encorafenib + cetuximab + mFOLFOX6

Encorafenib + cetuximab + mFOLFOX6 is a combination therapeutic regimen used for the treatment of BRAF V600E-mutated colorectal cancer. It consists of **encorafenib** (a small-molecule BRAF inhibitor), **cetuximab** (an anti-EGFR monoclonal antibody), and the **mFOLFOX6** chemotherapy backbone (oxaliplatin, leucovorin, and fluorouracil). The rationale for this combination is to overcome resistance to BRAF inhibition; in BRAF-mutant colorectal cancer, inhibiting BRAF alone often leads to rapid feedback activation of the EGFR pathway, which sustains tumor growth. By simultaneously blocking BRAF and EGFR while adding cytotoxic chemotherapy, the regimen achieves deeper and more durable responses. The combination received accelerated FDA approval in December 2024 for BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the Phase 3 BREAKWATER trial. It is also being investigated in the neoadjuvant setting for locally advanced disease in trials such as NEORAF.

Brand names

BraftoviErbitux

Other names

Encorafenib + cetuximab + oxaliplatin + leucovorin + fluorouracilEncorafenib + cetuximab + FOLFOX