FDA Accepts sNDAs for Encorafenib and Binimetinib in BRAF V600E–Mutant NSCLC

The FDA has accepted for review supplemental new drug applications (sNDAs) for the combination of encorafenib (Braftovi) and binimetinib (Mektovi) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) harboring a BRAF V600E mutation, as detected by an FDA-approved test.¹

The sNDAs are supported by data from the phase 2 PHAROS trial (NCT03915951), which demonstrated that the combination of encorafenib and binimetinib achieved its primary end point of objective response rate (ORR) in patients with BRAF V600E–mutant metastatic NSCLC. Detailed results from the trial will be presented at an upcoming scientific congress.

The FDA is expected to decide on the applications in the fourth quarter of 2023, per the Prescription Drug User Fee Act.

“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,” Chris Boshoff, MD, PhD, chief development officer, Oncology and Rare Disease, Pfizer Global Product Development, said in a 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 NSCLC. 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.”

In the United States, the combination of encorafenib and binimetinib is approved for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.² Encorafenib is also approved for use in combination with cetuximab (Erbitux) for pretreated patients with metastatic colorectal cancer with a BRAF V600E mutation, as detected by an FDA-approved test.³

The open-label, multicenter, non-randomized, PHAROS trial evaluated the safety, tolerability, and efficacy of encorafenib plus binimetinib in 98 patients with BRAF V600E–mutant metastatic NSCLC.⁴ Two cohorts of patients were enrolled: those who had not received prior systemic therapy for advanced or metastatic disease, and those who had received either first-line platinum-based chemotherapy or first-line PD-1/PD-L1 inhibition alone or in combination with platinum-based chemotherapy.

Additional eligibility criteria stated that patients must have histologically confirmed, stage IV NSCLC with a locally confirmed BRAF V600E mutation in tumor tissue. Patients with BRAF V600K and BRAF V600D mutations were also given consideration. Patients needed to have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, and adequate bone marrow, hepatic, and renal function.

In the trial, patients self-administered 450 mg of encorafenib in 6, 75-mg capsules once daily plus 45 mg of binimetinib in 3, 15-mg tablets twice daily.

The primary end point of the trial was ORR, based on independent radiologic review per RECIST v1.1 criteria. Secondary end points included investigator-assessed ORR, duration of response, disease control rate, progression-free survival, overall survival, safety, and time to tumor response.

The trial was conducted globally across 53 sites in Italy, the Netherlands, South Korea, Spain, and the United States.

References

1. FDA accepts Pfizer’s supplemental new drug applications for Braftovi + Mektovi. News release. Pfizer. April 4, 2023. Accessed April 4, 2023. https://investors.pfizer.com/Investors/News/
2. FDA approves encorafenib and binimetinib in combination for unresectable or metastatic melanoma with BRAF mutations. News release. FDA. June 27, 2018. Accessed April 4, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/
3. FDA expands Lilly's ERBITUX (cetuximab) label with combination of BRAFTOVI (encorafenib) for the treatment of BRAF V600E mutation-positive metastatic colorectal cancer (CRC) after prior therapy. News release. Eli Lilly and Company. September 29, 2021. Accessed April 4, 2023. https://investor.lilly.com/news-releases/news-release-details/
4. An open-label study of encorafenib + binimetinib in patients with BRAFV600-mutant non-small cell lung cancer. ClinicalTrials.gov. Updated March 17, 2023. Accessed April 4, 2023. https://clinicaltrials.gov/ct2/show/NCT03915951