On October 11, 2023, the Food and Drug Administration (FDA) granted approval for the use of encorafenib (Braftovi, developed by Array BioPharma Inc., a subsidiary of Pfizer) in combination with binimetinib (Mektovi, also by Array BioPharma Inc.) for adult patients dealing with metastatic non-small cell lung cancer (NSCLC) characterized by a BRAF V600E mutation, as confirmed by an FDA-endorsed diagnostic test.
In conjunction with this approval, the FDA also sanctioned the utilization of FoundationOne CDx (tissue) and FoundationOne Liquid CDx (plasma) as companion diagnostics for encorafenib with binimetinib. It was emphasized that in cases where no mutation is detected in a plasma sample, a test should be conducted on tumor tissue.
The assessment of efficacy encompassed 98 patients grappling with metastatic NSCLC and possessing the BRAF V600E mutation. These patients were enrolled in the PHAROS study (NCT03915951), which was an open-label, multicenter, single-arm study. Notably, patients were not allowed to have had prior exposure to BRAF or MEK inhibitors. Patients received a regimen of encorafenib and binimetinib until either their disease progressed or they experienced unacceptable levels of toxicity.
The primary efficacy outcomes were gauged by the objective response rate (ORR) per RECIST v1.1 and the duration of response (DoR), as evaluated by an independent review committee. Out of 59 patients who were new to treatment, an ORR of 75% was observed (95% CI: 62, 85), with an indeterminate median DoR (NE) (95% CI: 23.1, NE). Among the 39 patients who had previously undergone treatment, an ORR of 46% was noted (95% CI: 30, 63) along with a median DoR of 16.7 months (95% CI: 7.4, NE).
The adverse reactions most frequently reported (≥25%) were fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash, and cough.
In terms of recommended doses for NSCLC patients positive for the BRAF V600E mutation, the guidance stipulates an oral administration of encorafenib at 450 mg once daily and binimetinib at 45 mg orally twice daily.
This comprehensive review of the application incorporated the Assessment Aid, a voluntary submission from the applicant intended to streamline the FDA's evaluation. Additionally, the application was granted orphan drug designation, underlining the significance and unique status of this therapeutic approach.
