Pfizer Inc. recently disclosed detailed results from Cohort 3 of the Phase 3 BREAKWATER clinical trial, which investigates the efficacy of various regimens for patients diagnosed with previously untreated BRAF V600E-mutant metastatic colorectal cancer (mCRC). The trial compares the performance of Braftovi (encorafenib) paired with cetuximab, administered alongside chemotherapy options mFOLFOX6 or FOLFIRI, against the established standard-of-care chemotherapy treatments.
The focal point of this analysis was the combination of Braftovi, cetuximab, and the FOLFIRI chemotherapy backbone. Findings indicate a robust and significant improvement in the confirmed objective response rate (ORR) for this triplet therapy when compared to the control group receiving FOLFIRI alone or FOLFIRI combined with bevacizumab (Avastin).
Specifically, the confirmed ORR reached 64.4% in the cohort treated with Braftovi plus cetuximab and FOLFIRI, markedly higher than the 39.2% ORR recorded in patients treated with standard-of-care regimens. The statistical evaluation highlights a strong association with an odds ratio of 2.76 and a p-value of 0.001, reinforcing the clinical meaningfulness of these outcomes.
Within oncological clinical trials, the confirmed ORR represents the proportion of patients who experience measurable tumor shrinkage, an effect verified by a subsequent imaging assessment conducted after a minimum interval—customarily four weeks—to establish the durability of the response.
Additional data presented at the 2026 American Society of Clinical Oncology Gastrointestinal (ASCO GI) Cancers Symposium emphasize durability aspects. Although the median duration of response was not estimable at the time of reporting for either the Braftovi combination or comparator treatments, more than half (57.4%) of patients on the Braftovi, cetuximab, and FOLFIRI regimen sustained a response lasting six months or longer. This compares positively against a 34.5% six-month response rate observed within the FOLFIRI with or without bevacizumab treatment arms.
Overall survival (OS) data are being examined descriptively as the trial remains ongoing, with an estimated completion date anticipated in 2027. These survival data are crucial yet currently immature, reflecting the need for continued follow-up to confirm long-term benefits.
Braftovi’s use in combination with cetuximab and mFOLFOX6 received accelerated approval by the U.S. Food and Drug Administration in December 2024, specifically targeting patients with BRAF V600E-mutant metastatic colorectal cancer. This regulatory action was granted on the basis of demonstrated improvement in confirmed ORR among treatment-naïve patients, satisfying one of the primary endpoints of the evaluated studies.
It is important to note that the continued regulatory approval for this indication relies on further validation of clinical benefits beyond the initial response rates, emphasizing the necessity for durable outcomes and survival advantages.
Separately, Pfizer reported in December 2025 the comprehensive Phase 3 HER2CLIMB-05 trial results for Tukysa (tucatinib) used as an investigational first-line maintenance therapy following induction with chemotherapy for patients with HER2-positive metastatic breast cancer. Although distinct from the colorectal cancer data, this study demonstrated a 35.9% reduction in risk of disease progression or death when Tukysa was administered alongside trastuzumab and pertuzumab, compared to placebo with the same targeted therapy backbone.
Following these disclosures, Pfizer’s share price experienced a slight decline, trading at $25.41 and down 0.26% as captured by Benzinga Pro data on the Monday following the announcement.