FDA to Review Drug Duo for BRAF-Mutant Lung Cancer

The FDA will review Braftovi plus Mektovi for certain patients with lung cancer.

The Food and Drug Administration (FDA) agreed to review a Supplemental New Drug Application of Braftovi (encorafenib) plus Mektovi (binimetinib) for the treatment of patients with BRAF V600E-mutant metastatic non-small cell lung cancer, Pfizer, the pharmaceutical company manufacturing the drugs, announced in a press release.

According to the FDA, a Supplemental New Drug Application is filed by a company asking for their therapy to be reviewed in a different indication than it is already approved for. In this instance, Braftovi plus Mektovi was previously approved to treat patients with BRAF-mutant melanoma.

Now the FDA will review data from the PHAROS trial to determine if the two-drug combination should be approved for the subset of patients with lung cancer. The agency plans on making their decision sometime between October and December 2023.

“Since their initial regulatory approvals, Braftovi and Mektovi have helped improve outcomes in their respective indications of BRAF-mutated metastatic melanoma and BRAF-mutated metastatic colorectal cancer," Dr. Chris Boshoff, chief development officer of oncology and rare disease for Pfizer Global Product Development, said in the press release.

The Phase 2 PHAROS Trial

PHAROS is a multicenter trial involving 98 patients with BRAF V600E-mutant metastatic non-small cell lung cancer. To be eligible for enrollment, patients must have received no prior treatment for their disease or have had one of the following previous therapies:

• First-line standard platinum-based chemotherapy
• First-line treatment with a PD-1 or PD-L1 inhibitor given alone or in combination with platinum-based chemotherapy

Patients on the study must also have a confirmed stage 4, BRAF V600E-mutant non-small cell lung cancer diagnosis, have little or no limitations to their daily activities, and have adequate bone marrow, liver and kidney functioning, according to the clinicaltrials.gov listing of the study.

All patients on the trial received Braftovi and Mektovi; there was no control group.

While the trial is still ongoing and planned to end in June of 2024, it already met its main goal of 24-month objective response rate, which the National Cancer Institute defines as, “the percentage of people in a study or treatment group who have a partial response or complete response to treatment within a certain period of time.”

The study will also look at duration of response, disease control rate, progression-free survival (time patients live during and after treatment without their disease spreading or getting worse), overall survival (time from treatment until death of any cause), incidence and severity of side effects and time to tumor response. Updated findings will be presented at an upcoming medical meeting, according to Pfizer.

Braftovi and Mektovi for This Lung Cancer Subset

Braftovi and Mektovi are both oral drugs, meaning that they are pills that can be taken at home. Braftovi inhibits the BRAF kinase, while Mektovi is a MEK inhibitor, which is involved in the MAPK signaling pathway. Imperfect activation of this pathway has previously been seen in many cancers, such as melanoma, colorectal cancer and non-small cell lung cancer.

BRAF V600E mutations occur in approximately 2% of all non-small cell lung cancer diagnoses. In these instances, tumor growth is fueled by alternations in the MAPK signaling pathway, making the Braftovi/Mektovi combination a promising therapy for this patient population.

"Through our comprehensive development program, the Braftovi and Mektovi combination has shown the potential to help more patients, such as those living with BRAF V600E-mutant non-small cell lung cancer,” Boshoff said.

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