On June 23, the U.S. Food and Drug Administration (FDA) granted accelerated approval for dabrafenib (Tafinlar) plus trametinib (Mekinist) for the treatment of adult and pediatric patients aged 6 years and older with unresectable or metastatic solid tumors with a BRAF V600E mutation whose disease has progressed following prior treatment and who have no satisfactory alternative treatment options. In accordance with the Accelerated Approval Program, continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
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.
Dabrafenib/trametinib is the first and only BRAF/MEK inhibitor combination to be approved with a tumor-agnostic indication for solid tumors carrying the BRAF V600E mutation, which drives tumor growth in more than 20 different tumor types, and it is the only BRAF/MEK inhibitor combination approved for use in pediatric patients.
“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,” said 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 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.”
Trials That Supported Approval
The FDA approval was based on clinical efficacy and safety demonstrated in three clinical trials. In the phase II ROAR (Rare Oncology Agnostic Research) basket study and the NCI-MATCH Subprotocol H study, dabrafenib plus trametinib resulted in overall response rates of up to 80% in patients with BRAF V600E–mutated solid tumors, including high- and low-grade glioma, biliary tract cancer, and certain gynecologic and gastrointestinal cancers. An additional study (Study X2101) demonstrated the clinical benefit and acceptable safety profile of dabrafenib plus trametinib in pediatric patients.
The safety profile of dabrafenib plus trametinib observed in these studies was consistent with the known safety profile in other approved indications.