Abstract
BACKGROUND: While the triplet combination of encorafenib (ENCO), binimetinib (BINI), plus cetuximab (CET) yielded a higher response rate compared with the doublet combination of ENCO plus CET, no significant survival benefits of the triplet combination were observed in patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC), according to the BEACON CRC study. Although ENCO plus CET is the standard second-line therapy, poor prognoses are expected after disease progression. TRIAL DESIGN: BAYONET is a single-arm multicenter phase II trial designed to evaluate the efficacy and safety of staged combination with ENCO, BINI, plus CET for patients with BRAF V600E-mutant mCRC refractory to ENCO plus CET. The main inclusion criteria are as follows: RAS wild-type/BRAF V600E-mutant mCRC; <4 weeks from the last administration of previous ENCO or CET; no administration of other systemic therapy after refractoriness to ENCO plus CET; and complete response, partial response, or ≥4 months of stable disease in the previous ENCO plus CET. The primary endpoint of this trial is the 12-week progression-free survival rate. As a translational analysis, circulating tumor DNA for next-generation sequencing using Guardant360 is collected at two time points (before and after study treatment) to investigate potential mechanisms of resistance.