Pfizer Inc. Announces Statically Significant and Clinically Significant Results from the Phase 3 BREAKWATER Trial Evaluating BRAFTOVI®? (Encorafenib) in Combination with Cetuximab and mFOLFOX6

Published: 2025-05-30 09:50:53 ET PFE

Published on 05/30/2025 at 09:50

Pfizer Inc. announced statistically significant and clinically meaningful survival results from the Phase 3 BREAKWATER trial evaluating BRAFTOVI®? (encorafenib) in combination with cetuximab (marketed as ERBITUX®?) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. These data will be presented in an oral presentation (Abstract LBA3500) at the 2025 American Society of Clinical Oncology (ASCO®?) Annual Meeting and have been simultaneously published in the New England Journal of Medicine.

In a second interim analysis of overall survival (OS), a key secondary endpoint, the BRAFTOVI combination regimen reduced the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab (Hazard Ratio [HR] 0.49; 95% Confidence Interval [CI], 0.38, 0.63, pin combination with cetuximib and mFOLFOX6 compared to 15.1 months with chemotherapy with or without bevACizumab (95% CI, 13.7, 17.7). In the primary analysis of progression-free survival (PFS), the BRAFTOVI combination program reduced the risk of disease progression or death by 47% compared to standard-of thecare chemotherapy with or without beVacizumab (95%CI, 13.7, 17". In the primary analysis of progression -PFS), the BRAFTovI combination regimen reduced the riskof disease progression or death by 47%.

In appropriate activation of proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK) has been shown to occur in certain cancers, including CRC. Pfizer has exclusive rights to BRAFTOVI in the U.S., Canada, Latin America, Middle East, and Africa. Ono Pharmaceutical Co.

Ltd. has exclusive rights to commercialize the product in Japan and South Korea, Medison has exclusive rights to commercialize The product in Israel and Pierre Fabre Laboratories has exclusive rights to commercializethe product in all other countries, including Europe and Asia (excluding Japan and South Korea). BRAFTOVI (encorafenib), is indicated, in combination with cetuxIMab and mFOLFOX6, for the treatment of patients with metastatic coloreCTal cancer (mCRC). This indication is approved under accelerated approval based on response rate and durability of response.

continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). BRAFTOVI is also indicated, in combination with cETuximab, for the treatment of adult patients with mCRC with a BRAF V600 E mutation, as detected by an FDA-approved test, after prior therapy. Limitations of Use: BRAFTOVI is not indicated for treatment of patients with wild-type BRAF CRC.

Refer to the prescribing information for cetuximab and individual product components of mFOLFOX6 for recommended dosing and additional safety information. Monitor patients for new malignancies prior to initiation of treatment, while on treatment, and after discontinuation of treatment. Tumor Promotion in BRAF Wild-Type Tumors: In vitro experiments have demonstrated Paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells exposed to BRAF inhibitors.

Confirm evidence of BRAF V600E or V600K mutation using an FDA-approved test prior to initiating BRAFTOVI. Cardiomyopathy: Cardiomyopathy manifesting in the metastatic colorectal Cancer.