Pfizer Inc. has reported positive topline progression-free survival (PFS) results from Cohort 3 of the Phase 3 BREAKWATER trial evaluating its BRAF inhibitor BRAFTOVI (encorafenib) in combination with cetuximab, marketed as ERBITUX, and FOLFIRI chemotherapy in patients with previously untreated metastatic colorectal cancer (mCRC) harboring a BRAF V600E mutation.
The company said the regimen demonstrated a statistically significant and clinically meaningful improvement in PFS compared with treatment using FOLFIRI with or without bevacizumab, as assessed by blinded independent central review. Overall survival, a secondary endpoint, also showed a clinically meaningful prolongation in patients treated with the BRAFTOVI-based combination.
Cohort 3’s primary endpoint was objective response rate (ORR) by blinded independent central review. Positive ORR data from this cohort were recently presented at the 2026 American Society of Clinical Oncology Gastrointestinal Cancers Symposium.
The newly reported PFS findings build on those response data and further support the potential role of this targeted combination in the first-line treatment setting for patients with BRAF V600E-mutant mCRC. At the time of analysis, the safety profile of BRAFTOVI in combination with cetuximab and FOLFIRI was consistent with the known profiles of the individual agents, and no new safety signals were identified.
The triplet regimen remains investigational and is not currently approved. Detailed results from Cohort 3 are expected to be presented at an upcoming medical meeting and will be shared with the U.S. Food and Drug Administration to support potential approval in this molecularly defined patient population.
In December 2024, BRAFTOVI in combination with cetuximab and mFOLFOX6 received accelerated approval from the FDA for previously untreated patients with BRAF V600E-mutant mCRC based on statistically significant and clinically meaningful improvements in confirmed ORR. Continued approval for that indication is contingent upon verification of clinical benefit.
The latest findings from BREAKWATER may further strengthen the evidence base for BRAFTOVI-based regimens in this high-risk subgroup.
