Braftovi (encorafenib) regimen improves progression-free survival in metastatic colorectal cancer – Pfizer

Pfizer Inc. announced positive topline progression-free (PFS) survival results from Cohort 3, a separate randomized cohort of the pivotal BREAKWATER trial, evaluating  Braftovi (encorafenib) in combination with cetuximab (Erbitux) and FOLFIRI (fluorouracil, leucovorin, and irinotecan) in patients with previously untreated metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. The Braftovi regimen demonstrated a statistically significant and clinically meaningful improvement in PFS, a key secondary endpoint, as assessed by blinded independent central review (BICR) compared to treatment with FOLFIRI with or without bevacizumab. Overall survival (OS), a descriptive secondary endpoint, also showed clinically meaningful prolonged improvement with the Braftovir egimen.

The primary endpoint of this cohort of BREAKWATER was objective response rate (ORR) by BICR. Positive ORR results were achieved and recently presented at the 2026 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium. At the time of the PFS analysis, the safety profile of Braftovi  in combination with cetuximab and FOLFIRI was consistent with the known profile of each regimen component and no new safety signals were identified.

Detailed results from this cohort will be submitted for presentation at an upcoming medical meeting and shared with the FDA to support potential approval for Braftovi in combination with cetuximab and FOLFIRI in patients with BRAF V600E-mutant mCRC.

“These results build on the positive objective response rate data we recently shared, providing further evidence of the meaningful benefit this BRAFTOVI-based targeted approach may offer patients with BRAF V600E–mutant metastatic colorectal cancer,” said Jeff Legos, Chief Oncology Officer, Pfizer. “The combination of significant responses and now improvement in progression‑free survival underscores the potential of BRAFTOVI as a potentially practice-changing treatment option for patients and families facing this challenging diagnosis.”

BREAKWATER is a Phase III, randomized, active-controlled, open-label, multicenter trial of Braftovi  with cetuximab, alone or in combination with chemotherapy (mFOLFOX6 or FOLFIRI) in participants with previously untreated BRAF V600E-mutant mCRC (NCT04607421). Patients were randomized to receive Braftovi  300 mg orally once daily in combination with cetuximab (discontinued after randomization of 158 patients), Braftovi  300 mg orally once daily in combination with cetuximab and mFOLFOX6 (n=236) or mFOLFOX6, FOLFOXIRI, or CAPOX, with or without bevacizumab (control arm) (n=243). The dual primary endpoints for these study groups are ORR and PFS as assessed by BICR. OS is a key secondary endpoint. In Cohort 3, patients were randomized to receive Braftovi 300 mg orally once daily in combination with cetuximab and FOLFIRI (n=73) or FOLFIRI, with or without bevacizumab (control-arm) (n=74). The primary endpoint of Cohort 3 is ORR as assessed by BICR. PFS is a key secondary endpoint; OS is a secondary endpoint.