Abstract：
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.
BACKGROUND: UMIN000031623.
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.
BACKGROUND: UMIN000031623.
摘要：
背景：3-4%的非小细胞肺癌（NSCLC）患者发生MET外显子14跳跃突变，<1%的患者发生MET高扩增。克唑替尼,一种选择性ATP竞争性小分子c-Met抑制剂，ALK,和ROS1酪氨酸激酶，在具有各种类型的MET激活的癌症模型中显示出活性。
方法：Co-MET研究是一项单臂2期试验，用于评估克唑替尼在MET抑制剂初治的晚期NSCLC患者中的安全性和有效性MET外显子14跳跃突变（队列1）或高MET基因拷贝数≥7（队列2）。主要终点是队列1中根据RECISTv1.1的客观缓解率（ORR）。关键的次要终点是反应持续时间(DoR)，无进展生存期（PFS），总生存期（OS），和安全。
结果：2018年3月至2020年2月，共纳入28例患者（队列1中23例，队列2中5例）。主要终点符合队列1的ORR（90%置信区间：CI）为38.1%（20.6-58.3）。中位数DoR,PFS,OS（95%CI）为7.6（1.9-NE），5.7(2.1-11.3),9.1(4.0-19.9)个月，分别,在队列1中。队列2的ORR为40.0%(18.9-92.4)。安全性信号通常与克唑替尼的已知安全性特征一致。
结论：克唑替尼在携带MET外显子14跳跃突变的非小细胞肺癌患者中的临床活性与替替尼和卡马替尼相似。
背景：UMIN000031623.
方法：Co-MET研究是一项单臂2期试验，用于评估克唑替尼在MET抑制剂初治的晚期NSCLC患者中的安全性和有效性MET外显子14跳跃突变（队列1）或高MET基因拷贝数≥7（队列2）。主要终点是队列1中根据RECISTv1.1的客观缓解率（ORR）。关键的次要终点是反应持续时间(DoR)，无进展生存期（PFS），总生存期（OS），和安全。
结果：2018年3月至2020年2月，共纳入28例患者（队列1中23例，队列2中5例）。主要终点符合队列1的ORR（90%置信区间：CI）为38.1%（20.6-58.3）。中位数DoR,PFS,OS（95%CI）为7.6（1.9-NE），5.7(2.1-11.3),9.1(4.0-19.9)个月，分别,在队列1中。队列2的ORR为40.0%(18.9-92.4)。安全性信号通常与克唑替尼的已知安全性特征一致。
结论：克唑替尼在携带MET外显子14跳跃突变的非小细胞肺癌患者中的临床活性与替替尼和卡马替尼相似。
背景：UMIN000031623.
