Savolitinib in MET-amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.

MET proto-oncogene amplification (METamp) is associated with poor prognosis in gastric or gastroesophageal junction (G/GEJ) cancer. Currently, effective targeted therapies for G/GEJ cancer harboring METamp remain unavailable, and clinical evidence supporting the use of MET inhibitors in this disease population is limited. Here we report the results of a phase 2 study of savolitinib, an oral MET inhibitor, in patients with METamp G/GEJ cancer. This open-label, multicenter, phase 2 trial in China comprised an exploratory phase and a pivotal phase. Patients with METamp (gene copy number ≥10 for pivotal phase), locally advanced or metastatic G/GEJ cancer that had progressed following ≥1 (≥2 for pivotal phase) prior lines of systemic therapy received savolitinib orally. The primary endpoint was objective response rate (ORR) by independent review committee in the pivotal phase. In total, 110 patients were enrolled and received savolitinib, including 45 in the exploratory phase and 65 in the pivotal phase. Independent review committee-assessed ORR was 32.3% (95% confidence interval 21.2-45.1%) in the pivotal phase, which met the predefined efficacy threshold (lower limit of 95% confidence interval of ORR ≥15%). Among all patients enrolled (n = 110), grade ≥3 treatment-related adverse events were reported in 38 patients (34.5%); one (0.9%) treatment-related death occurred. Savolitinib monotherapy showed encouraging antitumor activities and a tolerable safety profile in heavily treated, later-line METamp G/GEJ cancers, supporting further investigation in randomized controlled trials. ClinicalTrials.gov identifier: NCT04923932 .