Encorafenib With Binimetinib Approved for BRAF V600E–Mutated Non–Small Cell Lung Cancer

Tumor cell staining in non–small cell lung cancer.

The FDA has approved encorafenib (Braftovi®, Array BioPharma Inc.) with binimetinib (Mektovi®, Array BioPharma Inc.) for adult patients with metastatic non–small cell lung cancer (NSCLC) with a BRAF V600E mutation, as detected by an FDA-approved test.  

Why it matters: “Encorafenib is an oral, selective, reversible small-molecule RAF kinase inhibitor, with a long dissociation half-life of >30 hours,” wrote Dr. Gregory J. Riely, MD, PhD, the Vice Chair of the Clinical Trials Office in the Department of Medicine at Memorial Sloan Kettering Cancer Center, and colleagues, in their published results of the PHAROS trial (NCT03915951), on which approval was based. “Binimetinib is an oral, ATP-uncompetitive, reversible inhibitor of MEK1 and MEK2 activation. In patients with BRAF V600E/K-mutant metastatic melanoma, encorafenib in combination with binimetinib demonstrated clinical benefit with an acceptable safety profile.”

What they studied: Safety and efficacy were evaluated in the phase 2, single-arm, open-label, non-randomized trial in which 98 patients were enrolled to receive 450 mg of encorafenib once daily with 45 mg of binimetinib twice daily, both administered orally in 28-day cycles. Patients previously treated with a BRAF or MEK inhibitor were not included. The primary end points measured were objective response rate per RECIST v1.1 and duration of response.

What they found: Among the 98 patients enrolled, 59 were treatment-naïve and 39 were previously treated. Among those who were treatment-naïve, the objective response rate was 75% and the median duration of response was not estimable. Among those who were previously treated, the objective response rate was 46% and the median duration of response was 16.7 months.

Adverse events: The most common adverse events experienced by ≥25% of patients were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.

Conclusion: “Results of the PHAROS study show that encorafenib plus binimetinib had antitumor activity and an acceptable safety profile consistent with that seen in the approved indication in melanoma,” concluded Dr. Riely and colleagues. “Encorafenib plus binimetinib represents a potential new treatment option for patients with BRAF V600E–mutant metastatic NSCLC.”

Instructions: The recommended dosage for patients with BRAF V600E–mutated NSCLC is 450 mg of encorafenib once daily with 45 mg binimetinib twice daily, administered orally.

For More Information

Riely GJ, Smit EF, Ahn MJ, et al (2023). Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600-mutant metastatic non-small-cell lung cancer. J Clin Oncol; 41(21):3700-3711. DOI:10.1200/JCO.23.00774

Clinicaltrials.gov (2023). An open-label study of encorafenib + binimetinib in patients with BRAFV600-mutant non-small cell lung cancer. NLM identifier: NCT03915951.

Braftovi® (encorafenib) and Mektovi® (binimetinib) prescribing information (2023). Array BioPharma Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/210496s014lbl.pdf

US Food and Drug Administration (2023). FDA approves encorafenib with binimetinib for metastatic non-small cell lung cancer with a BRAF V600E mutation. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-encorafenib-binimetinib-metastatic-non-small-cell-lung-cancer-braf-v600e-mutation

Image credit: Roche Diagnostics. Licensed under CC BY-SA 4.0

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