Dysregulation of receptor tyrosine kinase MET by various mechanisms occurs in 3-4% of NSCLC and is associated with unfavorable prognosis. While MET is a validated drug target in lung cancer the best biomarker strategy for enrichment of susceptible patient population still remains to be defined. Towards this end we analyze here primary data from phase I dose expansion study of MET inhibitor capmatinib in patients with advanced MET-dysregulated NSCLC.
Eligible patients (≥18 years; ECOG PS ≤2) with MET-dysregulated advanced NSCLC, defined as either, (1) MET IHC 2+ or 3+ or H-score ≥150, or MET/centromere ratio ≥2.0 or GCN ≥5, or (2) EGFRwt and centrally assessed MET IHC 3+, received capmatinib at recommended dose of 400 mg (tablets) or 600 mg (capsules) BID. Primary objective was to determine safety and tolerability; key secondary objective was to explore antitumor activity. Exploratory endpoint was correlation of clinical activity with different biomarker formats.
Of 55 patients with advanced MET-dysregulated NSCLC, 40/55 (73%) had received ≥2 prior systemic therapies. All patients discontinued treatment, primarily due to disease progression (69.1%). Median treatment duration was 10.4 weeks. Overall response rate (ORR) per RECIST was 20% (95% CI, 10.4-33.0). In patients with MET gene copy number (GCN) ≥6 (n=15), ORR by both investigator and central assessments was 47%. Median progression-free survival per investigator for patients with MET GCN ≥6 was 9.3 months (95% CI, 3.8-11.9). Tumor responses were observed in all four patients with METex14. Most common toxicities were nausea (42%), peripheral edema (33%), and vomiting (31%).
MET GCN ≥6 and/or METex14 are suited to predict clinical activity of capmatinib in patients with NSCLC (NCT01324479).
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Related Posts
Advertisement
Meeting Coverage
- ASCO – Lung CancerASCO.20 Virtual Scientific Program, held May 29 - 31, brought professionals from all over the world together to hear the brightest minds in oncology present state-of-the-art treatment modalities and new therapies.
- AACR-2020The American Association for Cancer Research is the world's oldest and largest professional association related to cancer research.
- ACC 2020The American College of Cardiology decided to cancel ACC.20/WCC due to COVID-19, which was scheduled to take place March 28-30 in Chicago. However, ACC.20/WCC Virtual Meeting continues to release cutting edge science and practice changing updates for cardiovascular professionals on demand and free through June 2020.