Vebreltinib in MET amplification-driven advanced non-small-cell lung cancer (KUNPENG): a single-arm, multi-cohort,...

MET amplification is recognised as a de novo driver alteration in non-small-cell lung cancer (NSCLC) but treatment responses with existing MET inhibitors remain largely unsatisfactory. We aimed to investigate the antitumour activity and safety of vebreltinib, a potent and highly selective MET inhibitor, in patients with MET amplification-driven NSCLC.

KUNPENG was a multicentre, multi-cohort, single-arm, phase 2 trial conducted across 17 hospitals in China, in patients with locally advanced or metastatic NSCLC with MET dysregulation. Patients were eligible if they were MET inhibitor-naive, aged 18 years or older with MET amplification-driven NSCLC (gene copy number of six or higher), and progressed after previous standard chemotherapy or were ineligible for chemotherapy (cohort 2) or refused chemotherapy (cohort 3). Patients received 200 mg vebreltinib orally twice daily until disease progression or intolerable toxicity. The primary endpoint was the objective response rate, assessed by a masked independent review committee in the full analysis set. The study was amended to merge cohorts 2 and 3 due to slow accrual and was closed to enrolment on Nov 14, 2023. This trial is registered with ClinicalTrials.gov (NCT04258033).

Between Jan 17, 2020, and Nov 14, 2023, 145 patients were enrolled; of these, 86 patients (30 chemotherapy-treated and 56 untreated) from cohorts 2 and 3 were included in the current analysis. The median age was 65 years (range 48-82; IQR 59-71), 77 (90%) patients were male, and nine (10%) were female. All patients were Chinese. 42 patients had partial response, resulting in an objective response rate of 48·8% (42 of 86; 95% CI 38·3-59·4) per masked independent review committee. The median follow-up was 18·6 months (IQR 15·7-37·3). The incidence of grade 3 or worse treatment-related adverse events was 31% (27 of 86), predominantly abnormal liver function terms reported by the investigators (eight [9%]). Serious adverse events related to treatment were reported by 16 (19%) patients. 11 treatment-emergent adverse events leading to death occurred, of which one patient died of abnormal liver function, which was possibly related to vebreltinib treatment.

Vebreltinib showed antitumour activity in patients with MET amplification-driven advanced NSCLC who had previously received chemotherapy or were chemotherapy-naive. Further research is needed to validate these findings.

Beijing Pearl Biotechnology and Avistone Biotechnology.