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Phase 2 trial of crizotinib in Japanese patients with advanced NSCLC harboring a MET gene alteration: a Co-MET study
Kaname Nosaki1, Kiyotaka Yoh2, Ryo Toyozawa3
1Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Background:
MET exon 14 skipping mutations occur in 3-4% and MET high amplifications occur in < 1% of patients with non-small-cell lung cancer (NSCLC). Crizotinib, a selective ATP-competitive small-molecule inhibitor of c-Met, ALK, and ROS1 tyrosine kinases, has shown activity in cancer models with various types of MET activation.
Methods:
The Co-MET study is a single-arm phase 2 trial to assess the safety and efficacy of crizotinib in MET inhibitor-naïve patients with advanced NSCLC harboring MET exon 14 skipping mutation (cohort 1) or high MET gene copy number of ≥ 7 (cohort 2). The primary endpoint was the objective response rate (ORR) per RECIST v1.1 by independent radiology review in cohort 1. The key secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety.
Results:
A total of 28 patients (23 in cohort 1 and 5 in cohort 2) were enrolled between March 2018 and February 2020. The primary endpoint was met as the ORR (90% confidence interval: CI) in cohort 1 was 38.1% (20.6-58.3). Median DoR, PFS, and OS (95% CI) were 7.6 (1.9-NE), 5.7 (2.1-11.3), 9.1 (4.0-19.9) months, respectively, in cohort 1. ORR in cohort 2 was 40.0% (18.9-92.4). The safety signals were generally consistent with the known safety profile of crizotinib.
Conclusions:
Crizotinib showed a clinical activity similar to that of tepotinib and capmatinib in patients with NSCLC harboring MET exon 14 skipping mutations.
Clinical Trial Information:
UMIN000031623.
Insights
Crizotinib demonstrated significant clinical activity in non-small-cell lung cancer (NSCLC) patients with MET exon 14 skipping mutations. The study met its primary endpoint, showing promising objective response rates and survival outcomes.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- MET exon 14 skipping mutations and MET high amplifications are key drivers in a subset of non-small-cell lung cancer (NSCLC) patients.
- Crizotinib is an established inhibitor targeting MET, ALK, and ROS1 tyrosine kinases, showing potential in MET-altered cancers.
Purpose of the Study:
- To evaluate the safety and efficacy of crizotinib in MET inhibitor-naïve advanced NSCLC patients.
- To assess crizotinib's activity in patients with MET exon 14 skipping mutations (cohort 1) and high MET gene copy number (cohort 2).
Main Methods:
- A single-arm, phase 2 trial (Co-MET study) enrolled 28 NSCLC patients.
- Primary endpoint: Objective Response Rate (ORR) in cohort 1 (MET exon 14 skipping mutations).
- Secondary endpoints included Duration of Response (DoR), Progression-Free Survival (PFS), Overall Survival (OS), and safety.
Main Results:
- The study met its primary endpoint with an ORR of 38.1% in cohort 1.
- Median DoR, PFS, and OS in cohort 1 were 7.6, 5.7, and 9.1 months, respectively.
- Cohort 2 showed an ORR of 40.0%, with safety profiles consistent with known crizotinib data.
Conclusions:
- Crizotinib exhibits significant clinical activity in NSCLC patients with MET exon 14 skipping mutations.
- The efficacy of crizotinib is comparable to other MET inhibitors like tepotinib and capmatinib in this patient population.
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