On October 11, 2023, the U.S. Food and Drug Administration (FDA) approved encorafenib (Braftovi®) with binimetinib (Mektovi®) for adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E variant, as detected by an FDA-approved test.
FDA also approved the FoundationOne Liquid CDx (plasma) and FoundationOne CDx (tissue) tests as companion diagnostics for encorafenib with binimetinib. If the plasma testing does not identify a variant, test the tumor tissue as well.
Efficacy was evaluated in 98 patients with metastatic NSCLC with a BRAF V600E variant enrolled in PHAROS (NCT03915951), an open-label, multicenter, single-arm study. Patients were excluded if they had received prior BRAF or MEK inhibitors. Eligible patients received encorafenib and binimetinib until they experienced disease progression or unacceptable toxicity.
The major efficacy outcome measures were objective response rate (ORR), per RECIST v1.1, and duration of response (DoR), as assessed by an independent review committee. Among 59 treatment-naïve patients, ORR was 75% (95% CI = 62, 85) and median DoR was not estimable (NE) (95% CI = 23.1, NE). Among 39 previously treated patients, ORR was 46% (95% CI = 30, 63) and median DoR was 16.7 months (95% CI = 7.4, NE).
The most common adverse reactions reported in at least 25% of patients during clinical trials were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.
The recommended doses for BRAF V600E variant–positive NSCLC are encorafenib 450 mg orally once daily and binimetinib 45 mg orally twice daily.
This review used the Assessment Aid to facilitate FDA’s assessment. The application was granted orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088.
For assistance with single-patient applications for investigational oncology products, healthcare professionals may contact the Office of Oncology Excellence’s Project Facilitate at 240-402-0004 or OncProjectFacilitate@fda.hhs.gov.