Phase IbII Study of Vebreltinib and Furmonertinib Treatment for Advanced or Metastatic Non-Small Cell Lung Cancer with c-Met Amplification After EGFR-TKI Therapy Failure

What this Trial Is About

Researchers are evaluating the combination of vebreltinib and furmonertinib in patients with locally advanced or metastatic non-small cell lung cancer NSCLC who have c-Met amplification and have experienced failure of prior EGFR-TKI treatment. This study includes both a Phase Ib and a Phase II clinical trial. The Phase Ib study aims to determine the maximum tolerated dose MTD, dose-limiting toxicities DLT, and the recommended Phase II dose RP2D of vebreltinib combined with furmonertinib. The Phase II study will assess the efficacy of this combination by measuring outcomes such as overall response rate ORR and progression-free survival PFS. The Phase Ib study involves two stages dose escalation and dose expansion. Dose escalation uses a 33 design with vebreltinib doses of 100 mg, 150 mg, and 200 mg taken twice daily, combined with furmonertinib at 80 mg once daily. Dose escalation decisions depend on the occurrence of DLTs within 28 days. The dose expansion stage will enroll approximately 10 additional patients per selected dose level to confirm safety and determine the recommended dose for Phase II. In the Phase II study, participants will receive the recommended dose of vebreltinib twice daily along with furmonertinib 80 mg once daily until disease progression or intolerable side effects occur. During the study, participants will undergo various assessments including tumor evaluations based on RECIST v1.1 criteria, laboratory tests, and safety monitoring. The primary outcomes include incidence of DLTs, determination of MTD and RP2D in Phase Ib, and ORR in Phase II. Secondary outcomes include progression-free survival, duration of response, disease control rate, overall survival, adverse events, and health-related quality of life. The total observation period for some outcomes extends up to five years, with active treatment continuing until disease progression or unacceptable toxicity.

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