A profile on capmatinib in treating adult patients with metastatic NSCLC tumors with MET exon 14 skipping mutations

ABSTRACT

Introduction

: Clinical studies of MET-targeted treatments have so far failed to provide adequate outcomes. Capmatinib, a newly designed MET receptor inhibitor, has demonstrated considerable anticancer efficacy in patients with advanced NSCLC who have a MET exon 14 skipping mutation.

Areas covered

: This review offers a summary of the findings from capmatinib clinical studies in NSCLC patients with a MET exon 14 skipping mutation, as well as preclinical data and post-market reporting of capmatinib.

Expert opinion

: Capmatinib has a tolerable safety profile and preliminary evidence of effectiveness in patients with a MET exon 14 skipping mutation, according to data from a phase 1 clinical study. The GEOMETRY mono-1 phase 2 study revealed objective response rates of 68% and 41%, and median OS of 20.8 and 13.6 months in treatment-naive and pretreated MET exon 14 skipping mutant patients, respectively. Furthermore, capmatinib penetrates the blood–brain barrier, and capmatinib activity in the brain was shown to be encouraging in the study. However, the effectiveness of immunotherapy for MET exon 14 skipping mutation remains debatable. To enhance therapy choices, researchers have begun to focus on the mechanisms of intrinsic and acquired resistance of the MET exon 14 skipping mutation.

KEYWORDS:

• Capmatinib
• drug resistance
• immunotherapy
• MET exon 14 skipping
• MET inhibitor
• NSCLC
• targeted therapy

Article highlights

• Capmatinib has received regulatory approval for METex14 NSCLC in several countries.

• Capmatinib is highly effective in treating METex14 NSCLC, with particularly good outcomes as the first-line treatment (ORR 68%, median OS 20.8 months).

• Capmatinib crosses the blood–brain barrier, and its activity in the brain is promising.

• The majority of adverse events of capmatinib were of grade 1 or 2, predictable, and reversible with dose adjustments.

• The efficacy of immunotherapy for METex14 NSCLC remains controversial.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.