Molecular profiling of non-small cell lung cancer (NSCLC) in the past decade has revealed numerous oncogenic driver events in NSCLC leading to several highly effective therapies. While a promising target, small-molecule inhibition of MET signaling has proven difficult. Capmatinib is a specific inhibitor of MET with Food and Drug Administration (FDA) accelerated approval in 2020 for the treatment of NSCLC harboring MET exon 14 skipping mutations. As a first-line therapy, 68% of patients in phase II clinical trials responded to capmatinib with a median duration of 12.6 months and a manageable safety profile. Although FDA approval is currently limited to MET exon 14 skipping mutations, capmatinib has shown potential in other subsets of MET-dysregulated NSCLC for which ongoing studies are underway. This review covers the preclinical and early clinical data leading to capmatinib's approval, discusses the management of treatment-related toxicities, and offers potential avenues of further research.
Keywords: Capmatinib; Hepatocyte growth factor (HGF; MET) inhibitors; INC-280; INC-28060; Non-small cell lung cancer (NSCLC) therapy; Oncolytic drugs; Tabrecta.
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