Introduction: Activation of the MET pathway through MET amplifications or mutations is present in 3-4% of stage IV non-squamous non-small cell lung cancers (NSCLC). High MET amplifications and exon 14 skipping mutations are associated with poor prognosis: new treatments are needed for these patients. Capmatinib is a highly selective, potent small-molecule MET inhibitor with antitumor activity in NSCLC in vitro and in vivo. Areas covered: This article provides an overview of the capmatinib clinical development program in NSCLC, both as monotherapy in NSCLC with a dysregulated MET pathway, and in combination with epidermal growth factor receptor (EGFR) inhibitor therapy in EGFR-mutant NSCLC with MET-based acquired resistance to previous EGFR inhibition. Expert opinion: In the GEOMETRY Mono-1 study, treatment with capmatinib resulted in high response rates in stage IV NSCLC with MET exon 14 skipping mutations, particularly in first line, supporting testing for this biomarker at the time of diagnosis. Durable responses have been reported and results in MET-amplified NSCLC are eagerly anticipated. In EGFR-mutant NSCLC, notable responses have been observed in combination with an EGFR-tyrosine kinase inhibitor (TKI) in case of acquired resistance to EGFR-TKIs based on high MET amplification.
Keywords: Capmatinib; MET inhibitor; NSCLC; non-small cell lung cancer; tyrosine kinase inhibitor.