Braftovi Plus Mektovi Demonstrates Sustained Efficacy in Patients with BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer

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Long-term follow-up data from the Phase II PHAROS trial found that Pfizer’s Braftovi (encorafenib) in combination with Mektovi (binimetinib) produced sustained efficacy in patients with BRAF V600E-mutant metastatic non-small cell lung cancer (NSCLC). The findings, which were presented at the ESMO Congress 2024, position the combination as a promising first-line therapy for this type of cancer, according to the trial investigators.¹

“BRAF V600E-mutant metastatic non-small cell lung cancer tends to be aggressive, and effective targeted first-line treatment options with manageable safety profiles are critical for the thousands of people who are diagnosed globally each year,” said PHAROS investigator Gregory Riely, MD, PhD, vice chair, clinical research, Department of Medicine, Memorial Sloan Kettering Cancer Center, in a press release. “The longer-term follow-up results from the PHAROS trial represent an important step forward in the treatment of BRAF V600E-mutant metastatic NSCLC, especially for treatment-naïve patients. These compelling results support the Braftovi plus Mektovi combination as a standard of care option for these patients.”

The open-label, multicenter, single arm PHAROS study examined Braftovi plus Mektovi combination therapy in treatment-naïve and previously treated patients with BRAF V600E-mutant metastatic NSCLC. The primary endpoint of the study was a notable objective response rate (ORR), while the secondary endpoint was duration of response (DoR).

Results demonstrated an ORR of 75% in treatment-naïve patients. Additionally, the median DoR was 40 months and median progression-free survival (PFS) reached 30.2 months. In previously treated patients, ORR was 46%, with a DoR of 16.7 months and PFS of 9.3 months.

The safety profile of Braftovi plus Mektovi was consistent with previous findings and no new safety signals were identified. Treatment-related adverse events (TRAEs) resulted in dose reductions for 26% of patients and treatment discontinuation for 16% of patients. Common TRAEs included nausea, diarrhea, and fatigue. Pfizer warns that new primary malignancies, cutaneous and non-cutaneous, can occur during treatment with this combination. Further, uveitis, hemorrhages, hepatotoxicity, cardiomyopathy, and embryo-fetal toxicity have occurred in patients treated with Braftovi plus Mektovi.

Previously, Braftovi plus Mektovi was approved by the FDA in October 2023, and by the European Commission in August 2024, for the treatment of BRAF V600E-mutant metastatic NSCLC. According to Pfizer, it maintains exclusive rights to the treatment in the United States, Canada, and all countries in Latin America, Africa, and the Middle East. Ono Pharmaceutical hold commercialization and for 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 the Asia-Pacific region.¹

“These potentially practice-changing results from the PHAROS trial show that the combination of Braftovi plus Mektovi is providing long-term compelling efficacy for patients, and although no definitive conclusions can be made across trials, the duration of response and progression-free survival in treatment naïve patients appear to be the longest observed for BRAF V600E–mutant metastatic NSCLC compared with historical outcomes,” said Roger Dansey, MD, chief development officer, oncology, Pfizer, in the press release. “These latest data reflect our deep understanding of the science behind biomarker-driven cancers and add to our legacy in developing innovative targeted treatments in NSCLC. We are continuing to build upon this strong foundation with a pipeline of targeted medicines and combinations across our tumor areas of focus, including the ongoing investigation of Braftovi in earlier settings of metastatic colorectal cancer, and the exploration of a next-generation brain-penetrant BRAF inhibitor.”

Reference

1. Pfizer’s BRAFTOVI® + MEKTOVI® Shows Long-Term Clinically Meaningful Response in Patients with BRAF V600E-Mutant Metastatic Non-Small Cell Lung Cancer. Pfizer. September 14, 2024. Accessed September 17, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-braftovir-mektovir-shows-long-term-clinically