FDA Approves Drug Combination for Tumor Agnostic Indication

The FDA approved the combination of Tafinlar and Mekinist for solid tumors with a BRAF V600E mutation. This is the first therapy to be approved that is tumor agnostic for patients with this mutation.

The FDA has granted accelerated approval for the combination of Tafinlar (dabrafenib) and Mekinist (trametinib) for the treatment of adult and pediatric patients 6 years of age and older with unresectable or metastatic solid tumors with BRAF V600E mutation who have progressed following prior treatment. Both therapies were developed and marketed by Novartis.

Tafinlar + Mekinist is the first BRAF/MEK inhibitor to be approved with a tumor-agnostic indication for solid tumors carrying the BRAF V600E mutation. It is the only BRAF/MEK inhibitor approved for use in pediatric patients. Continued approval for this indication is on clinical benefit in a confirmatory trials.

“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 Dr. Vivek Subbiah, M.D., said in a press release. He is associate professor of Investigational Cancer Therapeutics and center medical director of the Clinical Center for Targeted Therapy, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center in Houston, Texas. “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 approval was based on clinical efficacy and safety demonstrated in three clinical trials. In the phase 2 ROAR (Rare Oncology Agnostic Research) basket study and the NCI-MATCH Subprotocol H study, Tafinlar + Mekinist 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. An additional study (Study X2101) demonstrated the clinical benefit and acceptable safety profile of Tafinlar + Mekinist in pediatric patients.

BRAF mutations have been identified as drivers of cancer growth across a wide range of solid tumors, including in rare cancer types that can be challenging to study in Phase III trials and often have limited treatment options. BRAF V600E is the most common type of BRAF mutation, accounting for up to 90% of BRAF-mutant cancers.

Both Tafinlar and Mekinst are approved as a single agent to treat metastatic melanoma, non-small cell lung cancer, and metastatic thyroid cancer.