Pfizer Reports Updated Results of PHAROS Trial for BRAFTOVI + MEKTOVI in BRAF V600E Mutant Metastatic NSCLC

Pfizer has announced updated follow-up results from the Phase 2 PHAROS trial evaluating BRAFTOVI + MEKTOVI for metastatic non-small cell lung cancer with a BRAF V600E mutation. The median overall survival was 47.6 months for treatment-naive patients and 22.7 months for previously treated patients. The four-year OS rates were 49% and 31% for treatment-naive and previously treated patients, respectively. These data will be presented at the ESMO Congress and have been published in the Journal of Clinical Oncology.

Pfizer Inc. (NYSE: PFE) has announced updated follow-up results from the Phase 2 PHAROS trial, which evaluated the efficacy of BRAFTOVI® (encorafenib) + MEKTOVI® (binimetinib) for the treatment of metastatic non-small cell lung cancer (mNSCLC) with a BRAF V600E mutation. The results, presented at the 2025 European Society for Medical Oncology (ESMO) Congress in Berlin, Germany, and published in the Journal of Clinical Oncology, show significant median overall survival (OS) benefits for both treatment-naive and previously treated patients.

For treatment-naive patients, the median OS was 47.6 months (95% CI, 31.3, not estimable), with a four-year OS rate of 49% (95% CI, 35, 62). In contrast, previously treated patients had a median OS of 22.7 months (95% CI, 14.1, 32.6), with a four-year OS rate of 31% (95% CI, 16, 47). These findings establish a new benchmark for targeted combination therapies in this patient population, offering renewed optimism for the prognosis of patients with BRAF V600E-mutant metastatic NSCLC.

"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 remains the leading cause of cancer-related deaths worldwide, with NSCLC accounting for approximately 80-85% of lung cancers. BRAF V600E mutations occur in about 2% of NSCLC cases, representing approximately half of all BRAF-mutant metastatic NSCLC, according to a Morningstar article.

The safety profile of BRAFTOVI + MEKTOVI in the PHAROS trial was consistent with previous findings, with the most common (≥30%) treatment-related adverse events being nausea (52%), diarrhea (44%), fatigue (33%), and vomiting (30%), as reported in the Morningstar article.

Jeff Legos, Chief Oncology Officer at Pfizer, emphasized the significance of these long-term survival results: "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 PHAROS trial (NCT03915951) is an open-label, multicenter, single-arm study examining BRAFTOVI + MEKTOVI combination therapy in treatment-naive and previously treated patients with BRAF V600E-mutant metastatic NSCLC. The trial's initial objective response rate (ORR) and duration of response results led to the FDA approval of BRAFTOVI + MEKTOVI in October 2023, and by the European Commission in August 2024, for the treatment of BRAF V600E-mutant metastatic NSCLC, as noted in the Morningstar article.