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The FDA encorafenib (Braftovi) plus binimetinib (Mektovi) for BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC) as determined by an FDA-approved test, the agency announced on Wednesday.

The approval was based on clinical evidence that the combination therapy was active in patients with previously untreated or pretreated BRAF V600E-mutated NSCLC. Coinciding with the approval, the FDA approved the FoundationOne CDx and the FoundationOne Liquid CDx companion diagnostic tests.

About 1% to 2% of NSCLCs are associated with BRAF V600E mutations.

"BRAF V600E mutations identify a unique subtype of metastatic non-small cell lung cancer that presents an actionable biomarker that precision medicines like Braftovi and Mektovi combination therapy can help address," said Gregory Riely, MD, PhD, of Memorial Sloan Kettering Cancer Center in New York City, in a from Pfizer.

Primary support for the encorafenib-binimetinib approval came from the 98-patient phase II , a multicenter, open-label, single-arm evaluation of patients with metastatic BRAF V600E-mutated NSCLC. The primary endpoint was objective response rate (ORR), with study results showing an ORR of 75% in 59 patients with previously untreated disease and an ORR of 46% in 39 previously treated patients.

Duration of response was 12 months or longer for 59% responding patients in the previously untreated subgroup and for 33% of the previously treated patients. Median duration of response was 16.7 months.

"The PHAROS trial demonstrated that these patients could benefit from Braftovi and Mektovi targeted therapy regardless of their prior treatment history," noted Riely, who co-authored the study. "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."

Encorafenib plus binimetinib join dabrafenib (Tafinlar) plus trametinib (Mekinist) as approved targeted therapies for BRAF V600E-mutated NSCLC. Encorafenib plus binimetinib also has FDA approval for advanced melanoma associated with BRAF V600E mutations. Encorafenib is approved for use with cetuximab (Erbitux) in BRAF V600E-mutated colorectal cancer, while dabrafenib plus trametinib has tumor-agnostic approval for solid tumors with BRAF V600E mutations.

In the PHAROS trial, the most common (≥25% of patients) adverse events (AEs), regardless of causality or severity, were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough. Serious AEs occurred in 38% of patients, and included hemorrhage (6%); diarrhea (4.1%); anemia, dyspnea, and pneumonia (3.1% each); and arrhythmia, device-related infection, edema, myocardial infarction, and pleural effusion (2% each).

AEs led to discontinuation of binimetinib in 17% of patients and to discontinuation of encorafenib in 16%.

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