FDA

Braftovi regimen gains full FDA approval for advanced colorectal cancer

February 27, 2026

On February 24, 2026, FDA granted traditional approval to Braftovi (encorafenib) in combination with cetuximab and fluorouracil‑based chemotherapy for adults with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, detected using an FDA‑authorized test.

Efficacy

The BREAKWATER trial (NCT04607421) was a randomized, active‑controlled, open‑label, multicenter study evaluating first‑line therapy for patients with treatment‑naïve, BRAF V600E–mutated metastatic colorectal cancer, identified using the therascreen BRAF V600E RGQ PCR assay. The Phase 3 design initially included three arms:

• encorafenib + cetuximab (Arm A);
• encorafenib + cetuximab + mFOLFOX6 (Arm B);
• investigator’s‑choice chemotherapy (mFOLFOX6, FOLFOXIRI, or CAPOX) with or without bevacizumab (Arm C).

The protocol was later amended to restrict randomization to Arm B vs Arm C (1:1) and to add Cohort 3, comparing encorafenib + cetuximab + FOLFIRI (Arm D) with FOLFIRI ± bevacizumab (Arm E). Treatment continued until progression, unacceptable toxicity, or discontinuation.

In the main Phase 3 comparison, 236 patients received Arm B and 243 received Arm C. Arm B demonstrated a clinically meaningful improvement in progression‑free survival (PFS): median PFS was 12.8 months vs 7.1 months for Arm C (hazard ratio [HR], 0.53; p<0.0001). Median overall survival was also significantly prolonged (30.3 vs 15.1 months; HR, 0.49; p<0.0001). The objective response rate (first 110 patients per arm, BICR) was 61% with Arm B versus 40% with Arm C (p=0.0008).

In Cohort 3, 73 patients were randomized to Arm D and 74 to Arm E. ORR, the primary endpoint, was 64% for Arm D compared with 39% for Arm E (p=0.0011), supporting the efficacy of encorafenib‑based triplet therapy with either FOLFOX or FOLFIRI backbones.

Safety

The prescribing information includes warnings and precautions for new primary malignancies (cutaneous and noncutaneous), tumor promotion in BRAF–wild-type tumors, cardiomyopathy, hepatotoxicity, hemorrhage, uveitis, QT prolongation, and embryo-fetal toxicity.

Recommended dose

The recommended dosage of Braftovi is 300 mg (four 75 mg capsules) orally once daily in combination with cetuximab and mFOLFOX6 or in combination with cetuximab and FOLFIRI until disease progression or unacceptable toxicity.

Source:

(2026, February 24). FDA. FDA grants traditional approval to encorafenib for metastatic colorectal cancer with a BRAF V600E mutation. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-encorafenib-metastatic-colorectal-cancer-braf-v600e-mutation

Braftovi (encorafinib) [package insert]. Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/210496s021lbl.pdf Revised February 2026. Accessed February 26, 2026.