Phase 2 trial of crizotinib in Japanese patients with advanced NSCLC harboring a MET gene alteration: a Co-MET study.

Autor: Nosaki K; Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan., Yoh K; Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. kyoh@east.ncc.go.jp., Toyozawa R; Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan., Horinouchi H; Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan., Morise M; Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan., Ohashi K; Department of Respiratory Medicine, Okayama University Hospital, Okayama, Japan., Murakami H; Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan., Satouchi M; Department of Thoracic Oncology, Hyogo Cancer Center, Akashi, Japan., Sakakibara-Konishi J; Department of Respiratory Medicine, Faculty of Medicine, Hokkaido University, Sapporo, Japan., Yano S; Department of Respiratory Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Ishikawa, Japan., Okumura F; Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan., Matsumoto S; Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan., Shimokawa M; Department of Biostatistics, Yamaguchi University Graduate School of Medicine, Ube, Japan., Seto T; Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan., Goto K; Department of Thoracic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Jazyk: angličtina
Zdroj: International journal of clinical oncology [Int J Clin Oncol] 2024 Aug; Vol. 29 (8), pp. 1142-1151. Date of Electronic Publication: 2024 May 17.
DOI: 10.1007/s10147-024-02543-x
Abstrakt: 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.
(© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)
Databáze: MEDLINE
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