Less than two months after an accelerated approval from the FDA, a drug combination featuring Pfizer’s Braftovi has turned in positive trial results that could set it up for a full approval.
The drug cocktail includes Braftovi, Eli Lilly’s Erbitux and the chemo regimen mFOLFOX6. In patients with metastatic colorectal cancer harboring a BRAF V600E mutation, the combo not only staved off disease progression but it also significantly extended patients’ lives compared with standard chemotherapy, with or without bevacizumab, the phase 3 Breakwater study has found.
The benefits on both the progression-free survival and overall survival metrics were “statistically significant and clinically meaningful,” Pfizer said in a Monday press release.
The Braftovi-Erbitux-chemo combo in December won an FDA accelerated approval based on tumor shrinkage data from the same trial. Now, Pfizer plans to use the updated analysis to seek a full approval.
BRAF V600E-mutated colorectal cancer represents a niche indication, accounting for an estimated 8% to 12% of metastatic colorectal cancer cases. The Braftovi-Erbitux-chemo regimen is the first treatment approved for first-line use in this tumor type.
The latest Breakwater results “have the potential to be practice-changing for this patient population that has historically had limited treatment options and poor outcomes,” Roger Dansey, M.D., Pfizer’s interim chief oncology officer, said in a statement.
It was largely expected that Breakwater would meet its overall survival goal, a key secondary endpoint. At an interim analysis with a data cutoff in December of 2023, the Braftovi-containing arm already showed a preliminary 53% lower risk of death compared with standard of care. Although that outcome was not statistically significant at the time, the advantage appeared to be stabilizing by the readout, according to data presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancer Symposium a few days ago.
The success of Breakwater is not just a win for Pfizer but one for the FDA as well. As Pfizer duly noted, the approval of the Braftovi combo in December was among the first granted under the FDA’s Project FrontRunner, which was designed to facilitate the development of new cancer drugs for earlier lines of therapy.
Under this initiative, the FDA proposed a one-trial approach to support both the accelerated approval and regular approval. While the traditional method typically involves a single-arm trial in a late-line setting to facilitate a conditional nod and a separate randomized study in an earlier treatment setting for a full go-ahead, the FDA now encourages companies to conduct one phase 3 study and rely on an interim analysis to pursue an accelerated approval first.
Breakwater could serve as an example that this model works. When the FDA handed out the accelerated approval, the Breakwater trial had met one of its dual primary endpoints, linking the Braftovi regimen to a higher 60.9% tumor response rate versus 40% for the control arm. At the same time, the interim overall survival signal also provided the FDA extra comfort.