Capmatinib plus nivolumab in pretreated patients with EGFR wild-type advanced non-small cell lung cancer.

Dysregulated MET is an established oncogenic driver in non-small cell lung cancer (NSCLC). MET signaling may also suppress anticancer immune responses. Concomitant MET inhibition with capmatinib (a MET inhibitor) synergistically enhanced the efficacy of immunotherapies in murine cancer models, regardless of tumor dependency to MET signaling. Here, we report results of a multicenter, open-label, phase 2 study of capmatinib plus nivolumab (a PD-1 inhibitor) in patients with EGFR wild-type advanced NSCLC, previously treated with platinum-based chemotherapy. Patients were allocated into high-MET or low-MET groups according to MET expression determined by immunohistochemistry, MET gene copy number as assessed by fluorescence in-situ hybridization, and presence of MET exon 14 skipping mutation, then received capmatinib 400 mg, oral, twice daily in combination with nivolumab 3 mg/kg intravenously every 2 weeks. The primary endpoint was investigator-assessed 6-month progression-free survival (PFS) rate per RECIST v1.1. The primary endpoint was met in both the high-MET (N = 16) and low-MET (N = 30) groups. In the high-MET and low-MET groups, respectively, the estimated mean 6-month PFS rate (95 % credible interval) by Bayesian analysis was 68.9 % (48.5-85.7) and 50.9 % (35.6-66.4). The Kaplan-Meier median PFS (95 % CI) was 6.2 months (3.5-19.2) and 4.2 months (1.8-7.4). The overall response rate (95 % CI) was 25.0 % (7.3-52.4) and 16.7 % (5.6-34.7). Most frequent treatment-related adverse events (≥30 % any grade, N = 46) were nausea (52.2 %), peripheral edema (34.8 %), and increased blood creatinine (30.4 %). Capmatinib plus nivolumab showed clinical activity and manageable safety in pretreated patients with advanced EGFR wild-type NSCLC, independent of MET status. ClinicalTrials.gov NCT02323126.

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Copyright © 2024. Published by Elsevier B.V.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Enriqueta Felip: Consulting or advisory role for Abbvie, Amgen, Astra Zeneca, Bayer, Beigene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann – La Roche, Genentech, Gilead, Glaxo Smith Kline, Janssen, Medscape, Merck Serono, Merck Sharp & Dohme, Novartis, Peervoice, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Touch Oncology, Turning Point Therapeutics. Giulio Metro: No conflict of interest to declare. Daniel S. W. Tan: Consulting or advisory role for Novartis, Merck, Loxo, AstraZeneca, Roche, Pfizer, Amgen, and Janssen; travel, accommodation, and expenses from Pfizer, Boehringer Ingelheim, and Roche; honoraria from Bristol-Myers Squibb, Takeda, Novartis, Roche, and Pfizer; and research funding (institution) from Novartis, GlaxoSmithKline, Amgen, and AstraZeneca. Juergen Wolf: Advisory boards and lecture fees for Amgen, AstraZeneca, Bayer, Blueprint, BMS, Boehringer-Ingelheim, Chugai, Daiichi Sankyo, Ignyta, Janssen, Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; research support (to institution) from BMS, Janssen Pharmaceutica, Novartis, Pfizer. Michael Mark: Consulting fees from Amgen, Astra Zeneca, BMS, MSD, Pfizer, Takeda, Roche; travel support from Astra Zeneca, Roche, Takeda. Michael Boyer: Advisory board for Merck Sharpe and Dohme, Astra Zeneca, Amgen, Bristol Myers Squibb, and Roche. Brett G. M. Hughes: Advisory board for Novartis, Merck Sharpe and Dohme, AstraZeneca, Roche, Pfizer, Amgen, Bristol-Myers Squibb, Takeda, Sanofi and Eisai; and research funding (institution) from Amgen. Alessandra Bearz: Consulting/advisory fees from Pfizer, MSD, AstraZeneca, Eli Lilly, Boehringer, Ingelheim, Sanofi. Denis Moro-Sibilot: Consulting/advisory fees from Eli Lilly, AstraZeneca, BMS, Novartis, MSD, Daiichi Sankyo, Janssen, Pfizer, Roche, Abbvie, Takeda, Amgen; research funding to Institution from Eli Lilly, MSD, Astra Zeneca, Pfizer, BMS, Roche; travel Support from Roche, Takeda, MSD. Xiuning Le: Consulting/advisory fees from Eli Lilly, EMD Serono (Merck KGaA), AstraZeneca, Spectrum Pharmaceutics, Novartis, Regeneron, Boehringer Ingelheim, Hengrui Therapeutics, Bayer, Teligene, Taiho, Daiichi Sankyo, Janssen, Blueprint Medicines, Sensei Biotherapeutics, SystImmune, ArriVent, Abion, and Abbvie; research funding to Institution from Eli Lilly, EMD Serono, ArriVent, Dizal, Teligene, Regeneron, Janssen, ThermoFisher, Takeda, and Boehringer Ingelheim; travel support from EMD Serono, Janssen, and Spectrum Pharmaceutics; stock options from BlossomHill. Javier Puente: Research funding from Astellas Pharma, Pfizer; consulting or advisory role from Pfizer, Astellas Pharma, Janssen-Cilag, Merck Sharp & Dohme, Bayer, Roche, Bristol Myers Squibb, Clovis Oncology, Ipsen, Eisai, Sanofi; honoraria from Pfizer, Bristol Myers Squibb, Ipsen, AstraZeneca, Roche, MSD Oncology, Janssen-Cilag, Astellas Pharma, EUSA Pharma, Eisai, Pierre Fabre, Sanofi, Bayer; travel/accommodations/expenses from Pfizer, Roche, Janssen-Cilag, Bristol Myers Squibb, MSD Oncology. Bartomeu Massuti: Consulting fees from AstraZeneca, Roche and Sanofi; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, MSD, Roche and Takeda; and support for attending meetings and/or travel from AstraZeneca and MSD. Ralph Tiedt: Past employee of Novartis at the time of the study; current employee of Monte Rosa Therapeutics. Yingying Wang: Employee of Novartis. Chao Xu: Employee of Novartis. Feby I. Mardjuadi: Employee of Novartis. Manuel Cobo: Speaker for Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Kyowa, Pierre-fabre, Novocure, Sanofi, Jansen; consultant or advisory role for Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Lilly, MSD, Takeda, Phyzer, Kyowa, Sanofi, Jansen.