Pfizer today reported data from Cohort 3 of the pivotal BREAKWATER trial evaluating BRAFTOVI® (encorafenib) in combination with cetuximab and FOLFIRI in 97 patients with previously untreated metastatic colorectal cancer harboring the BRAF V600E mutation. The triplet regimen achieved an objective response rate of 58%, compared with a historical benchmark of 26% for standard chemotherapy, and produced a median progression-free survival of 7.4 months versus 4.5 months in retrospective controls. Duration of response averaged 9.2 months, and 23% of responders remained on treatment beyond one year. Safety findings were consistent with known profiles for each agent: grade 3–4 adverse events occurred in 42% of patients, the most common being neutropenia (18%), diarrhea (12%) and fatigue (10%), with 7% discontinuing for treatment-related toxicity. These results support the planned regulatory submissions for the regimen as a first-line option in this high-risk population and mark a significant advancement over dual-therapy approaches.

Based on the positive Cohort 3 results, Pfizer intends to engage with regulatory authorities in the coming quarter to discuss label expansion in North America, Europe and Asia-Pacific. The company has allocated additional manufacturing capacity to support up to 15,000 patient treatment courses annually and plans to initiate a confirmatory Phase III study in 2026 comparing the triplet regimen directly against FOLFIRI plus cetuximab. Pfizer’s global commercial teams are preparing educational programs targeting oncologists at over 200 cancer centers worldwide, anticipating launch in late 2027 subject to approval. The program underscores Pfizer’s commitment to personalized oncology solutions and leverages more than 15 years of clinical development expertise in BRAF-driven cancers.