Efficacy data are assessed by blinded independent central review and will be shared at ASCO GI Cancers Symposium in 2026 (Abstract 13).

Pfizer emphasizes ongoing communication with plain-language summaries and outlines BREAKWATER’s design and patient arms, with completion anticipated in 2027.

Regulatory status remains investigational for the BRAFTOVI-cetuximab-FOLFIRI combination, while a related regimen with cetuximab and mFOLFOX6 has FDA accelerated approval from December 2024 for untreated BRAF V600E-mutant mCRC.

In BREAKWATER Cohort 3, Pfizer reports positive results for BRAFTOVI (encorafenib) plus cetuximab and FOLFIRI in previously untreated metastatic colorectal cancer with a BRAF V600E mutation.

The trial randomized 73 patients to the BRAFTOVI-cetuximab-FOLFIRI arm versus 74 to FOLFIRI (± bevacizumab) in a Phase 3, multicenter setting, with the primary endpoint of objective response rate (ORR) assessed by Blinded Independent Central Review and progression-free survival as a key secondary endpoint.

BREAKWATER is a Phase 3, open-label study evaluating BRAFTOVI with cetuximab, with or without chemotherapy backbones, and Cohort 3 specifically compares the BRAFTOVI-cetuximab-FOLFIRI combination to FOLFIRI ± bevacizumab.

Descriptive OS analyses indicate potential benefit for the BRAFTOVI combination, while the study continues toward its planned 2027 finish.

Safety guidance highlights risks including new primary malignancies, QT prolongation, hepatotoxicity, hemorrhage, uveitis, embryo-fetal toxicity, and interactions with CYP3A4 modulators or substrates, with dosing and monitoring recommendations provided.

Durability signals show 57.4% of responders in the BRAFTOVI arm maintaining responses for 6 months or longer, while median duration of response was not estimable for this group.

Overall survival data were descriptively analyzed, showing a hazard ratio around 0.49 with roughly 10 months of follow-up, and the trial is ongoing with completion expected in 2027.

An exploratory OS estimate yielded a hazard ratio near 0.49 (95% CI ~0.24–1.03) after about 10 months of follow-up, with ongoing study of BREAKWATER through 2027.

Safety in BREAKWATER aligns with known profiles of the drugs, with common adverse events like neuropathy, nausea, fatigue, rash, diarrhea, decreased appetite, vomiting, and some hemorrhage; about 8.5% discontinued BRAFTOVI due to an adverse reaction.