Crizotinib in Patients with Tumors with MET Amplification or Exon 14 Deletion: Results from the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocols C1 and C2

作者：Niamh Coleman, Zihan Wei, Anthony John Iafrate, James A. Zwiebel, Elad Sharon, Robert J. Gray, Victoria Wang, Lisa M. McShane, Larry Rubinstein, David R. Patton, Paul Mickey Williams, Stanley R. Hamilton, Naoko Takebe, Travis Williams, Jessica Jones Croley, Adedayo A. Onitilo, James V. Tricoli, Ju Cheng, Chris Karlovich, Barbara A. Conley, Carlos L. Arteaga, Lyndsay Harris, Peter James O'Dwyer, David S. Hong, Alice P. Chen, Keith T. Flaherty · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1078-0432.ccr-25-1247 · 被引用次数：1 · 研究领域：Lung Cancer Treatments and Mutations、Fibroblast Growth Factor Research、Liver physiology and pathology

PURPOSE: The NCI-MATCH trial enrolled patients to subprotocols C1 and C2 to evaluate the METtyrosine kinase inhibitor crizotinib for efficacy in patients with MET amplification (METamp; C1) or MET exon 14 skipping mutation (METex14; C2). PATIENTS AND METHODS: Tumors harboring METamp or METex14 were confirmed by Oncomine assay, RNA sequencing, and anchored multiplex PCR. Patients received 250 mg crizotinib orally daily until disease progression or unacceptable toxicity. Primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), 6-month PFS, and overall survival (OS). RESULTS: C1 efficacy analysis comprised 28 of 44 enrolled patients (17 gastrointestinal, seven lung, and four other tumor types). Four patients had a partial response (PR), 10 had stable disease (SD), and 13 had progressive disease (PD); one was unevaluable. The ORR was 14% [four of 28; 90% confidence interval (CI), 5%-29.8%]. The median PFS (mPFS) was 3.4 months (90% CI, 1.8-3.7), and the median OS (mOS) was 7.1 months (90% CI, 5-11.5). C2 included 14 of 20 patients (five gastrointestinal, six lung, and three other). Two patients had PR, four SD (2 > 6 months), and four PD were observed. The ORR was 14% (two of 14; 90% CI, 2.6%-38.5%). mPFS and mOS were 2 months (90% CI, 1.4-4.1) and 10.2 months (90% CI, 2.3-19.6). METex14 cases with read count ≥50,000 had mPFS 8.8 months [90% CI, 2.1-NR(not reached)] versus 1.7 months (90% CI, 1.1-3.7). CONCLUSIONS: Crizotin...