NCT07087223

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

The Open-Label, Multicenter Phase Ib/II Clinical Study Evaluating the Safety and Efficacy of Vebreltinib Combined With Furmonertinib in Locally Advanced or Metastatic NSCLC Patients With c-Met Amplification After EGFR-TKI Failure

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 42 (estimated)
• Sponsor: Peking University Cancer Hospital & Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of phase Ib study was to evaluate efficacy and tolerability of the combination of vebreltinib and furmonertinib in patients with locally advanced or metastatic non-small cell lung cancer with c-met amplification after failure of EGFR-TKI treatment; to determine the maximum tolerated dose (MTD), and to evaluate the dose-limiting toxicity (DLT) and (recommended Phase 2 dose) RP2D of vebreltinib with furmonertinib. The goal of phase II study was to evaluate efficacy \[overall response rate (ORR), progression-free survival (PFS), and so on\] of vebreltinib and furmonertinib in patients with locally advanced or metastatic non-small cell lung cancer with c-met amplification after failure of EGFR-TKI treatment.

Detailed description

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.

Conditions

• Non Small Cell Lung Cancer NSCLC

Interventions

Type	Name	Description
DRUG	Vebreltinib combined with Furmonertinib	Vebreltinib 100mg/1500mg/200mg oral twice daily combined with Furmonertinib 80mg oral once daily
DRUG	Vebreltinib combined with Furmonertinib	Vebreltinib 100mg/1500mg/200mg oral twice daily combined with Furmonertinib 80mg oral once daily. Based on the safety data from the completed dose cohorts, the investigators will involve the selection of 1-2 dose cohorts for further study. Approximately 10 additional subjects will be enrolled in the selected dose expansion cohort to determine the recommended dose for Phase II clinical trials.
DRUG	Vebreltinib combined with Furmonertinib	RP2D of Vebreltinib as determined during Phase Ib oral twice daily combined with Furmonertinib 80mg oral once daily

Timeline

• Start date: 2025-04-08
• Primary completion: 2027-04-01
• Completion: 2028-04-01
• First posted: 2025-07-25
• Last updated: 2025-07-25

Locations

12 sites across 1 country: China