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Review
. 2021 Nov 23:14:5321-5331.
doi: 10.2147/OTT.S273357. eCollection 2021.

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

Matthew Z Guo  1 , Kristen A Marrone  1 , Alexander Spira  1   2   3 , David M Waterhouse  3   4 , Susan C Scott  1
Affiliations
Review

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

Matthew Z Guo et al. Onco Targets Ther. .

Abstract

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 monotherapy 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.

Keywords: FoundationOne CDx; MET exon 14 skipping; capmatinib; non-small cell lung cancer.

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Conflict of interest statement

MZG and SCS have no financial or non-financial disclosures. KAM has received consulting fees from AstraZeneca and Amgen. Honoraria: AstraZenecaConsulting fees: AstraZeneca, Amgen, Puma Biotechnology, Janssen, Mirati TherapeuticsResearch funding (institution): Bristol-Myers Squibb, AstraZeneca AS disclosures Stock and other ownership interests: Eli LillyHonoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol-Myers Squibb, BayerConsulting fees: Incyte, Amgen, Novartis, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, TakedaConsulting (institution): Array BioPharma, AstraZeneca/MedImmune, Merck, Bristol-Myers SquibbResearch funding: LAM TherapeuticsResearch funding (institution): Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, LAM Therapeutics, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius. DMW disclosures Consulting fees: Bristol-Myers Squibb, AZTherapies, AbbVie, Amgen, McGivenny Global, Janssen Oncology, Seattle Genetics, Jazz Pharmaceuticals, Exelixis, Eisai, EMD Serono, Merck, Pfizer, Mirati Therapeutics, Regeneron/SanofiSpeakers’ bureau: Bristol-Myers Squibb, Janssen Oncology, Merck, AstraZeneca, Amgen, EMD Serono.

Figures

Figure 1
Figure 1
Capmatinib selectively targets MET on NSCLC tumor cells, inhibiting both wildtype and METex14 which lacks ubiquitination sites required for receptor degradation.
See this image and copyright information in PMC

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