Abstract Background: 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). 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, 7 lung, 4 other tumor types). Four patients had a partial response (PR), 10 had stable disease (SD), 13 had progressive disease (PD); one unevaluable. ORR was 14% (4/28, 90%; CI 5.0-29.8%). Median (m) PFS was 3.4 months (90% CI 1.8–3.7), mOS 7.1 months (90% CI 5.0–11.5). C2 included 14 of 20 patients (5 gastrointestinal, 6 lung, 3 other). Two patients had PR, 4 SD (2 6 months), and 4 PD were observed. ORR was 14% (2/14, 90% CI 2.6–38.5%). mPFS and mOS were 2.0 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–NA) versus 1.7 months (90% CI 1.1–3.7). Conclusion: Crizotinib demonstrated clinical activity across tumors with METamp and METex14.Subprotocol C1, but not C2, met its primary endpoint. In METex14 disease, a read count cutoff 50,000 may help distinguish true pathogenic variants from low-level splice transcripts and enable more accurate classification.
Coleman et al. (Tue,) studied this question.