Capmatinib response in patients with advanced non–small cell lung cancer (NSCLC) harboring focal MET amplifications: Analysis from the phase 2, multicohort GEOMETRY mono-1 study

Background: MET amplifications (METamp) occur in 1–6% of patients (pts) with NSCLC and are associated a poor prognosis. Capmatinib is highly selective potent inhibitor (METi) antitumor activity pretreated treatment-naive pts MET-amplified (gene copy number [GCN] 310) NSCLC. Focal METamp relatively high GCN may be predictor benefit from METi. In this retrospective analysis GEOMETRY mono-1 (NCT02414139), we aimed to determine the response capmatinib according focality detected cell-free DNA (cfDNA) using blood-based assay. Materials Methods: Pretreated (1 or 2 prior lines) EGFR wild-type, ALK-negative, exon 14 skipping–negative, stage IIIB/IV were grouped into cohorts C1a, C1b, C2, C3 based on different levels amp by FISH tumor tissue. Pts received 400 mg twice daily. cfDNA isolated blood plasma samples collected at baseline was enriched RNA-bait–based hybrid capture analyzed next-generation sequencing (PanCancer assay 1.0, NGDx, Novartis). defined PureCN pipeline that estimates gene-level log-ratio relative normal samples, adjusting for gene probe signal variation. called focally amplified if P value <0.001 reached 90th percentile all genes. The overall rate (ORR) Blinded Independent Review Committee descriptively compared between focal vs nonfocal (data cutoff, August 2021). Results: 195 across 4 had FISH. Of these, 113 successfully (C1a [n = 29], C1b 32], C2 31], 21]). Baseline characteristics comparable who (n 113) not 82) 18) 95) METamp. METamp, most C1a (14 18 [78%]). distribution similar but more responders found (ORR, 57% 13%). 3 32 (9%) METamp; (Table).Tabled 1CohortMET FISHParameterFocal METampNonfocal METampPts analyzedAll cohortC1a≥10N14152969ORR, n (%)8 (57)2 (13)10 (34)20 (29)C1b≥6 <10N3293242ORR, (%)2 (67)1 (3)3 (9)5 (12)C2≥4 <6N0313154ORR, (%)-2 (6)2 (6)5 (9)C3<4N1202130ORR, (%)0 (0)1 (5)1 (5)2 (7) Open table new tab Conclusions: status, including determined blood. For MET- FISH, numerically higher proportion observed Given small sample size, larger study needed verify result. Conflict interest: Ownership: Juergen Wolf: None Markus Riester, Lexiang Ji, Anna Robeva, Aislyn Boran: Novartis stock Advisory Board: Consulting advisory role Abbvie, AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Chugai Pharma, Ignyta, Lilly, MSD Oncology, Novartis, Pfizer, Roche, Janssen, Loxo/Lilly, Blueprint Medicines, Amgen, Takeda, Bayer, Daiichi Sankyo Europe GmbH, Seattle Genetics Edward B. Garon: Consultant and/or advisor ABL-Bio, Boehringer-Ingelheim, Bristol Myers Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Gilead, GlaxoSmithKline, Merck, Natera, Personalis, Regeneron, Sanofi, Shionogi, Xilio. Daniel S. W. Tan: Consulting/advisory DKSH, C4 Therapeutics, GSK Board Directors: Corporate-sponsored Research: Research funding Janssen Grant/research support Dynavax Technologies, Genentech, Iovance Biotherapeutics, Mirati Neon, (payments institution) ACM Biolabs, Amgen Rebecca Heist: To institution (not self) Agios, Turning Point, Daichii Sankyo, Mirati, Corvus, Exelixis, Erasca Other Substantive Relationships: Honoraria MSD, Pharma Europe, Loxo, Genetics, Takeda Sylvie Le Mouhaer, Lauren Fairchild, Employment Serono