study. The selective KAT6A/KAT6B inhibitor demonstrated anti-tumor activity and growth suppression in KAT6-high ER+/luminal breast cancer models with or without ESR1 mutations associated with endocrine resistance. References: 37557181

New PF-9363 in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression, ESR1:D538, ESR1:Y537: 4

Preclinical study. The selective KAT6A/KAT6B inhibitor demonstrated anti-tumor activity and growth suppression in KAT6-high ER+/luminal breast cancer models with or without ESR1 mutations associated with endocrine resistance. References: 37557181

07 March, 2025 (Version: 20250307AU)

New Cabozantinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

Phase 2 trial. NCT02101736. N=19. Cabozantinib showed partial response in 42% of patients with neurofibromatosis type 1-related plexiform neurofibromas, with median change in tumor volume of 15.2%. References: 33442015

New Avutometinib + BI-3406 in Melanoma with NF1 Oncogenic mutations: 4

Preclinical study. Concurrent SOS1 and MEK inhibition suppressed signaling and growth of NF1-null melanoma, abrogated ERK activation, induced cell death, and suppressed tumor growth. References: 39488215

New Abemaciclib + LY3214996 in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 4

Preclinical study. Combined CDK4/6 and ERK1/2 inhibition enhanced antitumor activity in NF1-associated plexiform neurofibroma, with abemaciclib and LY3214996 synergizing to suppress MAPK activation and exhibiting enhanced antitumor activity in mouse models. References: 37406085

06 March, 2025 (Version: 20250306AU)

New ALTA-2618 in Breast cancer, Endometrial cancer with AKT1 E17K: 4

Preclinical study. The mutant-selective inhibitor of AKT1 E17K induced tumor regressions in multiple PDX models of breast and endometrial cancer models. References: 10.1158/1538-7445.AM2024-LB173

02 March, 2025 (Version: 20250302AU)

New AZD1390 + GSK126 in Mesothelioma with BAP1 Loss of protein expression, Oncogenic mutations: 4

Preclinical study. Combination of EZH2 and ATM inhibition showed synergistic potential against BAP1-deficient mesothelioma in drug screen and xenograft experiments, indicating a potential novel treatment modality using BAP1 as a biomarker. References: 38519707

New Talazoparib in Myelodysplastic syndrome with SRSF2 P95H, Oncogenic mutations: 4

Preclinical study. Pathogenic SRSF2 activating mutations elevate protein poly-ADP-ribosylation levels, making mutant cells more vulnerable to PARP inhibitors in Srsf2 P95H knock-in murine hematopoietic cell and MLL-AF9 leukemia models. References: 38806724

New Cetuximab in Colorectal adenocarcinoma with ARID1A Oncogenic mutations: R2

Retrospective and correlative studies. ARID1A mutations confer intrinsic and acquired resistance to cetuximab treatment in colorectal cancer. Worse treatment outcome observed in patients with ARID1A mutations treated with cetuximab-containing therapies. References: 36117191

New Methotrexate in Acute lymphoblastic leukaemia with DHFR Amplification: R2

N=67, ALL patients, DHFR gene amplification (31%) correlated with p53 mutations (P < .001) is a mechanism of acquired resistance to methotrexate. References: 7605998

New Nivolumab + FLOX in Colorectal adenocarcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: R2

Randomized Phase 2. METIMMOX trial. NCT03388190. N=80. In microsatellite stable disease, no PFS advantage was observed with alternating FLOX + nivolumab over FLOX alone (both 9.2 months). References: 38664577

24 February, 2025 (Version: 20250224AU)

New Tuvusertib in Solid tumours with ARID1A Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with ATRX Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with BRCA1 Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with BRCA2 Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New Tuvusertib in Solid tumours with DAXX Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

New IMC-F106C in Melanoma with HLA-A2+PRAME HLA-A2:A*02:01 AND PRAME:Protein expression: 4

Phase 1 trial. NCT04262466. In 31 evaluable patients, IMC-F106C, a bispecific PRAME x CD3 ImmTAC showed activity in post-checkpoint cutaneous melanoma patients with 61% CBR and 13% ORR, enriched in PRAME-positive patients (immunohistochemistry H score>1). References: 10.1200/JCO.2024.42.16_suppl.9507

New Tuvusertib in Solid tumours with TP53 Oncogenic mutation: 4

Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2. References: 38407317

22 February, 2025 (Version: 20250222AU)

New Avutometinib + Defactinib in Non-small cell lung cancer with KRAS KRAS:Oncogenic mutations + CDH1:Protein expression + VIM:NOT Protein expresssion: 4

Preclinical study. Epithelial phenotype cells with KRAS-mutated non-small cell lung cancer show an enhanced apoptotic response to avutometinib and defactinib combination therapy through Bim upregulation, but not mesenchymal phenotypes. This study also suggests that EMT status could be a potential predictive biomarker. References: 38822146

New Larotrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, F589L, V573M, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib, Zurletrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, V573M, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib in Solid tumours with NTRK2 ETV6-NTRK2 fusion, V689M: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, F617L, G623E, G696A: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, G623E: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Zurletrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, G623E, G696A: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib, Zurletrectinib in Solid tumours with NTRK1 F589L, G595R, G667A, G667C, G667S: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK1 F589L, G595R, G667A, G667C, G667S, V573M: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK1 G595R, G667A, G667C, G667S: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib in Solid tumours with NTRK2 F633L, G639R, G709C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK3 F617L, G623R, G623E, G696A, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib in Solid tumours with NTRK3 F617L, G623R, G696A, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Zurletrectinib in Solid tumours with NTRK3 F617L, G623R, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK3 G623R, G623E, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

Changed Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600: 2

References changed: 37733309, 10.1200/JCO.2022.40.17_suppl.LBA200210.1056/NEJMoa2303815, 10.1200/JCO.2022.40.17_suppl.LBA2002. (First curated: 2021-06-20)

Changed Vorasidenib in Low-grade gliomas with IDH1 Oncogenic mutation: 2

References changed: 3727251610.1056/NEJMoa2304194. (First curated: 2023-06-05)

Changed Vorasidenib in Low-grade glioma with IDH2 Oncogenic mutation: 2

References changed: 3727251610.1056/NEJMoa2304194. (First curated: 2023-06-05)

21 February, 2025 (Version: 20250221AU)

New SP2509 in Non-small cell lung cancer with DNMT3A Oncogenic mutations, Deletions, Truncating mutations, Loss-of-function mutations: 4

Preclinical study. KDM1A is a synthetic lethal partner of DNMT3A deletion in non-small cell lung cancer, reducing viability of DNMT3A-deficient cells through apoptosis. References: 38951697

New Isotretinoin + Navitoclax in Neuroblastoma with MYC Amplification: 4

Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models. References: 38942989

New Isotretinoin + Navitoclax in Neuroblastoma with MYCN Amplification: 4

Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models. References: 38942989

New Carboplatin + Etoposide, Cisplatin + Etoposide in Gastrointestinal neuroendocrine carcinoma with BRAF V600: R2

Retrospective analysis. N=229. BRAF alterations were not associated with response to platinum etoposide in gastrointestinal high-grade neuroendocrine neoplasms. References: 38909137

17 February, 2025 (Version: 20250217AU)

New Rucaparib + VE-821, Rucaparib + PF-477736, Rucaparib + MK-1775 in Ovarian cancer with BRCA1+BRCA2 NOT BRCA1:Oncogenic mutations and NOT BRCA2:Oncogenic mutations: 4

Preclinical study. ATR, CHK1, and WEE1 inhibitors induce homologous recombination repair deficiency in HR-proficient ovarian ascites models, sensitizing these cells to PARP inhibitors such as rucaparib. References: 38965423

16 February, 2025 (Version: 20250216AU)

New Odronextamab in Follicular lymphoma with CD20 Protein expression: 3

Phase II ELM-2 trial. NCT03888105. N=128. Odronextamab achieved an ORR of 80% and CR rate of 73.4%, with a median DoR of 25.1 months, PFS of 20.7 months, and OS not reached in patients with relapsed or refractory follicular lymphoma. Note of level of CD20 expression was not associated with responses irrespective at baseline, CRs seen in no or low proportions of CD20-positive cells. References: 39147364

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 4

Retrospective analysis of the Phase 2 GOZILA trial. N=702. Putative germline BRCA1/2 mutation associated with better ORR (63.2% vs 16.2%) and PFS (HR 0.55) on platinum-containing chemotherapy. References: 39198618

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 4

Retrospective analysis of the Phase 2 GOZILA trial. N=702. Putative germline BRCA1/2 mutation associated with better ORR (63.2% vs 16.2%) and PFS (HR 0.55) on platinum-containing chemotherapy. References: 39198618

New Nivolumab in Hepatocellular carcinoma with CD274 Protein expression: 4

Phase 1/2. CheckMate 040 trial. N=234 (80 sorafenib-naive, 154 sorafenib-experienced). ORR was 20% and 14% in sorafenib-naive and sorafenib-experienced groups, respectively. Median OS were 26.6 months and 15.1 months, respectively. Higher ORR and extended OS were observed with baseline PD-L1 ≥1% vs <1%, more pronounced in the sorafenib-experienced group. References: 38151184

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA2 Reversion mutations: R2

Retrospective analysis of the Phase 2 GOZILA trial. N=702. Reversion mutation of BRCA2 gene was identified in two patients. References: 39198618

New Palbociclib, Ribociclib, Abemaciclib in Breast cancer with CDK4 Amplification: R2

Retrospective analysis. N=926. Focal CDK4 amplification, identified in ER+/HER2- metastatic breast cancers, represents a candidate acquired resistance mechanism to CDK4/6 inhibitors, with higher prevalence seen in populations pretreated with CDK4/6 inhibitors. References: 39090361

New Capivasertib in Gastric cancer with ARID1A Oncogenic mutation: 4

Preclinical study. AKT inhibition showed synthetic lethality in ARID1A-deficient gastric cancer cells via pyroptosis induction through Caspase-3/GSDME pathway activation. References: 39003371

New Trastuzumab in Extramammary Paget’s disease with ERBB2+PTEN ERBB2:Oncogenic mutations and PTEN:Loss of protein expression, ERBB2:Oncogenic mutations and PTEN:Loss-of-function mutations, ERBB2:Oncogenic mutations and PTEN:Oncogenic mutations, ERBB2:Oncogenic mutations and PTEN:Deletion: R2

Preclinical study. In PDX models, trastuzumab-resistant EMPD model showed PTEN loss as a resistance mechanism. References: 38987365

New Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA1 Oncogenic mutations: 4

Phase Ib. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response. References: 38971950

New Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA2 Oncogenic mutations: 4

Phase Ib. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response. References: 38971950

14 February, 2025 (Version: 20250214AU)

Changed Repotrectinib in Non-small cell lung cancer with ROS1 Fusion: 2

Comments changed: Not TGA approved. FDA approved. Phase 2 NCT03093116. TRIDENT-1 trial. N=296. Repotrectinib showed durable clinical activity in ROS1 TKI-naïve (ORR=88%) and -pretreated pts with or without BL CNS mets, including intracranial responses.. (First curated: 2023-11-17)

10 February, 2025 (Version: 20250210AU)

New MDNA11 in Solid tumours with Microsatellite Instability High: 4

Phase 1/2 ABILITY-1 trial. NCT05086692. N=30. MDNA11 showed single-agent activity in advanced solid tumors, with ORR of 7.7% and CBR of 19.2% in 26 evaluable patients, including one confirmed PR in a PDAC (MSI-H) patient. References: 10.1158/1538-7445.AM2024-CT259

09 February, 2025 (Version: 20250209AU)

New VRN101099 in Breast cancer with ERBB2 Overexpression, Amplification: 4

Preclinical study. VRN101099, a brain-permeable HER2 kinase inhibitor, showed anti-tumor activity in HER2-positive cancer models with nanomolar potency. References: 10.1158/1538-7445.SABCS22-P1-11-03

07 February, 2025 (Version: 20250207AU)

Changed Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2 Overexpression: 2

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. Trastuzumab deruxtecan demonstrated an overall response rate (ORR) of 34% (42/122) across two dose groups. The ORR was higher in the HER2 IHC 3+ population (47%, 30/64) but lower in the HER2 IHC 2+ with amplified group (5.6%, 1/18).. (First curated: 2024-08-29)

Changed Zenocutuzumab in Solid tumours with NRG1 CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion: 2

Comments changed: Not TGA approved. FDA approved (accelerated). Phase 2 trial. NCT02912949. Updated results from phase 1/2 eNRGy trial. N=204. Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, with an ORR of 30% and median duration of response of 11.1 months; median PFS was 6.8 months. Response in PDAC was 42% in PDAC and 29% in NSCLC.Not TGA approved. FDA approved (accelerated). Updated results from phase 1/2 eNRGy trial. N=110. ORR 34% (27/84), including 42% in PDAC and 35% in NSCLC. Median DOR 9.1 months.. References changed: 39908431, 10.1200/JCO.2022.40.16_suppl.105. (First curated: 2022-06-15)

06 February, 2025 (Version: 20250206AU)

New Pemigatinib in Urothelial carcinoma with FGFR3 Fusion, R248C, S249C, S764fs*6, G370C, S371C, Y373C: 3

Phase 2. FIGHT-201. NCT02872714. N=260. Pemigatinib showed ORR of 17.8% and 23.3% in cohorts A-CD and A-ID respectively, with median DOR of 6.2 months, PFS of 4.0/4.3 months, and OS of 6.8/8.9 months in FGFR3-altered metastatic or surgically unresectable urothelial carcinoma. References: 37956738

New Erdafitinib in Urothelial carcinoma with FGFR3 S249C, Y373C, R248C, G370C, R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusion: 3

Phase 3. THOR trial. NCT03390504. N=351. Erdafitinib did not improve OS over pembrolizumab (10.9 vs 11.1 months) in anti-PD-L1-naive patients with metastatic urothelial cancer and selected FGFR alterations, but had a higher ORR (40% vs 21.6%) and longer PFS (4.4 vs 2.7 months). References: 37871702

New BBO-10203 in Breast cancer with ERBB2 Amplification, Overexpression: 4

Preclinical study. BBO-10203 demonstrates reduction of RAS-driven PI3Ka activity while maintaining normal glucose metabolism, exhibiting potent signaling pathway inhibition at low nanomolar concentrations and showing activity in PIK3CA-mutant and HER2-amplified human xenograft models. References: 10.1158/1538-7445.SABCS23-RF02-02

New Capmatinib in Non-small cell lung cancer with MET CD74-MET fusion: 4

Case report: Complete response in patient with metastatic NSCLC harboring CD47-MET fusion treated with capmatinib, achieving 18-month ongoing complete metabolic response after 3 prior lines of therapy. References: 38832711

New Olaparib in Breast cancer with BRCA1 Reversion mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Olaparib in Breast cancer with BRCA2 Reversion mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Pemigatinib in Urothelial carcinoma with FGFR3 V553M, V555L, V555M, M528I, N540S, N540K: R2

Phase 2. FIGHT-201. NCT02872714. N=260. Secondary acquired on-target resistance mutations detected at end of treatment in 6 patients. References: 37956738

New Olaparib in Breast cancer with PAXIP1 Oncogenic mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Olaparib in Breast cancer with RIF1 Oncogenic mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

New Olaparib in Breast cancer with TP53BP1 Oncogenic mutations: R2

Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer. References: 38244928

Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 1

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%.TGA approved. Not PBS reimbursed. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%.. (First curated: 2022-01-28)

Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 1

Tier changed: 1B. Comments changed: TGA approved. PBS reimbursed. Phase 3 trial. IMCgp100-202. NCT03070392. HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Median OS was significantly longer in tebentafusp group compared to control (21.6 versus 16.9 months). ORR was 14% (Control 5%).TGA approved. Not PBS reimbursed. Phase 3 trial. IMCgp100-202. NCT03070392. HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Median OS was significantly longer in tebentafusp group compared to control (21.6 versus 16.9 months). ORR was 14% (Control 5%).. (First curated: 2023-10-29)

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification; Overexpression: 1B

Comments changed: TGA approved. FDA approved. Phase 2 trial NCT03248492 (N=184). DESTINY-Breast01: In patients with prior anti-HER2 therapies, the objective response rate (ORR) was 62%, with a median duration of response (DOR) of 14.8 months. The median overall survival (OS) was 29.1 months, with a median progression-free survival (PFS) of 19.4 months in patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab emtansine. HER2 positivity was defined as IHC 3+ or FISH positive.TGA approved. FDA approved. DESTINY-Breast01: In patients with prior anti-HER2 therapies, median DOR 14.8mo, PFS 16.4mo. HER2 positivity: defined as IHC 3+ or FISH positive.. References changed: 31825192, 38092229. (First curated: 2020-05-12)

04 February, 2025 (Version: 20250204AU)

New GSK_WRN4 in Solid tumours with Microsatellite Instability High: 4

Preclinical study. Novel WRN helicase inhibitors selectively targeted microsatellite unstable cancer cells by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage, with activities confirmed in immunotherapy-resistant organoids and patient-derived xenograft models. References: 38587317

03 February, 2025 (Version: 20250203AU)

New Patritumab deruxtecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861Q, G719: 3

Phase 1. U31402-A-U102 trial. N=102. In EGFR-mutated NSCLC patients who progressed after EGFR TKI and platinum-based chemotherapy, Patritumab deruxtecan showed confirmed ORR of 41% and median OS 16.2 months. References: 38369013

New Patritumab deruxtecan in Non-small cell lung cancer with ERBB3 Truncating mutations, Y789fs: R2

Phase 1. U31402-A-U102 trial. N=102. In EGFR-mutated NSCLC patients who progressed after EGFR TKI and platinum-based chemotherapy, Patritumab deruxtecan showed confirmed ORR of 41% and median OS 16.2 months. References: 38369013

New Patritumab deruxtecan in Non-small cell lung cancer with TOP1 L721R: R2

References: 38369013

20 January, 2025 (Version: 20250120AU)

New Avelumab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 4

Phase 2. MITO END-3 trial. NCT03503786. N=125. Compared with chemotherapy alone, avelumab efficacy varied by molecular profiling with favorable PFS in MSI-H and worst in MSS/TP53 mut in first-line endometrial cancer therapy. Significant interactions in PFS were observed in patients with ARID1A and PTEN mutations. References: 38704093

New Avelumab + Carboplatin + Paclitaxel in Endometrial cancer with ARID1A Oncogenic mutations: 4

Phase 2. MITO END-3 trial. NCT03503786. N=125. Compared with chemotherapy alone, avelumab efficacy varied by molecular profiling with favorable PFS in MSI-H and worst in MSS/TP53 mut in first-line endometrial cancer therapy. Significant interactions in PFS were observed in patients with ARID1A and PTEN mutations. References: 38704093

19 January, 2025 (Version: 20250119AU)

New Camizestrant in Breast cancer with ESR1 E380Q, S463P, V422del, L536P, L536H, Y537C, Y537D, Y537N, Y537S, D538G: 3

Phase I. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44). References: 38729567

New Camizestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Phase I. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44). References: 38729567

New Durvalumab, Ipilimumab + Nivolumab, Nivolumab, Pembrolizumab in Colorectal cancer with POLD1 D402N, L606M: 3

Retrospective study. N=27. POLE/POLD1 proofreading-deficient metastatic CRC patients treated with immune checkpoint inhibitors showed ORR of 89%. Entry has been curated and tierd based on evidence of activity as demonstrated by the ORR, prolonged PFS, despite the absence of a prospective trial. References: 38777726

New Durvalumab, Ipilimumab + Nivolumab, Nivolumab, Pembrolizumab in Colorectal cancer with POLE P286R, S297Y, S297F, F367S, V411L, L424I, P436R, S459F, A456P: 3

Retrospective study. N=27. POLE/POLD1 proofreading-deficient metastatic CRC patients treated with immune checkpoint inhibitors showed ORR of 89%. Entry has been curated and tierd based on evidence of activity as demonstrated by the ORR, prolonged PFS, despite the absence of a prospective trial. References: 38777726

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

Comments changed: Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. The dual primary endpoint of OS at 24 months was 83% with dostarlimab and 59% with placebo, and was significantly improved over placebo with a hazard ratio of 0.69 at the updated analysis.Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. OS at 24 months was 83% with dostarlimab and 59% with placebo.. References changed: 36972026, 38866180. (First curated: 2023-12-16)

13 January, 2025 (Version: 20250113AU)

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

Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + ado-trastuzumab emtansine achieved 33.3%-35.3% CNS ORR in HER2+ breast cancer brain metastases, with median OS of 20.9-30.2 months across three cohorts. References: 38977064

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations: 1

Comments changed: TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012.. References changed: 31562799, 39284381. (First curated: 2020-04-25)

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations: 1

Comments changed: TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012.. References changed: 31562799, 39284381. (First curated: 2020-04-25)

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with Homologous Recombination Deficiency Score High: 1

Tier changed: 12. Comments changed: TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012: HRD was determined using myChoice HRD test with cut-off score of 42-100. Note: the HR proficient group also derives benefits from Niraparib.In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.Biomarker not approved by TGA. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012: HRD was determined using myChoice HRD test with cut-off score of 42-100. Note: the HR proficient group also derives benefits from Niraparib.. References changed: 31562799, 39284381. (First curated: 2020-05-04)

12 January, 2025 (Version: 20250112AU)

New Mirvetuximab soravtansine in Ovarian cancer with FOLR1 Protein expression, Overexpression: 3

Phase 2. PICCOLO trial. NCT05041257. N=79. Mirvetuximab soravtansine showed ORR of 51.9% and median DOR of 8.25 months in FRalpha-positive, third-line or later, recurrent platinum-sensitive ovarian cancer. Positive FRα expression was defined as 75% of cells with 2+ staining intensity, assessed using the VENTANA FOLR1 RxDx Assay on either a fresh/recent biopsy or archival tumour tissue. References: 39617145

New Ipilimumab + Nivolumab in Prostate cancer with Microsatellite Instability High: 3

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Mismatch repair Deficient: 3

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months. References: 39293514

New BMS-986365 in Prostate cancer with AR L702H, L702H and H875Y, L702H and T878A, L702H and W742C and T878A, T878A, W742C and T878A: 4

Phase 1. CC-94676-PCA-001. NCT04428788. In patients with progressive mCRPC, BMS-986365 showed activity in heavily pretreated patients and overcome resistance to current ARPIs, regardless of AR LBD mutation status. References: 39293515

New Ipilimumab + Nivolumab in Prostate cancer with BRCA2 Oncogenic mutation: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with CDK12 Oncogenic mutation: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Microsatellite Instability Tumour Mutational Burden:High and NOT Microsatellite instability:high: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Mismatch repair Tumour Mutational Burden:High and NOT Mismatch repair:deficient: R2

Phase II INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB. References: 39293514

Changed Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Cisplatin + Paclitaxel, Pembrolizumab + Carboplatin + Paclitaxel in Cervical cancer with CD274 Protein expression: 1

Tier changed: 12. Comments changed: TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (2021-10-13). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup. Final analysis showed that the HR of OS results was significantly different in subgroups with or without bevacizumab: 77.1 months (pembrolizumab) versus 61.4 months (control) with bevacizumab, and 53.1 months (pembrolizumab) versus 33.7 months (control) without bevacizumab.Not TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (2021-10-13). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup.. References changed: 34534429, 39393777. (First curated: 2021-09-19)

Changed Pembrolizumab in Colorectal adenocarcinoma with Mismatch repair Deficient: 1

Comments changed: PBS listed. TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. With an effective crossover rate of 62%, median OS was 77.5 v 36.7 months with chemotherapy (HR=0.73). MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.PBS listed. TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.. References changed: 33264544, 39631622, 10.1200/JCO.2020.38.18_suppl.LBA433264544, 10.1200/JCO.2020.38.18_suppl.LBA4. (First curated: 2020-12-11)

09 January, 2025 (Version: 20250109AU)

New Futibatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, E7090 in Cholangiocarcinoma with FGFR2 K642I: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Pemigatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 K660N: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550H, N550K, E566A, E566G, L618M, L618V: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550K, N550D, K660M: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Pemigatinib, Erdafitinib, E7090 in Cholangiocarcinoma with FGFR2 V563L, E566A, E566G, K642R: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 V565I: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Futibatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565F: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Infigratinib, Erdafitinib, Zoligratinib in Cholangiocarcinoma with FGFR2 K642I: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Infigratinib in Cholangiocarcinoma with FGFR2 K660N: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Infigratinib, Erdafitinib in Cholangiocarcinoma with FGFR2 N550H, N550K, E566A, E566G, L618M, L618V: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib,Infigratinib, Erdafitinib, E7090, Zoligratinib in Cholangiocarcinoma with FGFR2 N550K, N550D, K660M: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Infigratinib, Zoligratinib in Cholangiocarcinoma with FGFR2 V563L, E566A, E566G, K642R: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Derazantinib, Zoligratinib, AZD4547, Futibatinib in Cholangiocarcinoma with FGFR2 V565I: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Derazantinib, Zoligratinib, AZD4547, Futibatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 V565L: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550, L552F, V565, E566A, L618V, N653S: R2

Phase 1/2 FOENIX study. N=300. Futibatinib biomarker analysis detected treatment-emergent kinase mutation variants within 6 weeks of radiologic progression. CDKN2B alteration associated with reduced PFS in cholangiocarcinoma. References: 39672383

New Disitamab vedotin + Toripalimab in Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 3

Phase 1b/2 RC48-C014 trial. N=41. In locally advanced or metastatic urothelial carcinoma patients, disitamab vedotin + toripalimab showed confirmed ORR of 73%, median PFS of 9.3 months, and median OS of 33.1 months. The study was HER2-unselected, and responders were seen in HER2 1+/2+/3+ populations. References: 39662628

Changed Therapy in Solid tumours with FGFR1 Fusion: 4

Therapy changed: ZoligratinibDebio1347. (First curated: 2020-06-11)

Changed Therapy in Cholangiocarcinoma with FGFR2 Extracellular domain deletion, H167_N173del, L618F: 4

Therapy changed: ZoligratinibDebio1347. Comments changed: Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Zoligratinib experienced treatment response.Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Debio1347 experienced treatment response.. (First curated: 2022-09-28)

Changed Therapy in Solid tumours with FGFR2 Truncating mutations, Rearrangements, FGFR2-E18, FGFR2-delE18, Exon 18 truncating mutations, FGFR2-BICC1 fusion, FGFR2-ATE1 fusion, FGFR2-E18-C2, FGFR2-E18-C3, FGFR2-E18-C4, Y674*, Y678*, L681fs*, P686*, S687fs*, S694*, C287R, Splice mutations, FGFR2-I17, FGFR2-E1-17AND Amplification: 4

Therapy changed: AZD4547, Pemigatinib, ZoligratinibAZD4547, Pemigatinib, Debio1347. (First curated: 2024-11-22)

Changed Therapy in Solid tumours with FGFR1 V561M: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347. (First curated: 2020-05-22)

Changed Therapy in Cholangiocarcinoma with FGFR2 L618F: R2

Therapy changed: ZoligratinibDebio1347. (First curated: 2022-09-28)

Changed Therapy in Solid tumours with FGFR2 V565I, N550K, V564M, V564F: R2

Therapy changed: Infigratinib, AZD4547, Zoligratinib, Dovitinib, PonatinibInfigratinib, AZD4547, Debio1347, Dovitinib, Ponatinib. (First curated: 2020-05-22)

Changed Therapy in Cholangiocarcinoma with FGFR3 N540K, V555M, L608V: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347. (First curated: 2023-02-22)

Changed Therapy in Solid tumours with FGFR3 V443, V555M: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347. (First curated: 2020-05-22)

06 December, 2024 (Version: 20241206AU)

New Revumenib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Mixed phenotype acute leukaemia with KMT2A Rearrangement: 2

FDA approved. Not TGA approved. Phase 1/2. AUGMENT-101 trial. NCT04065399. N=94. Revumenib led to high remission rates with 23% of complete remission rate and 63% ORR in relapsed/refractory KMT2Ar acute leukaemia. References: 39121437

New Revumenib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia with KMT2A Rearrangement: 3

Phase 1. NCT04065399. Revumenib showed low frequency of grade 3 or higher treatment-related adverse events and 30% rate of complete remission or complete remission with partial haematologic recovery in patients with relapsed or refractory acute leukaemia. References: 36922593

New Zenocutuzumab in Solid tumours with NRG1 Fusion, CD74-NRG1 fusion, CLU-NRG1 fusion, ATP1B1-NRG1 fusion, SLC3A2-NRG1 fusion, APP-NRG1 fusion: 4

N=3. 2/3 patients with NRG1 fusion-positive metastatic cancer achieved rapid responses, including 2 with ATP1B1-NRG1 pancreatic cancer and 1 with CD74-NRG1 non-small cell lung cancer. References: 35135829

Changed Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression: 2

Comments changed: Not TGA approved. FDA approved (accelerated). Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months.Not TGA approved. FDA approved. Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months.. (First curated: 2023-06-04)

Changed Zenocutuzumab in Solid tumours with NRG1 CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion: 2

Tier changed: 23. Comments changed: Not TGA approved. FDA approved (accelerated). Updated results from phase 1/2 eNRGy trial. N=110. ORR 34% (27/84), including 42% in PDAC and 35% in NSCLC. Median DOR 9.1 months.. (First curated: 2022-06-15)

04 December, 2024 (Version: 20241204AU)

Changed Belzutifan in Hemangioblastoma with VHL Oncogenic mutations (germline): 1

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved. Phase 2. NCT03401788. LITESPARK-004. Updated results. Belzutifan showed antitumor activity in VHL-associated renal cell carcinoma and other neoplasms. Updated results from CNS hemangioblastomas ORR 44%, DCR 90%, time 5.4 months, median PFS was not reached.TGA approved. Not PBS reimbursed. FDA approved. Phase 2. NCT03401788. LITESPARK-004. Updated results. Belzutifan showed antitumor activity in VHL-associated renal cell carcinoma and other neoplasms. Updated results from CNS hemangioblastomas ORR 44%, DCR 90%, time 5.4 months, median PFS was not reached.. (First curated: 2023-07-24)

Changed Belzutifan in Pancreatic neuroendocrine tumour, Hemangioblastoma with VHL Oncogenic mutations (germline): 1

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas.TGA approved. Not PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas.. (First curated: 2021-12-02)

Changed Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline): 1

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%.TGA approved. Not PBS listed. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%.. (First curated: 2021-09-15)

02 December, 2024 (Version: 20241202AU)

New Trastuzumab in Breast cancer with ERBB2 p95 expression: R2

Preclinical study. HER2-overexpressing breast cancer cells expressing p95HER2 were resistant to trastuzumab, but sensitive to lapatinib, with significant growth inhibition and tumor regression in xenograft models. References: 17440164

New Lapatinib in Breast cancer with ERBB2 p95 expression: 4

Preclinical study. HER2-overexpressing breast cancer cells expressing p95HER2 were resistant to trastuzumab, but sensitive to lapatinib, with significant growth inhibition and tumor regression in xenograft models. References: 17440164

22 November, 2024 (Version: 20241122AU)

New BWA-522 in Prostate cancer with AR AR-FL; AR-V7: 4

Preclinical study. Orally bioavailable PROTAC degrader targeting N-terminal domain of androgen receptor inducing degradation of both AR-FL and AR-V7 in prostate cancer cell line and rowth inhibition in LNCaP xenograft model. References: 37556600

New CC-94676 in Prostate cancer with AR Wildtype, Amplifications, Oncogenic mutations: 4

Phase 1. NCT04428788. in metastatic castration-resistant prostate cancer patients, CC-94676 34% of patients achieved PSA30 across all dose levels. References: 10.1200/JCO.2024.42.4_suppl.134

New AZD4547, Pemigatinib, Debio1347 in Solid tumours with FGFR2 Truncating mutations, Rearrangements, FGFR2-E18, FGFR2-delE18, Exon 18 truncating mutations, FGFR2-BICC1 fusion, FGFR2-ATE1 fusion, FGFR2-E18-C2, FGFR2-E18-C3, FGFR2-E18-C4, Y674*, Y678*, L681fs*, P686*, S687fs*, S694*, C287R, Splice mutations, FGFR2-I17, FGFR2-E1-17AND Amplification: 4

Preclinical study. Truncated FGFR2 identified as actionable oncogene in multiple cancers, including rearrangements, partial amplifications, and nonsense/frameshift mutations, with FGFR2-E18 truncation being a single-driver alteration. References: 35948633

Changed Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression: 2

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months.. (First curated: 2023-06-04)

Changed Bemarituzumab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with FGFR2 : 4

Alterations changed: Overexpression, FGFR2b:Overexpression, FGFR2-IIIb:Overexpression. (First curated: 2022-11-01)

Changed Bemarituzumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with FGFR2 : 4

Alterations changed: Overexpression, FGFR2b:Overexpression, FGFR2-IIIb:Overexpression, amplification. (First curated: 2020-06-26)

13 November, 2024 (Version: 20241113AU)

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with BRCA1 Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with BRCA2 Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with PALB2 Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with RAD51C Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with RAD51D Oncogenic mutations: 4

Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer). References: 10.1200/JCO.2024.42.16_suppl.3154

05 November, 2024 (Version: 20241105AU)

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

Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma. References: 37490286

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

Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma. References: 37490286

04 November, 2024 (Version: 20241104AU)

New Gefitinib in Non-small cell lung cancer with CRKL Amplification: R2

Preclinical study. CRKL amplification induces transformation and EGFR inhibitor resistance, activates SOS1-RAS-RAF-ERK and SRC-C3G-RAP1 pathways in NSCLC lines. References: 22586683

New Atezolizumab in Hepatocellular carcinoma with CRKL Amplification, Overexpression: R2

Preclinical study. CRKL overexpression attenuates anti-PD-1 efficacy by mobilizing tumor-associated neutrophils in HCC. Blocking CRKL/β-catenin/VEGF alpha and CXCL1 axis using bevacizumab or lenvatinib overcomes anti-PD-1 resistance. References: 38403027

01 November, 2024 (Version: 20241101AU)

New Trastuzumab duocarmazine in Breast cancer with ERBB2 Overexpression, Amplification: 2

Phase 3. TULIP. NCT03262935. N=437. Trastuzumab duocarmazine improved PFS over physician's choice (7.0 vs 4.9 months) with HR of 0.64 in patients with HER2-positive advanced or metastatic breast cancer who progressed during/after 2 or more HER2-targeted therapies or after T-DM1. References: 39442070

24 October, 2024 (Version: 20241024AU)

New Palbociclib in Peritoneal mucinous carcinomatosis with GNAS Oncogenic mutations: 3

Phase 2. N=16. Palbociclib showed clinical activity in GNAS-mutant peritoneal mucinous carcinomatosis. SD was observed in 50% of evaluable patients after 12 months. Median OS was not reached at a median follow-up of 17.6 months. References: 39413348

19 October, 2024 (Version: 20241019AU)

New Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18+ERBB2 CLDN18:Protein expression AND NOT ERBB2:Overexpression; CLDN18:Protein expression AND NOT ERBB2:Amplification: 2

Phase 3. SPOTLIGHT. NCT03504397. N=565. Addition of Zolbetuximab significantly prolonged both PFS and OS in previously untreated patients with Claudin 18.2 positive and HER2 negative gastric and gastroesophageal cancers (median PFS 10.6 vs 8.7 months, median OS 18.2 vs 15.5 months). CLDN18 positive was defined as moderate-to-strong IHC staining in >= 75% of tumour cells. References: 37068504, 10.1200/JCO.2023.41.3_suppl.LBA292

New Zolbetuximab + CAPOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18+ERBB2 CLDN18:Protein expression AND NOT ERBB2:Overexpression; CLDN18:Protein expression AND NOT ERBB2:Amplification: 2

Not TGA approved. FDA approved. Phase 3 GLOW trial. NCT03653507. N=507. Zolbetuximab + CAPOX improved PFS over placebo (8.2 vs 6.8 months) and OS 14.4 vs 12.2 months in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. Claudin18.2 expression was defined as >= 75% of tumor cells with moderate-to-strong membranous staining on immunohistochemistry. References: 37524953

Removed Zolbetuximab + FOLFOX in Gastric cancer; Gastroesophageal junction adenocarcinoma with CLDN18 alterations Protein expression: Tier 2   (First curated: 2023-01-20)

13 October, 2024 (Version: 20241013AU)

New Inavolisib in Breast cancer with ESR1+ERBB2+PIK3CA ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and PIK3CA:Oncogenic mutations: 2

Not TGA approved. FDA approved. Phase 3. INAVO120 trial. NCT04191499. N=325. Inavolisib + palbociclib + fulvestrant significantly improved PFS2 (24.0 vs 15.1 months) and Time to first chemotherapy (not estimable vs 15.0 months) over placebo in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer. References: 10.1200/JCO.2024.42.16_suppl.1003

08 October, 2024 (Version: 20241008AU)

New Ribociclib + Letrozole, Ribociclib + Anastrozole, Ribociclib + Tamoxifen, Letrozole, Ribociclib + Letrozole + Goserelin, Ribociclib + Anastrozole + Goserelin, Ribociclib + Tamoxifen + Goserelin, Letrozole, Fulvestrant in Breast cancer with ESR1 D351Y, E380Q, S463P, M528I, L536H, L536P, Y537C, Y537S, Y537D, D538G: R2

Combined biomarker analysis of MONALEESA-2, -3, and -7 trials. Higher prevalences of ESR1 gene alterations was seen in D538, Y537, E380, L536 (with potential candidates at D351, M528). References: 39313156

New Ribociclib in Breast cancer with RB1 Oncogenic mutation: R2

Pooled analysis of the MONALEESA study. Significantly more alterations in the RB1 and SPEN genes at the point of progression compared to baseline in patients from the ribociclib arm. References: 39313156

New Ribociclib in Breast cancer with SPEN Oncogenic mutation: R2

Pooled analysis of the MONALEESA study. Significantly more alterations in the RB1 and SPEN genes at the point of progression compared to baseline in patients from the ribociclib arm. References: 39313156

05 October, 2024 (Version: 20241005AU)

New Gilteritinib in Acute myeloid leukaemia with ABL1 BCR-ABL1 Fusion: R2

Secondary FLT3-F691L gatekeeper mutations or BCR-ABL1 fusions were identified at progression to Gilteritinib. References: 31088841

New Gilteritinib in Acute myeloid leukaemia with FLT3 F691L: R2

Secondary FLT3-F691L gatekeeper mutations or BCR-ABL1 fusions were identified at progression to Gilteritinib. References: 31088841

04 October, 2024 (Version: 20241004AU)

New AMG 193 in Solid tumours with MTAP Deletion, Loss of protein expression: 3

Phase 1. NCT05094336. In patients with MTAP-deleted solid tumors, the MTA-cooperative PRMT5 inhibitor AMG 193 showed ORR of 21% across dose ranges of 800 mg o.d., 1200 mg o.d., or 600 mg b.i.d.. Responses were seen in cholangiocarcinoma, oesophageal carcinoma, gallbladder adenocarcinoma, melanoma, non-small cell lung carcinoma, pancreatic adenocarcinoma, renal cell carcinoma, Sertoli-Leydig cell tumor. References: 39293516

New ZN-1041 in Breast cancer with ERBB2 Overexpression, amplification: 4

Phase 1, ZN-A-1041-101-US (NCT05593094). N=10. 1 pt achieved confirmed PR at 400 mg BID dose for >15 months. References: 10.1200/JCO.2023.41.16_suppl.1041

New Trametinib + Hydroxychloroquine, Trametinib + Palbociclib in Pancreatic adenocarcinoma with KRAS Oncogenic mutation: 4

Retrospective multicentric cohort study, AIO AIO-TF/PAK-0123, N=34, trametinib + hydroxychloroquine (THCQ) or trametinib + palbociclib (TP) did not show clinical benefit in advanced metastatic pancreatic cancer with KRAS mutations or MAPK/CDKN2A/B alterations. References: 39352477

New MYTX-011 in Non-small cell lung cancer with MET Protein expression: 4

Phase 1. MYTX-011 showed improved payload delivery to c-MET-expressing tumor cells, with increased cytotoxicity and efficacy in NSCLC xenograft models. References: 38684230

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+KRAS BRAF:V600E AND KRAS:Oncogenic mutations, BRAF:V600E AND KRAS:G12, BRAF:V600E AND KRAS:G13, BRAF:V600E AND KRAS:Q61, BRAF:V600E AND KRAS:K117, BRAF:V600E AND KRAS:A146: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+MAP2K1 BRAF:V600E AND MAP2K1:Oncogenic mutations, BRAF:V600E AND MAP2K1:F53, BRAF:V600E AND MAP2K1:K57: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+MET BRAF:V600E AND MET:amplification: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

New Encorafenib + Binimetinib + Cetuximab, Encorafenib + Cetuximab in Colorectal adenocarcinoma with BRAF+NRAS BRAF:V600E AND NRAS:Oncogenic mutations, BRAF:V600E AND NRAS:G12, BRAF:V600E AND NRAS:G13, BRAF:V600E AND NRAS:Q61: R2

Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment. References: 39313594

30 September, 2024 (Version: 20240930AU)

New Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R: 4

References: 33632773

New Afatinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, G719A, G719S, S768I, L861R, L861Q, A763_Y764insFQEA: 4

References: 33632773

New Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861R, L861Q, A763_Y764insFQEA, P772_H773insGNP, A767_V769dup: 4

References: 33632773

New Mobocertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861R, L861Q, A763_Y764insFQEA, P772_H773insGNP, A767_V769dup, T790M, G719A, G719S, S768I, Exon 20 insertion, N771_H773dup, S768_D770dup: 4

Preclinical study. Mobocertinib (TAK-788) demonstrated potent inhibition of EGFR exon 20 insertion mutants in non-small cell lung cancer with selectivity over wild-type EGFR. References: 33632773

New Erlotinib, Gefitinib, Osimertinib, Mobocertinib in Non-small cell lung cancer with EGFR L858R and T790M and C797S: R2

References: 33632773

New Afatinib in Non-small cell lung cancer with EGFR T790M, Exon 20 insertion, P772_H773insGNP, A767_V769dup, N771_H773dup, S768_D770dup: R2

Intermediate sensitivities for Afatinib: S768I. References: 33632773

New Osimertinib in Non-small cell lung cancer with EGFR T790M, G719A, G719S, S768I, Exon 20 insertion, N771_H773dup, S768_D770dup: R2

References: 33632773

New Erlotinib, Gefitinib in Non-small cell lung cancer with EGFR T790M, G719A, G719S, S768I, L861R, L861Q, A763_Y764insFQEA, Exon 20 insertion, P772_H773insGNP, A767_V769dup, N771_H773dup, S768_D770dup: R2

Intermediate sensitivities for Erlotinib: G719A, L861R, L861Q, A763_Y764insFQEA. References: 33632773

25 September, 2024 (Version: 20240925AU)

New GSK2256098 in Meningioma with NF2 Oncogenic mutations: 3

Phase 2 Alliance A071401 trial. NCT02523014. N=36. GSK2256098 showed activity in NF2-mutated meningiomas, meeting PFS6 endpoint with rates of 83% (grade 1) and 33% (grade 2/3), and one partial response was observed. References: 36288512

New Lirafugratinib in Cholangiocarcinoma with FGFR2 FGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M: 4

References: 37270847

New Infigratinib in Cholangiocarcinoma with FGFR2 K310R, M537I, K641N, K659M: 4

References: 37270847

New Futibatinib in Cholangiocarcinoma with FGFR2 K310R, M537I, N549D, N549K, N549H, V564I, E565A, L617V, K641N, K659M: 4

References: 37270847

New Erdafitinib in Cholangiocarcinoma with FGFR2 K310R, M537I, N549H, V564I, E565A, L617V, K641N, K659M: 4

References: 37270847

New Pemigatinib in Cholangiocarcinoma with FGFR2 K310R, M537I, N549H, V564I, K641N, K659M: 4

References: 37270847

New RMC-9805 in Pancreatic adenocarcinoma, Non-small cell lung cancer with KRAS G12D: 4

Preclinical study. RMC-9805, a mutant-selective covalent oral KRASG12D inhibitor, induced apoptosis and tumor regression in KRASG12D models, with objective responses seen in pancreatic and non-small cell lung cancer PDX and CDX models. References: 10.1158/1538-7445.AM2023-526

New IAG933 in Solid tumours with NF2 Oncogenic mutations: 4

Preclinical study. The direct disruptor of YAP-TEAD interface showed anti-tumor activity in Hippo-driven mesothelioma xenografts and extended to larger tumor indications, including lung, pancreatic, and colorectal cancer, with durable responses. References: 38565920

New Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer with FGFR1 Amplification: R2

Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers. References: 35304457

New Futibatinib in Cholangiocarcinoma with FGFR2 V564F, V564L: R2

References: 37270847

New Infigratinib in Cholangiocarcinoma with FGFR2 V564F, V564L, N549D, N549H, N549K, E565A, V564I, L617V: R2

References: 37270847

New Pemigatinib in Cholangiocarcinoma with FGFR2 V564F, V564L, N549D, N549K, E565A, L617V: R2

References: 37270847

New Erdafitinib in Cholangiocarcinoma with FGFR2 V564F, V564L, N549K, N549D: R2

References: 37270847

New Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer with MET Amplification: R2

Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers. References: 35304457

New Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer with RET Y806C, G810C, G801S: R2

Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers. References: 35304457

Changed Lapatinib + Trastuzumab in Colorectal adenocarcinoma with ERBB2 Amplification: 3

Comments changed: Phase 2 HERACLES trial. N=27. Trastuzumab + lapatinib achieved ORR of 30% (8/27) with 1 complete response and 7 partial responses in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer.. (First curated: 2020-05-04)

Changed Therapy in Cholangiocarcinoma with FGFR2 Fusion: 3

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

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

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

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

Comments changed: Phase 2 trial. NCT01877083. N=25. Lenvatinib demonstrated an ORR of 16% and a median PFS of 7.3 months in patients with RET fusion-positive lung adenocarcinoma.Single-arm phase 2. ORR 16%. PFS 7.3mo. (First curated: 2020-11-17)

Changed Therapy in Solid tumours with FGFR2 Fusion: 4

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

Changed MRTX1133 with KRAS G12D: 4

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

Changed Selpercatinib in Lung adenocarcinoma, Medullary thyroid cancer: R2

Biomarker changed: BRAFRET. Alterations changed: D594N, Oncogenic mutationsY806C, G810C, G801S. Comments changed: Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers.. (First curated: 2022-08-07)

Changed Pictilisib + Paclitaxel in Breast cancer with PIK3CA Oncogenic mutations: R2

Comments changed: Phase 2 PEGGY trial. NCT01740336. N=183. Pictilisib did not improve PFS over placebo (8.2 vs 7.8 months) or response rate in combination with paclitaxel for hormone receptor-positive, HER2-negative breast cancer.PEGGY. No PFS improvement over placebo. Similar ORR. (First curated: 2020-11-15)

Changed MK2206 in Colorectal adenocarcinoma with PIK3CA Oncogenic mutations: R2

Comments changed: Phase 2 trial. NCT01802320. Biomarker-enriched, previously treated metastatic colorectal cancer patients received MK2206, an oral AKT inhibitor, with no radiographic responses, median PFS of 1.8 months, and median OS of 6.8 months. ORR was 0% in patients with PIK3CA mutations (0/2).ORR 0%. (First curated: 2020-07-30)

Changed Everolimus in Glioblastoma with PTEN Deletion, Loss of protein expression: R2

Comments changed: Preclinical study. Glioblastoma orthotopic xenograft test panel. PTEN loss did not predict response to everolimus with only 1 of 7 PTEN-disrupted lines showing sensitivity.. (First curated: 2024-04-30)

Changed MK2206 in Colorectal adenocarcinoma with PTEN Loss of protein expression: R2

Comments changed: Phase 2 trial. NCT01802320. Biomarker-enriched, previously treated metastatic colorectal cancer patients received MK2206, an oral AKT inhibitor, with no radiographic responses, median PFS of 1.8 months, and median OS of 6.8 months. ORR was 0% in PTEN loss patients (0/9).ORR 0%. (First curated: 2020-07-30)

Changed Vismodegib in Medulloblastoma with SMO D473, E518: R2

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

Changed Selinexor in Chronic myelogenous leukaemia, Acute lymphoblastic leukaemia, Acute promyelocytic leukaemia with XPO1 C528S: R2

Comments changed: Preclinical study. Heterozygous C528S mutation in XPO1 confers similar resistance to selinexor as homozygous substitution, demonstrating a single dominant mutation is sufficient for SINE resistance.. (First curated: 2021-06-08)

22 September, 2024 (Version: 20240922AU)

New SGN-PDL1V in Solid tumours, Head and neck squamous cell carcinoma, Non-small cell lung carcinoma with CD274 Protein expression: 4

Phase 1. SGNPDL1V-001. NCT05208762. N=55. Single agent SGN-PDL1V showed ORR of 27% (13% confirmed) and median duration of confirmed responses of 7.9 months. Responses were seen across PD-L1 levels. References: 10.1016/j.annonc.2024.08.674

New YL201 in Solid tumours, Small-cell lung cancer, Nasopharyngeal carcinoma, Non-small cell lung cancer with CD276 Protein expression: 3

Phase 1. NCT06057922 and NCT05434234. In patients with advanced solid tumors, single agent YL201 aided ORR was 74% in SCLC, 46% in NPC, and 32% in NSCLC (wild type especially in adenocarinoma and LELC); at ≥2.0 mg/kg dose level. References: 10.1016/j.annonc.2024.08.672

New SHR-A1904 in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3

Phase 1. NCT04877717. SHR-A1904 showed anti-tumor activity in 73 patients with GC/GEJC, with ORR of 56% at 6.0 mg/kg (DCR 89%). Claudin 18.2 positivity in ≥ 1% of cells. References: 10.1016/j.annonc.2024.08.676

New DS-9606a in Solid tumours, Testicular cancer, Gastric cancer, Non-small cell lung cancer with CLDN6 Protein expression: 4

Phase 1. NCT05394675. N=40. In Phase 1 DS-9606a trial, confirmed responses were seen in in germ-cell tumours, gastric cancer, and non-small cell lung cancer. CLDN6 expression is not required as part of the eligibiity for entry. References: 10.1016/j.annonc.2024.08.677

New BNT211 in Solid tumours, Testicular cancer, Ovarian cancer with CLDN6 Protein expression: 4

Phase 1. BNT211-01 trial. NCT04503278. N=59. Updated results showed ORR of 38% and DCR of 69%. TRAE in 88% of patients, 64% Grade 3 or more with 39% SAE. References: 10.1016/j.annonc.2024.08.678

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

Phase 3. FURLONG trial. NCT03787992. N=358. Median PFS was significantly longer in patients treated with furmonertinib versus gefitinib (20.8 vs 11.1 months) as first-line therapy in EGFR mutation-positive NSCLC. References: 35662408

New Zalontamab Brengitecan in Solid tumours with EGFR+ERBB3 EGFR:Protein expression AND ERBB3:Protein expression: 3

Phase 1. NCT05194982. N=195. BL-B01D1, showed objective response rate of 34% in patients with locally advanced or metastatic solid tumours. No relationship was found between H-scores and EGFR or HER3 and response. References: 38823410

New Zalontamab Brengitecan in Urothelial carcinoma with EGFR+ERBB3 EGFR:Protein expression AND ERBB3:Protein expression: 3

Phase 1b/2 trial. NCT05785039. N=32. Locally advanced or metastatic urothelial carcinoma. ORR was 44% (10/23), 35% confirmed. DCR was 91%, mPFS was 5.5 months at dose of 2.2 mg/kg. References: 10.1016/j.annonc.2024.08.2044

New ASP3082 in Solid tumours with KRAS G12D: 3

Phase 1. NCT05382559. N=98. ASP3082 monotherapy showed response in patients with advanced pancreatic cancer with ORR 5 of 27 (19%), colorectal cancer, and non-small cell lung cancer 3 of 13 responders. ORR was 33% at 300mg. References: 10.1016/j.annonc.2024.08.675

New RLY-2608 in Breast cancer with PIK3CA H1047R, E453K, E542K: 4

Phase 1. NCT05216432. RLY-2608. Objective responses was seen in 2 patients with advanced hormone receptor-positive breast cancer and PIK3CA mutations. References: 37916956

New STX-478 in Solid tumours with PIK3CA H1047R, H1047L, M1043, E545K, G1049R, Kinase domain mutation, Helical domain mutation: 3

Phase 1/2 trial. NCT05768139. N=61. In advanced solid tumor patients STX-478, monotherapy showed an ORR of 21% in 43 evaluable patients. DCR was 70%. References: 10.1016/j.annonc.2024.08.2266

New Puxitatug samrotecan in Solid tumours with VCTN1 Protein expression: 3

Phase 1/2a. BLUESTAR. NCT05123482. N=46. AZD8205 showed preliminary efficacy with 21% in heavily pre-treated patients with advanced and metastatic solid tumours. CtDNA reductions were seen across tumour types. References: 10.1016/j.annonc.2024.08.673

New CFT1946 in Solid tumours, Melanoma, Pancreatic adenocarcinoma with BRAF V600E, V600K, V600R: 4

Phase 1/2. NCT05668585, N=25, BRAF V600 mutant solid tumors. 1 unconfirmed partial response and 7/14 pts with stable disease or better in patients with pretreated BRAF V600 inhibitors. 8 of 11 with melanoma demonstrated tumour reduction. References: 10.1016/j.annonc.2024.08.679

New PRT3789 in Solid tumours with SMARCA4 Oncogenic mutation: 4

Phase 1. NCT05639751. Across dose levels, responses were see in PRT3789 including 3 partial responses and prolonged stable disease in patients with advanced solid tumors with SMARCA4 mutations. References: 10.1016/j.annonc.2024.08.670