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BRAFTOVI + MEKTOVI continued to show a substantial median overall survival benefit of 47.6 months in treatment-naïve patients with BRAF V600E-mutant metastatic non-small cell lung cancer after approximately four years
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Results from the Phase 2 PHAROS trial potentially establish new benchmark with targeted combination therapies for this patient population
Sunday, October 19, 2025 - NEW YORK--(BUSINESS WIRE)-- Pfizer Inc. (NYSE: PFE) today announced updated follow-up results from the single-arm Phase 2 PHAROS trial evaluating BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) for the treatment of adults with metastatic non-small cell lung cancer (mNSCLC) with a BRAF V600E mutation. In treatment-naïve patients, the median overall survival (OS) was 47.6 months (95% confidence interval [CI], 31.3, not estimable) after a median follow-up of 52.3 months. In previously treated patients, the median OS was 22.7 months (95% CI, 14.1, 32.6), after a median follow-up of 48.2 months. The four-year OS rates were 49% (95% CI, 35, 62) and 31% (95% CI, 16, 47) for treatment-naïve and previously treated patients, respectively. These data, from pre-specified secondary trial endpoints, will be presented today in an oral presentation (1849MO) at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany, and have been simultaneously published in the Journal of Clinical Oncology.
"The PHAROS trial results set a new standard for NSCLC patients with the BRAF V600E mutation, with survival outcomes nearing four years—the longest survival we've seen in people with treatment-naïve metastatic NSCLC who harbor a BRAF V600E mutation," said Melissa Johnson, M.D., Director of Lung Cancer Research at Sarah Cannon Research Institute and PHAROS investigator. "These findings, which highlight the potential impact of encorafenib and binimetinib for newly diagnosed metastatic NSCLC patients with BRAF V600E, offer renewed optimism for their prognosis and treatment goals."
Lung cancer is the number one cause of cancer-related deaths around the world.1 NSCLC accounts for approximately 80-85% of lung cancers,2 with BRAF V600E mutations occurring in about 2% of patients with NSCLC.3 Prior to the development of targeted treatments, patients with BRAF V600E-mutant metastatic NSCLC had poor outcomes with standard chemotherapy.4
At the time of this analysis, the safety profile of BRAFTOVI + MEKTOVI was consistent with previous findings. The most common (≥30%) treatment-related adverse events were nausea (52%), diarrhea (44%), fatigue (33%), and vomiting (30%).
"These long-term survival results reinforce Pfizer's unwavering commitment to improving outcomes in lung cancer," said Jeff Legos, Chief Oncology Officer, Pfizer. "The findings provide hope for treatment-naïve BRAF V600E mNSCLC patients and their families and underscore the importance of advancing therapies that can provide a sustained impact for patients.”
The Phase 2 PHAROS trial (NCT03915951) is an open-label, multicenter, single-arm study examining BRAFTOVI + MEKTOVI combination therapy in treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC. BRAFTOVI + MEKTOVI was approved by the U.S. Food and Drug Administration (FDA) in October 2023, and by the European Commission in August 2024, for the treatment of BRAF V600E-mutant metastatic NSCLC based on the initial objective response rate (ORR; the primary endpoint) and duration of response (secondary endpoint) results from the PHAROS trial. The ORR was 75% (95% CI: 62, 85) for treatment-naïve patients (n=59) and 46% (95% CI: 30, 63) for previously treated patients (n=39).
Pfizer is continuing its commitment to help non-scientists understand the latest findings with the development of abstract plain language summaries (APLS) for company-sponsored research being presented, which are written in non-technical language. Those interested in learning more can visit www.Pfizer.com/apls to access the summaries.
About BRAF V600E-mutant non-small cell lung cancer (NSCLC)
NSCLC treatment has dramatically evolved, enabling more individualized treatment options based on molecular profiles and immunologic status. BRAF mutations exemplify this precision medicine opportunity—while BRAF V600E mutations occur in only about 2% of NSCLC cases,3 they represent approximately half of all BRAF-mutant metastatic NSCLC.5 Targeting BRAF offers potential to inhibit tumor growth and proliferation driven by these specific mutations.6
Despite this evolution, unmet needs remain for advanced disease. Approximately one in six patients with advanced NSCLC have no biomarker testing results prior to first-line treatment.7 Among tested patients, many do not receive targeted therapy or have limited to no options available for targeted therapy.8-10
About BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib)
BRAFTOVI is an oral small molecule kinase inhibitor that targets BRAF V600E, and MEKTOVI is an oral small molecule MEK inhibitor, both of which target key proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of proteins in this pathway has been shown to occur in certain cancers, including melanoma, CRC, and NSCLC.
Pfizer has exclusive rights to BRAFTOVI + MEKTOVI in the U.S., Canada, Latin America, Middle East, and Africa. Ono Pharmaceutical Co., Ltd. has exclusive rights to commercialize both products in Japan and South Korea, Medison has exclusive rights in Israel and Pierre Fabre Laboratories has exclusive rights in all other countries, including Europe and Asia (excluding Japan and South Korea). The PHAROS trial is conducted with support from Pierre Fabre.
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 multispecific 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 include 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.
References
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2American Cancer Society. What is lung cancer? Available at: https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Last accessed: September 2025.
3American Lung Association. BRAF and lung cancer. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/braf. Last accessed: September 2025.
4Planchard D, Sanborn RE, Negrao MV, Vaishnavi A, Smit EF. BRAFV600E-mutant metastatic NSCLC: Disease overview and treatment landscape. NPJ Precis Oncol. 2024;8(1):90.
5Paik PK, Arcila ME, Fara M, et al. Clinical characteristics of patients with lung adenocarcinomas harboring BRAF mutations. J Clin Oncol. 2011;29(15):2046-51.
6Lieu CH, Corcoran RB, Overman MJ. Integrating biomarkers and targeted therapy into colorectal cancer management. Am Soc Clin Oncol Educ Book. 2019;39:207-215.
7Evangelist MC, et al. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 9109.
8Hendriks LE, Kerr KM, Menis J, et al. Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2023 Apr;34(4)339-357.
9Non-Small Cell Lung Cancer, Version 3.2025. NCCN Clinical Practice Guidelines in Oncology. Accessed April 17, 2025.
10Dennis MJ, et al. Presented at: AACR Annual Meeting; April 5-10, 2024; San Diego, CA. Abstract 2552.