Pfizer’s BRAFTOVI Combo Boosts Survival in Phase 3 BREAKWATER Trial

Pfizer Inc. announced positive topline results from the progression-free survival (PFS) analysis of the Phase 3 BREAKWATER study of BRAFTOVI (encorafenib) in combination with cetuximab (marketed as ERBITUX ) and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) harboring a BRAF V600E mutation. The trial showed a statistically significant and clinically meaningful improvement in PFS, one of its dual primary endpoints, as assessed by blinded independent central review (BICR) compared to patients receiving chemotherapy with or without bevacizumab. Further, the BRAFTOVI combination regimen demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), a key secondary endpoint in the trial.

“We are extremely pleased with the clinically meaningful progression-free survival and overall survival results from the BREAKWATER study, which have the potential to be practice-changing for this patient population that has historically had limited treatment options and poor outcomes,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “The BRAFTOVI regimen is emerging as a new standard of care as the first targeted therapy approved for use as early as first-line for patients with mCRC with a BRAF V600E mutation. We look forward to discussing these data with global health authorities to bring this treatment to more patients around the world, as soon as possible.”

The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for treatment-naïve patients with BRAFV600E -mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed objective response rate (ORR), the study’s other dual primary endpoint. The ORR results were presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO GI) and were simultaneously published in Nature Medicine in January 2025.

At the time of the ORR analysis, the safety profile of BRAFTOVI in combination with cetuximab and mFOLFOX6 continued to be consistent with the known safety profile of each respective agent. No new safety signals were identified. Detailed results from this analysis will be submitted for presentation at an upcoming medical meeting.

The approval of the BRAFTOVI combination regimen was among the first in the industry to be conducted under the FDA’s Project FrontRunner, which seeks to support the development and approval of new cancer drugs for advanced or metastatic disease. Pfizer will share these latest results with the FDA to potentially support full approval for BRAFTOVI in combination with cetuximab and mFOLFOX6 in patients with mCRC with a BRAF V600E mutation. The BREAKWATER data are also being discussed with other regulatory authorities around the world to support potential additional license applications for the BRAFTOVI combination regimen in this indication.