Encorafenib

Pfizer has announced that its Braftovi (encorafenib) regimen significantly improved both progression-free and overall survival in a late-stage colorectal cancer (CRC) study. The ongoing phase 3 BREAKWATER trial has been evaluating the drug in combination with Eli Lilly/Merck KGaA’s Erbitux (cetuximab) and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) in patients with previously untreated BRAF V600E-mutant metastatic CRC. The Braftovi regimen demonstrated statistically significant and clinically meaningful improvements in the dual primary endpoint of progression-free survival and the key secondary endpoint of overall survival compared chemotherapy with or without bevacizumab. Approximately 154,270 people are expected to be diagnosed with cancer of the colon or rectum in the US this year. BRAF mutations are estimated to occur in up to 12% of those with metastatic cases of the disease and are associated with a poor prognosis. Braftovi is an oral small molecule kinase inhibitor designed to target the most common BRAF mutation, BRAF V600E, which more than doubles patients’ risk of death compared to those with no known mutation present. The drug was granted accelerated approval by the US Food and Drug Administration (FDA) in December in combination with Erbitux and mFOLFOX6 for treatment-naïve patients with BRAF V600E-mutant metastatic CRC based on a clinically meaningful and statistically significant improvement in confirmed objective response rate, BREAKWATER’s other dual primary endpoint. Pfizer said it will now be sharing the new trial results with the FDA to support the potential conversion to full approval for the combination in this indication, adding that the data is also being discussed with other regulatory authorities globally. Pfizer’s chief oncology officer, Roger Dansey, said: “We are extremely pleased with the clinically meaningful progression-free survival and overall survival results from the BREAKWATER study, which have the potential to be practice-changing for this patient population that has historically had limited treatment options and poor outcomes. “The Braftovi regimen is emerging as a new standard of care as the first targeted therapy approved for use as early as first-line for patients with metastatic CRC with a BRAF V600E mutation. We look forward to discussing this data with global health authorities to bring this treatment to more patients around the world, as soon as possible.” Pfizer has exclusive rights to Braftovi in the US, Canada, Latin America, the Middle East and Africa, while licences are also held by Ono Pharmaceutical, Medison and Pierre Fabre.

NEW YORK, NY, USA I February 03, 2025 I Pfizer Inc. (NYSE: PFE) today announced positive topline results from the progression-free survival (PFS) analysis of the Phase 3 BREAKWATER study of BRAFTOVI ® (encorafenib) in combination with cetuximab (marketed as ERBITUX ® ) and mFOLFOX6 (fluorouracil, leucovorin and oxaliplatin) in patients with metastatic colorectal cancer (mCRC) harboring a BRAF V600E mutation. The trial showed a statistically significant and clinically meaningful improvement in PFS, one of its dual primary endpoints, as assessed by blinded independent central review (BICR) compared to patients receiving chemotherapy with or without bevacizumab. Further, the BRAFTOVI combination regimen demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS), a key secondary endpoint in the trial. “We are extremely pleased with the clinically meaningful progression-free survival and overall survival results from the BREAKWATER study, which have the potential to be practice-changing for this patient population that has historically had limited treatment options and poor outcomes,” said Roger Dansey, M.D., Chief Oncology Officer, Pfizer. “The BRAFTOVI regimen is emerging as a new standard of care as the first targeted therapy approved for use as early as first-line for patients with mCRC with a BRAF V600E mutation. We look forward to discussing these data with global health authorities to bring this treatment to more patients around the world, as soon as possible.” The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for treatment-naïve patients with BRAF V600E -mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed objective response rate (ORR), the study’s other dual primary endpoint. The ORR results were presented at the 2025 American Society of Clinical Oncology Gastrointestinal Cancer Symposium (ASCO GI) and were simultaneously published in Nature Medicine in January 2025. At the time of the ORR analysis, the safety profile of BRAFTOVI in combination with cetuximab and mFOLFOX6 continued to be consistent with the known safety profile of each respective agent. No new safety signals were identified. Detailed results from this analysis will be submitted for presentation at an upcoming medical meeting. The approval of the BRAFTOVI combination regimen was among the first in the industry to be conducted under the FDA’s Project FrontRunner, which seeks to support the development and approval of new cancer drugs for advanced or metastatic disease. Pfizer will share these latest results with the FDA to potentially support full approval for BRAFTOVI in combination with cetuximab and mFOLFOX6 in patients with mCRC with a BRAF V600E mutation. The BREAKWATER data are also being discussed with other regulatory authorities around the world to support potential additional license applications for the BRAFTOVI combination regimen in this indication. About BREAKWATER BREAKWATER is a Phase 3, randomized, active-controlled, open-label, multicenter trial of BRAFTOVI with cetuximab, alone or in combination with mFOLFOX6 in participants with previously untreated BRAF V600E-mutant metastatic CRC. Patients were randomized to receive BRAFTOVI 300 mg orally once daily in combination with cetuximab (discontinued after randomization of 158 patients), BRAFTOVI 300 mg orally once daily in combination with cetuximab and mFOLFOX6 (n=236) or mFOLFOX6, FOLFOXIRI, or CAPOX each with or without bevacizumab (control-arm) (n=243). The dual primary endpoints are ORR, which was met at the time of analysis, and progression-free survival (PFS) as assessed by blinded independent central review (BICR). Overall survival is a key secondary endpoint. About Colorectal Cancer (CRC) CRC is the third most common type of cancer in the world, with approximately 1.8 million new diagnoses in 2022. 1 It is the second leading cause of cancer-related deaths. 2 Overall, the lifetime risk of developing CRC is about 1 in 24 for men and 1 in 26 for women. 2 In the U.S. alone, an estimated 154,270 people will be diagnosed with cancer of the colon or rectum in 2025, and approximately 53,000 are estimated to die from the disease each year. 3 For 20% of those diagnosed with CRC, the disease has metastasized, or spread, making it harder to treat, and up to 50% of patients with localized disease eventually develop metastases. 4 BRAF mutations are estimated to occur in 8-12% of people with mCRC and represent a poor prognosis for these patients. 5 The BRAF V600E mutation is the most common BRAF mutation and the risk of mortality in CRC patients with the BRAF V600E mutation is more than double that of patients with no known mutation present. 5,6 Despite the high unmet need in BRAF V600E -mutant mCRC, prior to December 20, 2024 there were no approved biomarker-driven therapies specifically indicated for people with previously untreated BRAF V600E -mutant mCRC. 7,8 About BRAFTOVI ® (encorafenib) BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAF V600E. Inappropriate 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 commercialize the product in all other countries, including Europe and Asia (excluding Japan and South Korea). INDICATION AND USAGE BRAFTOVI ® (encorafenib) is indicated, in combination with cetuximab and mFOLFOX6, for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test. 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 V600E 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. View the full Prescribing Information . About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com . In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . References SOURCE: Pfizer