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

Abstract

Matthew Z Guo,1 Kristen A Marrone,1 Alexander Spira,1– 3 David M Waterhouse,3,4 Susan C Scott1 1Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA; 2Virginia Cancer Specialists Research Institute, Fairfax, VA, USA; 3US Oncology, The Woodlands, TX, USA; 4Oncology Hematology Care, Cincinnati, OH, UsaCorrespondence: Susan C ScottJohns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, 201 N Broadway, Baltimore, MD, 21287, USATel [phone]Fax [phone]Email [email protected]: 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: capmatinib, MET exon 14 skipping, non-small cell lung cancer, FoundationOne CDx

Keywords

• capmatinib
• met exon 14 skipping
• non-small cell lung cancer
• foundationone cdx