Phase Ib/II Study of Vebreltinib With Furmonertinib in NSCLC Patients With c-Met Amplification After EGFR-TKI Failure

Phase Ib study uses 3+3 clinical design. The Phase Ib clinical trial is designed to explore the dosing of vebreltinib, consisting of two stages: dose escalation and dose expansion. The dose escalation stage follows a 3+3 design with three escalating dose levels (100 mg BID, 150 mg BID, 200 mg BID). Each dose cohort enrolls 3 patients. If no DLTs are observed in the first 3 patients within 28 days, the dose is escalated to the next cohort. If more than 1 DLT is observed in the first 3 patients within 28 days, that dose level is deemed non-tolerable. If 1 DLT is observed in the first 3 patients within 28 days, an additional 3 patients are enrolled at that dose level. If no DLTs are observed in the additional patients, dose escalation proceeds to the next cohort. If more than 1 DLT is observed among the additional patients (i.e., a total of 2 DLTs in the cohort), the previous dose level is determined to be the MTD. After completion of DLT assessment, the investigator decided whether to continue the treatment after the end of DLT assessment based on the subject 's tolerance and the safety profile of the dose group. The dose expansion phase, based on the safety data from the completed dose cohorts, will involve the selection of 1-2 dose cohorts by the investigators for further study. Approximately 10 additional subjects will be enrolled in each selected dose expansion cohort to determine the recommended dose for Phase II clinical trials. In the Phase II clinical study, the recommended Phase II dose of vebreltinib, determined from the Phase Ib study, will be combined with Furmonertinib to treat locally advanced or metastatic NSCLC with c-Met amplification in patients after failure of EGFR-TKI treatment. The study aims to evaluate the efficacy and safety of this combination, with an anticipated enrollment of 20 subjects. Participants will take vebreltinib (RP2D bid) and furmonertinib (80mg qd) until disease progression or undurable toxicity.