Capmatinib in <i>MET</i> Exon 14–Mutated or <i>MET</i> -Amplified Non–Small-Cell Lung Cancer
Jürgen Wolf, Takashi Seto, Ji‐Youn Han, Noemı́ Reguart, Edward B. Garon, Harry J.M. Groen, Daniel S.W. Tan, Toyoaki Hida, Maja J.A. de Jonge, Sergey Orlov, Egbert F. Smit, Pierre-Jean Souquet, Johan Vansteenkiste, Maximilian J. Hochmair, Enriqueta Felip, Makoto Nishio, Michael Thomas, Kadoaki Ohashi, Ryo Toyozawa, Tobias R. Overbeck, Filippo de Marinis, Tae Min Kim, Eckart Laack, Anna Robeva, Sylvie Le Mouhaër, Maeve Waldron-Lynch, B. Sankaran, O. Alejandro Balbin, Xiaoming Cui, Monica Giovannini, Mikhail Akimov, Rebecca S. Heist
Abstract
BACKGROUND: amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS: amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS: amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS: -amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).