Novartis announced the US Food and Drug Administration (FDA) granted accelerated approval for Tafinlar (dabrafenib) + 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 and 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). Tafinlar + Mekinist is the first and only BRAF/MEK inhibitor 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 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 Dr. Vivek Subbiah, M.D., 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 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, 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.
“Tackling cancer is complex, which is why it is so important that we continue to follow the science as we pursue meaningful advances and new approaches to treating cancer,” said Reshema Kemps-Polanco, Head, Novartis Oncology US. “We are grateful to the patients, and to the multitude of individuals and teams working together to make this latest approval possible as we strive to do more for more people living with cancer.”
The safety profile of Tafinlar + Mekinist observed in these studies was consistent with the known safety profile in other approved indications.
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.