FDA grants traditional approval to encorafenib for metastatic colorectal cancer with a BRAF V600E mutation
Regulatory approval: On Feb 24, 2026, the FDA granted traditional approval to encorafenib (Braftovi) in combination with cetuximab and fluorouracil-based chemotherapy for adults with metastatic colorectal cancer harboring a BRAF V600E mutation detected by an FDA-authorized test. The decision was supported by BREAKWATER, which showed improved PFS, OS, and ORR versus chemotherapy-based control regimens in treatment-naïve patients. Encorafenib previously received accelerated approval in 2024 in combination with cetuximab and mFOLFOX6.
FDA traditional approval: encorafenib for BRAF V600E–mutant metastatic CRC
Type: Regulatory approval
Date: 2026-02-24
Agency: FDA
The FDA granted traditional approval to encorafenib (Braftovi; Array BioPharma Inc., a subsidiary of Pfizer Inc.) in combination with cetuximab and fluorouracil-based chemotherapy for adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-authorized test. Encorafenib had received accelerated approval in 2024 in combination with cetuximab and mFOLFOX6 for metastatic CRC with a BRAF V600E mutation.
Evidence base (BREAKWATER; NCT04607421)
BREAKWATER is a randomized, active-controlled, open-label, multicenter trial in treatment-naïve, BRAF V600E mutation–positive metastatic CRC (Qiagen therascreen BRAF V600E RGQ PCR Kit).
Phase 3 portion: Arm B (encorafenib + cetuximab + mFOLFOX6; n=236) vs Arm C control regimens (n=243).
- Median PFS: 12.8 vs 7.1 months (HR 0.53; p<0.0001)
- Median OS: 30.3 vs 15.1 months (HR 0.49; p<0.0001)
- ORR: 61% vs 40% (p=0.0008)
Cohort 3: Arm D (encorafenib + cetuximab + FOLFIRI; n=73) vs Arm E (FOLFIRI ± bevacizumab; n=74). ORR: 64% vs 39% (p=0.0011).
Key warnings/precautions
Includes risks of new primary malignancies, tumor promotion in BRAF wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.