Combination Therapy for BRAF-V600E Metastatic CRCm

Study Design: The study adopts a multicenter, open-label, phase II design. Patients with metastatic CRC harboring the BRAF-V600E mutation, who have experienced disease progression after one or two prior chemotherapy regimens, are eligible for enrollment. The treatment regimen consists of daily oral encorafenib (300 mg), biweekly intravenous cetuximab (500 mg/m2), and biweekly intravenous bevacizumab (5 mg/kg). Treatment will be administered in 28-day cycles until disease progression, unacceptable toxicity, consent withdrawal, initiation of other anticancer therapy, or death. Secondary Objectives: Secondary objectives include evaluating the safety and tolerability of the combination therapy, assessing objective response rate, time to response, duration of response, overall survival, and patient-reported outcomes. Exploratory objectives involve evaluating potential biomarkers predictive of treatment response and resistance, as well as generating functional models to assess novel drug combinations targeting resistance mechanisms.