Pfizer has announced positive topline progression-free survival results from cohort 3, a separate randomized cohort of the pivotal BREAKWATER trial, evaluating encorafenib in combination with cetuximab and FOLFIRI (fluorouracil, leucovorin, and irinotecan) in patients with previously untreated metastatic colorectal cancer with a BRAF V600E mutation. The regimen demonstrated a statistically significant and clinically meaningful improvement in progression-free survival, a key secondary endpoint, as assessed by blinded independent central review compared to treatment with FOLFIRI with or without bevacizumab. Overall survival, a descriptive secondary endpoint, also showed clinically meaningful prolonged improvement with the encorafenib-based regimen.
“These results build on the positive objective response rate data we recently shared, providing further evidence of the meaningful benefit this [encorafenib]-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 [encorafenib] as a potentially practice-changing treatment option for patients and families facing this challenging diagnosis.”
The primary endpoint of this cohort of BREAKWATER was objective response rate by blinded independent central review. Positive objective response rate results were achieved and recently presented at the 2026 ASCO Gastrointestinal Cancers Symposium. At the time of the progression-free survival analysis, the safety profile of encorafenib in combination with cetuximab and FOLFIRI was consistent with the known profile of each regimen component and no new safety signals were identified.
Encorafenib in combination with cetuximab and FOLFIRI is an investigational regimen and is not currently approved. Detailed results from this cohort will be submitted for presentation at an upcoming medical meeting and shared with the U.S. Food and Drug Administration (FDA) to support potential approval for encorafenib in combination with cetuximab and FOLFIRI in patients with BRAF V600E–mutant metastatic colorectal cancer.
Encorafenib in combination with cetuximab and mFOLFOX6 received accelerated approval from the FDA in December 2024 for patients with BRAF V600E-mutant metastatic colorectal cancer based on a clinically meaningful and statistically significant improvement in confirmed objective response rate in treatment-naive patients, one of the study’s primary endpoints. Continued approval for this indication is contingent upon verification of clinical benefit.
