BREAKWATER — Encorafenib Plus Cetuximab With Chemotherapy in First-Line BRAF V600E-Mutant Metastatic Colorectal Cancer

Phase 3 · 2025 · Colorectal Cancer

Design

Randomized open-label to encorafenib plus cetuximab plus FOLFOX/FOLFIRI vs standard chemotherapy with or without bevacizumab.

Population

Previously untreated BRAF V600E-mutant metastatic colorectal cancer.

Primary Endpoint

objective response rate (ORR) and progression-free survival (PFS)

Key Result

First-line mFOLFOX6 cohort: median OS 30.3 vs 15.1 mo (HR 0.49, P<0.0001); median PFS 12.8 vs 7.1 mo (HR 0.53, P<0.0001); ORR 65.7% vs 37.4% — roughly doubling response and survival versus chemotherapy ± bevacizumab.

Guideline Impact

Supported first-line encorafenib plus cetuximab with chemotherapy for BRAF V600E-mutant metastatic colorectal cancer