Targeted Treatment of Non-Small Cell Lung Cancer: Focus on Capmatinib with Companion Diagnostics

MET dysregulation promoting tumorigenesis in non-small cell lung cancer (NSCLC) is associated with worse outcomes following chemotherapy as compared to non-driver mutated NSCLC and occurs either through mutations causing MET exon 14 skipping (METex14) or gene amplification and overexpression that result in enhanced receptor signaling. Capmatinib is the first FDA-approved targeted therapy for NSCLC with METex14 skipping mutations, approved in 2020. FoundationOne (R) CDx, a comprehensive genomic profiling test for solid tumors, was concurrently approved as a companion diag-nostic for capmatinib use. The GEOMETRY mono-1 phase II trial of capmatinib mono -therapy demonstrated an overall response rate (ORR) of 68% in treatment naive (n=28) and 41% in pre-treated (n=69) METex14 skipping advanced NSCLC; in MET amplified advanced NSCLC (gene copy number >= 10) ORRs of 40% in treatment naive and 29% in pre-treated disease was seen. This review outlines the clinical data supporting capmatinib approval in the treatment of NSCLC and FoundationOne (R) CDx approval as a companion diagnostic. We detail the practical clinical administration of capmatinib, including dosing and toxicity management, compare capmatinib to other approved and investigational MET-targeted therapies, discuss limitations of capmatinib, and highlight ongoing trials of capmatinib in combinatorial approaches.

Automated summary

Capmatinib is the first FDA-approved targeted therapy for NSCLC with METex14 skipping mutations, approved in 2020. Studies have shown significant efficacy of capmatinib in both treatment naive and pre-treated METex14 skipping NSCLC patients, while FoundationOne(R) CDx was approved as a companion diagnostic.