Pfizer’s Braftovi (encorafenib), in combination with Erbitux (cetuximab) and Folfiri (fluorouracil, leucovorin and irinotecan), has shown positive results in a new trial of patients with previously untreated metastatic colorectal cancer (mCRC) with a BRAF V600E mutation.
Braftovi is an oral small molecule kinase inhibitor designed to specifically target BRAF V600E.
Results from cohort 3 of the BREAKWATER trial showed that the Braftovi-Erbitux-Folfiri combination regimen demonstrated a clinically meaningful and statistically significant response rate in this patient group, compared with patients receiving Folfiri with or without bevacizumab. Within the Braftovi combination treatment arm, 57.4% of patients saw a response lasting six months or longer, compared with 34.5% of patients receiving Folfiri with or without bevacizumab.
The Braftovi combination regimen demonstrated a safety profile consistent with each drug’s established safety profile, and no new safety signals were identified by the trial. The BREAKWATER trial is ongoing and is expected to be completed in 2027.
CRC is the third most common cancer worldwide and the second leading cause of cancer-related deaths. Around 154,720 people in the US are expected to be diagnosed with CRC in 2025, and around 53,000 people in the US die from the disease annually. Additionally, 20% of all CRC patients see their disease metastasise or spread to other areas of the body.
Approximately 8-12% of people with mCRC develop BRAF mutations, with BRAF V600E being the most common. Mortality risk in CRC patients with BRAF V600E mutation is over double that of patients without known mutation. Prior to December 2024 there were no approved biomarker-driven treatments for previously untreated mCRC with BRAF V600E mutations.
Scott Kopetz, Professor and Deputy Chair of Gastrointestinal Medical Oncology at the University of Texas MD Anderson Cancer Center and co-principal investigator of the BREAKWATER trial, said: “These results represent a great advance for patients with BRAF V600E-mutant mCRC. We’ve seen this approach significantly increase the response compared to Folfiri with or without bevacizumab, and these responses were rapid and durable.
“The trial supports the potential for another chemotherapy backbone option that may be paired with encorafenib plus cetuximab in this patient population.”
Jeff Legos, chief oncology officer at Pfizer, added: “These results underscore the potential of Braftovi as a standard of care for patients with this aggressive cancer.”
The data will be presented in an oral presentation at the 2026 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium.