Targeted treatment of non-small cell lung cancer: Focus on capmatinib with companion diagnostics

Matthew Z. Guo, Kristen A. Marrone, Alexander Spira, David M. Waterhouse, Susan C. Scott

Research output: Contribution to journalReview articlepeer-review


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® CDx, a comprehensive genomic profiling test for solid tumors, was concurrently approved as a companion diagnostic for capmatinib use. The GEOMETRY mono-1 phase II trial of capmatinib mono-therapy demonstrated an overall response rate (ORR) of 68% in treatment naïve (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 naïve and 29% in pre-treated disease was seen. This review outlines the clinical data supporting capmatinib approval in the treatment of NSCLC and FoundationOne® 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.

Original languageEnglish (US)
Pages (from-to)5321-5331
Number of pages11
JournalOncoTargets and Therapy
StatePublished - 2021


  • Capmatinib
  • FoundationOne CDx
  • MET exon 14 skipping
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)


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