Pfizer Inc. (NYSE: PFE) announced that the U.S. Food and Drug Administration (FDA) has approved BRAFTOVI^® (encorafenib) + MEKTOVI^® (binimetinib) for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.¹ BRAF V600E mutations can be assessed from either plasma or tumor tissue using the FoundationOne Liquid CDx or the FoundationOne CDx FDA-approved companion diagnostic tests, respectively.

“Today’s approval builds on our long-standing commitment to deliver innovative, personalized medicines to patients with lung cancer. By pursuing precision medicines that target a patient’s specific type of cancer, we are leveraging our deep understanding of tumor biology to help address the underlying cause of disease,” said Chris Boshoff, M.D., Ph.D., Chief Oncology Research and Development Officer and Executive Vice President at Pfizer. “Since its initial FDA approval in 2018, BRAFTOVI + MEKTOVI combination therapy has helped thousands of people living with BRAF V600E- or V600K-mutant unresectable or metastatic melanoma.²We look forward to helping even more patients with our BRAFTOVI + MEKTOVI targeted combination therapy.”

The FDA’s approval is based on data from the ongoing Phase 2 PHAROS clinical trial (NCT03915951), an open-label, multicenter, single‑arm study examining BRAFTOVI + MEKTOVI combination therapy in both treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC.

“BRAF V600E mutations identify a unique subtype of metastatic non-small cell lung cancer that presents an actionable biomarker that precision medicines like BRAFTOVI + MEKTOVI combination therapy can help address,” said Gregory Riely, M.D., Ph.D., Vice Chair, Clinical Research in the Department of Medicine at Memorial Sloan Kettering Cancer Center (MSK) and PHAROS investigator. “The PHAROS trial demonstrated that these patients could benefit from BRAFTOVI + MEKTOVI targeted therapy regardless of their prior treatment history. Given the specific efficacy and safety profile, patients and providers now have another option to help personalize treatment plans based on individual risk factors and preferences.”

The PHAROS study met its major efficacy outcome measures of objective response rate (ORR), as assessed by independent review committee (IRC), and duration of response (DOR) in both treatment groups. For treatment-naïve patients (n=59), ORR was 75% (95% CI: 62, 85), and 59% of the patients responded for at least 12 months. Median DOR was not estimable (NE) for this group at the time of data cutoff. For previously treated patients (n=39), ORR was 46% (95% CI: 30, 63), and 33% of the patients responded for at least 12 months. Median DOR was 16.7 months (95% CI: 7.4, NE). These data were presented earlier this year at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in the Journal of Clinical Oncology (JCO).³

The most common (≥25%) all-causality adverse reactions observed in the PHAROS trial were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough. A total of 17% of patients experienced an adverse reaction that resulted in permanent discontinuation of MEKTOVI and 16% experienced an adverse event that resulted in permanent discontinuation of BRAFTOVI. Serious adverse reactions occurred in 38% of patients. Serious adverse reactions occurring in ≥2% of patients included hemorrhage (6%), diarrhea (4.1%), anemia, dyspnea, pneumonia (3.1% each), arrhythmia, device-related infection, edema, myocardial infarction, and pleural effusion (2% each). Fatal adverse reactions occurred in 2% of patients, including intracranial hemorrhage and myocardial infarction (1% each).

BRAFTOVI + MEKTOVI is also FDA-approved for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. BRAFTOVI is FDA-approved, in combination with cetuximab, for the treatment of adult patients with metastatic colorectal cancer (CRC) with a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.

Pfizer has exclusive rights to BRAFTOVI and MEKTOVI in the U.S., Canada, and all countries in Latin America, Africa, and the Middle East. 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 has exclusive rights in all other countries, including Europe and Asia-Pacific (excluding Japan and South Korea).

The PHAROS trial is conducted with support from Pierre Fabre.