FDA Approves Braftovi and Mektovi for Some Patients with Metastatic NSCLC

The Food and Drug Administration (FDA) has approved Braftovi (encorafenib) with Mektovi (binimetinib) for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation, the agency announced on Wednesday evening.

The FDA has also approved FoundationOne CDx and FoundationOne Liquid CDx as companion tissue and plasma diagnostics, respectively, for Braftovi with Mektovi, and advised in a news release that if no mutation is detected via a plasma specimen then the patient’s tumor should be tested.

Pfizer, the pharmaceutical company manufacturing the BRAF inhibitor Braftovi and the MEK inhibitor Mektovi, announced in April that the FDA had agreed to review a Supplemental New Drug Application for the combination for the treatment of this population of patients with NSCLC.

The combination had been previously approved in 2018 for the treatment of adult patients with BRAF-mutant unresectable or metastatic melanoma and, when paired with the EGFR inhibitor Erbitux (cetuximab), for the treatment of patients with BRAF V600E-mutant metastatic colorectal cancer (mCRC) after one to two prior lines of treatment in a metastatic setting.

Wednesday’s approval announcement follows the 98-patient, phase 2 PHAROS trial, which launched in 2019, according to clinicaltrials.gov. Results of PHAROS, published in July in the Journal of Clinical Oncology, determined that “for patients with treatment-naïve and previously treated BRAF V600E-mutant metastatic NSCLC, (Braftovi) plus (Mektovi) showed a meaningful clinical benefit with a safety profile consistent with that observed in the approved indication in melanoma.”

Braftovi, as explained by Pfizer, “is an oral small molecule BRAF kinase inhibitor and Mektovi is an oral small molecule MEK inhibitor which target key proteins in the MAPK signaling pathway (RAS-RAF-MEK-ERK). Inappropriate activation of this pathway has been shown to occur in many cancers, including melanoma, (colorectal cancer) and NSCLC.”

Among PHAROS participants, the objective response rate (ORR, patients whose disease responded partially or completely to treatment) was 75% for previously untreated patients and 46% for patients who had received previous lines of treatment, while the median duration of response was not estimable and 16.7 months, respectively, and the median progression-free survival (the time following treatment that a patient lives without a disease worsening) was not evaluable and 9.3 months, respectively, according to the study.

The most common side effects observed in at least 25% of patients included fatigue, nausea, diarrhea, musculoskeletal pain, vomiting, abdominal pain, visual impairment, constipation, dyspnea, rash and cough, the FDA reported.

The agency recommended that patients with BRAF V600E mutation-positive NSCLC be dosed with 450 milligrams of Braftovi daily and 45 milligrams of Mektovi twice daily.

“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, oncology and rare disease, Pfizer Global Product Development, stated in a press release in April. "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.”

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