FDA Approves Pfizer’s Braftovi Plus Cetuximab for Colorectal Cancer with BRAF Mutations

The U.S. Food and Drug Administration (FDA) approved Pfizer’s Braftovi (encorafenib) in combination with cetuximab (Erbitux) for adults with metastatic colorectal cancer (CRC) with a BRAF^V600E mutation. The mutation is identified with an FDA-approved companion diagnostic, and the indication is for after previous therapy.

The FDA’s approval was based on data from the BEACON CRC trial, a Phase III trial specifically focused on CRC patients with the BRAF^V600E mutation. BRAF mutations occur in up to about 15% of metastatic CRC and generally represent a poor prognosis. It was under Priority Review and Breakthrough Therapy designation.

Braftovi is an oral small molecule kinase inhibitor targeting BRAF^V600E. Pfizer has exclusive rights to the drug in the U.S. and Canada. Ono Pharmaceutical Co. has exclusive rights to commercialize it in Japan and South Korea. Medison has rights to commercial the drug in Israel and Pierre Fabre has rights to commercialize it in other countries, including Europe, Latin America and Asia, excluding Japan and South Korea.

Pfizer acquired Braftovi as part of its $11.4 billion acquisition of Array BioPharma in 2019. The drug is also approved with Array’s Mektovi (binimetinib) for unresectable or metastatic melanoma with a BRAF^V600E mutation or V600K mutation. However, CRC is believed to be a bigger opportunity.

“We are pleased by the FDA’s approval of Braftovi in combination with cetuximab, as we are committed to developing targeted medicines that can help people living with certain mutation-driven cancers,” said Chris Boshoff, chief development officer, Oncology, Pfizer Global Product Development. “We are grateful to the patients and study investigators who participated in the Phase III BEACON CRC trial and are proud to now be able to offer a targeted treatment option for people with BRAF^V600E-mutant metastatic CRC who have received prior therapy. Look ahead, we’re committed to continuing to investigate this treatment regimen across earlier lines of therapy.”

Pfizer has built a strong portfolio of targeted cancer drugs approved since 2018. They include Lorbrena (lorlatinib) in second-line ALK-positive non-small cell lung cancer (NSCLC), SMO inhibitor Daurismo (glasdegib) in acute myeloid leukemia (AML), Talzenna (talazoparib) for advanced breast cancer, and Vizimpro (dacomitinib) in lung cancer.

In the BEACON CRC trial, Braftovi and cetuximab demonstrated a median overall survival (OS) of 8.4 months compared to 5.4 months for the control (irinotecan with cetuximab or FOLFIRI with cetuximab). The combination also showed an improved objective response rate (ORR) of 20% compared to 2% for the control and median progression-free survival (mPFS) of 4.2 months with Braftovi plus cetuximab compared to 1.5 months for control.

Colorectal cancer is the third most common form in men globally, and second most common in women. There were about 1.8 million new diagnoses in 2018. In the U.S., about 147,950 people will be diagnosed with cancer of the colon or rectum this year, and about 53,000 are projected to die from it each year. Patients with a BRAF^V600E are two times higher risk of dying than those with the wild-type BRAF.

“As the first-and-only targeted regimen for people with a BRAF^V600E-mutant metastatic CRC who have received prior therapy, Braftovi in combination with cetuximab is a much-needed new treatment option for these patients,” said Scott Kopetz, associate professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center.