A Multicenter Phase II Study of AMG 337 in Patients with -Amplified Gastric/Gastroesophageal Junction/Esophageal Adenocarcinoma and Other -Amplified Solid Tumors.

Purpose: 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 -amplified G/GEJ/E adenocarcinoma or other solid tumors. In this phase II, single-arm study, adults with -amplified G/GEJ/E adenocarcinoma (cohort 1) or other -amplified solid tumors (cohort 2) received AMG 337 300 mg/day 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 amplification, 132 were -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 -amplified G/GEJ/E adenocarcinoma but not in -amplified non-small-cell lung cancer..