Multicenter, multi-cohort phase 2 study of vebreltinib in MET amplification-driven non-small cell lung cancer

Vebreltinib is a potent and selective MET inhibitor. The multi-cohort phase 2 KUNPENG trial, at 17 centers in China, evaluated vebreltinib in patients with MET amplification-driven locally advanced or metastatic non-small cell lung cancer (gene copy number of six or higher). Patients were eligible if they were MET inhibitor-naïve, aged 18 years or older, and progressed after previous standard chemotherapy of were ineligible for chemotherapy (cohort 2) or refused chemotherapy (cohort 3). Results for cohorts 2 and 3 have now been published. Patients received vebreltinib 200 mg orally twice daily until disease progression or intolerable toxicity. Primary endpoint was centrally blinded assessed objective response rate. Among 86 patients (30 chemotherapy-treated and 56 untreated) with a median follow-up of 18.6 months (IQR 15.7-37.3), 42 had partial response, resulting in an ORR of 48.8% (95% CI 38.3-59.4). The incidence of grade 3 or worse treatment-related adverse events was 31%. Serious adverse events related to treatment were reported by 19%, and 11 treatment-emergent adverse events leading to death occurred, of which one patients died of abnormal liver function possibly related to vebreltinib treatment. The authors conclude that vebreltinib showed antitumor activity in patients with MET amplification-driven advanced NSCLC.