Pfizer Inc., a leading pharmaceutical company, announced on Monday promising results from their Phase 3 BREAKWATER study regarding BRAFTOVI (encorafenib) in a combination treatment for metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. This treatment regimen, which includes BRAFTOVI alongside cetuximab (sold as ERBITUX) and the chemotherapy regimen mFOLFOX6 (comprising fluorouracil, leucovorin, and oxaliplatin), demonstrated a notable and clinically substantial enhancement in progression-free survival (PFS) for patients involved in the study.
The PFS, a primary endpoint of the trial, was independently assessed by a blinded central review and showed significant improvement when compared to patients who were treated with chemotherapy, with or without the addition of bevacizumab. Additionally, the BRAFTOVI combination therapy exhibited statistically meaningful improvements in overall survival (OS), which is a crucial secondary endpoint of this trial.
BRAFTOVI is recognized as an oral small molecule kinase inhibitor that effectively targets the BRAF V600E mutation. Pfizer explained that the inappropriate activation of particular proteins within the MAPK signaling pathway (RAS-RAF-MEK-ERK) can be active in certain cancers, inclusive of colorectal cancer.
Further highlighting the drug's development path, the BRAFTOVI regimen received accelerated approval from the U.S. Food and Drug Administration in December 2024. This approval was based on a notable improvement in confirmed objective response rate (ORR), which was another dual primary endpoint of the study. The ORR findings were shared at the 2025 American Society of Clinical Oncology Gastrointestinal Cancer Symposium and were published in Nature Medicine that same January.
Commenting on the developments, Roger Dansey, Pfizer’s Chief Oncology Officer, stated, "The BRAFTOVI regimen is setting a new standard as the first approved targeted therapy accessible from the first-line treatment stage for patients with mCRC and a BRAF V600E mutation. We are eager to collaborate with health authorities globally to make this treatment available to more patients worldwide at the earliest opportunity."
The FDA's approval process for this regimen comes under Project FrontRunner, an initiative aimed at fast-tracking the development and approval of innovative cancer therapies for advanced or metastatic conditions.
Pfizer plans to present the latest findings to the FDA to secure full approval for the BRAFTOVI combination in treating patients with mCRC carrying a BRAF V600E mutation.
BRAFTOVI's commercial rights are region-specific: Pfizer holds rights in the U.S., Canada, Latin America, the Middle East, and Africa. In Japan and South Korea, the rights are exclusive to Ono Pharmaceutical Co., Ltd., Medison controls rights in Israel, and Pierre Fabre Laboratories holds rights for all other regions, including Europe and most of Asia (excluding Japan and South Korea).
As of pre-market trading on the NYSE, Pfizer's shares were valued at $26.31, reflecting a slight decrease of 0.79 percent.
