FDA Accepts sNDAs for Encorafenib and Binimetinib for BRAF V600-Mutated NSCLC
Results from the phase 2 PHAROS trial of encorafenib plus binimetinib in patients with BRAF V600E-mutant metastatic non–small cell lung cancer has led the FDA to accept supplemental new drug applications for the agents. Further data will be presented at an upcoming medical meeting.
The FDA has accepted for review supplemental new drug applications (sNDAs) for encorafenib (Braftovi) and binimetinib (Mektovi) for patients with metastatic non–small cell lung cancer (NSCLC) that harbors a BRAF V600E mutation, as detected by an FDA-approved test.1
Both sNDAs are supported by data from the phase 2 PHAROS trial (NCT03915951) which assessed 98 patients with BRAF V600E-mutant metastatic NSCLC to determine the safety, tolerability, and efficacy of encorafenib combined with binimetinib and met its primary end point of objective response rate.
The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is set for the end of 2023 for the sNDAs. The combination is currently approved in the United States for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test. Encorafenib in combination with cetuximab is also approved for the treatment of adult patients with metastatic colorectal cancer (CRC) who have a BRAF V600E mutation, as detected by an FDA-approved test, after prior therapy.
“For more than a decade, Pfizer Oncology has been at the forefront of bringing biomarker-driven treatment options to patients with cancer. Since their initial regulatory approvals, [encorafenib and binimetinib] have helped improve outcomes in their respective indications of BRAF-mutated metastatic melanoma and BRAF-mutated metastatic colorectal cancer," said Chris Boshoff, MD, PhD, chief development officer, Oncology and Rare Disease, Pfizer Global Product Development, in the press release. "Through our comprehensive development program, the [encorafenib and binimetinib] combination has shown the potential to help more patients, such as those living with BRAF V600E-mutant non-small cell lung cancer. These sNDAs build on Pfizer’s long heritage of meeting the diverse needs of people with NSCLC, and we look forward to working with the FDA on their review of these applications.”
The open-label, multicenter, non-randomized, phase 2 PHAROS study is assessing the safety, tolerability, and efficacy of encorafenib combined with binimetinib in patients with BRAF V600E-mutant metastatic NSCLC.2
Patients enrolled will receive encorafenib 450 mg once daily with binimetinib 45 mg twice daily following a 28-day cycle. Inclusion in the study is open to patients aged 18 years and older with a histologically confirmed diagnosis of NSCLC that is currently stage IV harboring a BRAF V600E mutation. Patients must either be treatment-naïve or have received first-line platinum-based chemotherapy or first-line treatment with an anti-PD-1/ PD-L1 inhibitor given alone or in combination with platinum-based chemotherapy, have presence of measurable disease, have an ECOG performance status of 0 or 1, and have adequate bone marrow, hepatic, and renal function.
The primary end point being assessed in the trial is objective response rate (ORR), based on independent radiologic review, and secondary end points are duration of response, disease control rate, progression-free survival, ORR, time to response, overall survival, and incidence and severity of adverse events.
The trial is being conducted across 53 sites in the United States, Italy, the Netherlands, South Korea, and Spain, and has an estimated study completion date of June 30, 2024.
Further and more detailed results from the PHAROS study will be presented at an upcoming scientific congress.1
