Savolitinib In Met-Amplified Gastric Or GEJ Adenocarcinoma

Key Takeaways

• Responses were observed in roughly one-third of the pivotal cohort, and the predefined efficacy threshold was met.
• The pivotal phase enrolled later-line patients with MET gene copy number of at least 10 after at least two prior systemic lines.
• Grade 3 or higher treatment-related adverse events were reported in about one-third overall, and one treatment-related death occurred.

Savolitinib produced a 32.3% objective response rate in the pivotal cohort of MET-amplified advanced gastric or gastroesophageal junction adenocarcinoma in a phase 2 trial. The open-label, multicenter trial enrolled patients whose disease had progressed after prior systemic therapy and evaluated oral monotherapy in a biomarker-selected population without a concurrent control arm.

The trial included an exploratory phase and a pivotal phase, and 110 patients received savolitinib across both parts. Those groups comprised 45 patients in the exploratory phase and 65 in the pivotal phase. Eligible patients had MET-amplified locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma after at least one prior systemic line. The pivotal phase required at least two prior systemic lines and MET gene copy number of at least 10. Savolitinib was given orally as monotherapy in a heavily treated, biomarker-enriched later-line population.

The primary endpoint was independent review committee-assessed objective response rate in the pivotal cohort. The reported 95% confidence interval for that estimate was 21.2% to 45.1%. Its lower bound exceeded the prespecified 15% benchmark that defined success for the single-arm efficacy analysis.

Safety findings were assessed across all 110 enrolled and treated patients rather than only the pivotal cohort. Grade 3 or higher treatment-related adverse events occurred in 38 patients, or 34.5% of the overall study population. One treatment-related death was reported, representing 0.9% of treated patients. Overall, the safety findings included grade 3 or higher toxicity in about one-third of patients and one fatal treatment-related event.