Purpose: MET gene amplification is associated with poor prognosis in gastric/gastroesophageal junction/esophageal (G/GEJ/E) cancers. We determined antitumor activity, safety, and pharmacokinetics of the small-molecule MET inhibitor AMG 337 in MET-amplified G/GEJ/E adenocarcinoma or other solid tumors. Experimental Design: In this phase 2, single-arm study, adults with MET-amplified G/GEJ/E adenocarcinoma (Cohort 1) or other MET-amplified solid tumors (Cohort 2) received AMG 337 300 mg/d orally in 28-day cycles. The primary endpoint was objective response rate (ORR; Cohort 1). Secondary endpoints included ORR (Cohort 2), progression-free survival (PFS), overall survival (OS), and safety. Results: Of 2101 patients screened for MET amplification, 132 were MET-amplified and 60 were enrolled: 45 in Cohort 1, and 15 in Cohort 2. Fifty-six patients (97%) had metastatic disease; 57 had prior lines of therapy (1 prior line, 29%; ≥ 2 prior lines, 69%). A protocol-permitted review showed efficacy that was lower-than-expected based on preliminary data from a first-in-human study, and enrollment was stopped. Fifty-eight patients received ≥1 AMG 337 dose. ORR in Cohort 1 was 18% (8 partial responses). No responses were observed in Cohort 2. Of 54 evaluable patients, median (95% CI) PFS and OS were 3.4 (2.2-5.0) and 7.9 (4.8-10.9) months, respectively. The most frequent adverse events (AEs) were headache (60%), nausea (38%), vomiting (38%), and abdominal pain, decreased appetite, and peripheral edema (33% each); 71% had grade ≥3 AEs and 59% had serious AEs. Conclusions: AMG 337 showed antitumor activity in MET-amplified G/GEJ/E adenocarcinoma but not in MET-amplified non-small-cell lung cancer.
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