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

Matthew Z Guo1, Kristen A Marrone1, Alexander Spira1,2,3

  • 1Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.

Oncotargets and Therapy
|December 2, 2021
PubMed

Insights

Capmatinib is a targeted therapy for non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations. Clinical data supports its approval and use with FoundationOne CDx companion diagnostic.

Area of Science:

  • Oncology
  • Genomics
  • Pharmacology

Background:

  • MET dysregulation, via MET exon 14 skipping (METex14) or gene amplification, drives tumorigenesis in non-small cell lung cancer (NSCLC).
  • MET dysregulation is linked to poorer outcomes with chemotherapy in NSCLC.
  • Capmatinib, approved in 2020, is the first FDA-approved targeted therapy for NSCLC harboring METex14 skipping mutations.

Purpose of the Study:

  • To review clinical data supporting capmatinib approval for NSCLC treatment.
  • To discuss the approval of FoundationOne CDx as a companion diagnostic for capmatinib.
  • To outline capmatinib's clinical administration, compare it with other MET-targeted therapies, and discuss ongoing research.

Main Methods:

  • Review of clinical data from the GEOMETRY mono-1 phase II trial.
  • Analysis of response rates in treatment-naïve and pre-treated NSCLC patients with METex14 skipping or MET amplification.
  • Evaluation of capmatinib's dosing, toxicity, and comparative efficacy.

Main Results:

  • Capmatinib demonstrated an overall response rate (ORR) of 68% in treatment-naïve and 41% in pre-treated METex14 skipping advanced NSCLC.
  • In MET-amplified NSCLC, ORRs were 40% (treatment-naïve) and 29% (pre-treated).
  • FoundationOne CDx was concurrently approved as a companion diagnostic.

Conclusions:

  • Capmatinib is an effective targeted therapy for NSCLC with METex14 skipping mutations.
  • FoundationOne CDx is crucial for identifying patients eligible for capmatinib treatment.
  • Further research is ongoing to explore capmatinib in combination therapies for NSCLC.
Keywords:
FoundationOne CDxMET exon 14 skippingcapmatinibnon-small cell lung cancer

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