The Development and Role of Capmatinib in the Treatment of MET-Dysregulated Non-Small Cell Lung Cancer-A Narrative Review

• Published in: Cancers Vol. 15; no. 14; p. 3561
• Main Authors: Hsu, Robert, Benjamin, David J, Nagasaka, Misako
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.07.2023; MDPI
• Subjects: Antimitotic agents; Antineoplastic agents; Antitumor activity; Biological products; c-Met protein; Clinical trials; Competition; Development and progression; Drug approval; Drug dosages; Enzyme inhibitors; Epidermal growth factor; Epidermal growth factor receptors; FDA approval; Gene amplification; Immunotherapy; Kinases; Ligands; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Medical prognosis; Mutation; Non-small cell lung carcinoma; Pharmacokinetics; Protein-tyrosine kinase; Proteins; Respiratory agents; Review; Small cell lung carcinoma; Solid tumors; Tyrosine; detection; tyrosine kinase inhibitor; NSCLC; MET dysregulation; capmatinib
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers15143561

Non-small cell lung cancer (NSCLC) is a leading cause of death, but over the past decade, there has been tremendous progress in the field with new targeted therapies. The mesenchymal-epithelial transition factor ( ) proto-oncogene has been implicated in multiple solid tumors, including NSCLC, and dysregulation in NSCLC from can present most notably as exon 14 skipping mutation and amplification. From this, tyrosine kinase inhibitors (TKIs) have been developed to treat this dysregulation despite challenges with efficacy and reliable biomarkers. Capmatinib is a Type Ib TKI first discovered in 2011 and was FDA approved in August 2022 for advanced NSCLC with exon 14 skipping mutation. In this narrative review, we discuss preclinical and early-phase studies that led to the GEOMETRY mono-1 study, which showed beneficial efficacy in exon 14 skipping mutations, leading to FDA approval of capmatinib along with Foundation One CDx assay as its companion diagnostic assay. Current and future directions of capmatinib are focused on improving the efficacy, overcoming the resistance of capmatinib, and finding approaches for new indications of capmatinib such as acquired amplification from epidermal growth factor receptor ( ) TKI resistance. Clinical trials now involve combination therapy with capmatinib, including amivantamab, trametinib, and immunotherapy. Furthermore, new drug agents, particularly antibody-drug conjugates, are being developed to help treat patients with acquired resistance from capmatinib and other TKIs.