Multicenter study of crizotinib for tumors with MET amplification or exon 14 deletion: NCI-MATCH ECOG-ACRIN trial subprotocols C1 and C2

The multicenter NCI-MATCH trial evaluated the MET TKI crizotinib for tumors with MET amplification (subprotocol C1; n=44) or MET exon 14 skipping mutation (subprotocol C2; n=20). Patients received oral crizotinib 250 mg once daily until disease progression or unacceptable toxicity. Primary endpoint was objective response rate. C1 efficacy analysis comprised 28 of 44 patients (17 gastrointestinal, 7 lung, 4 other tumor types). Four patients had a partial response (ORR 14%; 90% CI 5.0-29.8), while 10 had stable disease. Median progression-free survival was 3.4 months (90% CI 1.8-3.7) and median overall survival was 7.1 months (5.0-11.5). C2 efficacy analysis included 14 of 20 patients (5 gastrointestinal, 6 lung, 3 other). Two patients had a partial response (ORR 14%; 90% CI 2.6-38.5), while 4 patients had stable disease. Median PFS and median OS were 2.0 months (90% CI 1.4-4.1) and 10.2 months (2.3-19.6). The authors conclude that crizotinib demonstrated clinical activity for tumors with MET amplification or exon 14 skipping mutation. Subprotocol C1, but not C2 met its primary endpoint.