Dabrafenib Plus Trametinib Approved as First Tumor-Agnostic Therapy for BRAF V600E–Mutated Solid Tumors

The combination is the first and only therapy to be approved with a tumor-agnostic indication in both children and adults with solid tumors that have a BRAF V600E mutation, Novartis said late Wednesday.

The FDA Wednesday granted accelerated approval for dabrafenib (Tafinlar) and trametinib (Mekinist) as the first tumor-agnostic indication for BRAF V600E–mutated solid tumors.

The approval for the BRAF/MEK inhibitor is for adults and children aged 6 and older with unresectable or metastatic solid tumors with a BRAF V600E mutation who have advanced cancer following earlier treatment and have no other treatment options. It is the only BRAF/MEK inhibitor approved for children, Novartis said.

BRAF mutations drive tumor growth across more than 20 tumor types, including thyroid, brain, and gynecologic cancers. BRAF V600E is the most common type of BRAF mutation, accounting for up to 90% of BRAF-mutant cancers.

“The combination of dabrafenib and trametinib demonstrated meaningful efficacy in multiple BRAF-positive tumor types, including in some patients with rare cancers who have no other treatment options available,” principal investigator Vivek Subbiah, MD, associate professor of investigational cancer therapeutics and center medical director of the Clinical Center for Targeted Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, Texas, said in a statement. “Physicians should consider a BRAF test as a routine diagnostic step that could enable a new option for treating patients with many solid tumors.”

The FDA approval was based on clinical efficacy and safety demonstrated in 3 clinical trials. In the phase 2 ROAR (Rare Oncology Agnostic Research) basket study and the NCI-MATCH Subprotocol H study, the combination resulted in overall response rates of up to 80% in patients with BRAF V600E solid tumors, including high- and low-grade glioma, biliary tract cancer, and certain gynecological and gastrointestinal cancers.

Results from an additional study (Study X2101) demonstrated the clinical benefit and acceptable safety profile in children.