The Food and Drug Administration (FDA) has granted accelerated approval to Tafinlar® (dabrafenib) + Mekinist® (trametinib) for the treatment of individuals 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.
The accelerated approval was based on data from two phase 2 trials: the ROAR basket study (ClinicalTrials.gov Identifier: NCT02034110) and the NCI-MATCH Subprotocol H study (ClinicalTrials.gov Identifier: NCT02465060). Results showed the combination treatment resulted in objective response rates (ORR) 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.
The efficacy of dabrafenib + trametinib was also evaluated in 48 pediatric patients, including 34 patients with low-grade glioma and 2 patients with high-grade glioma (Study X2101; ClinicalTrials.gov Identifier: NCT02124772). Among patients with a BRAF V600E mutation, the ORR was reported to be 25% (95% CI, 12-42). For the 9 patients who responded, the duration of response was at least 6 months for 78% and at least 24 months for 44% of patients.
The safety profile of the combination was consistent with the known safety profile in other approved indications.
Continued approval for this indication, as stipulated in the accelerated approval program, may be contingent on verification of clinical benefit in 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,” said principal investigator Dr 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.”
Novartis Tafinlar + Mekinist receives FDA approval for first tumor-agnostic indication for BRAF V600E solid tumors. News release. Novartis. Accessed June 23, 2023. https://www.prnewswire.com/news-releases/novartis-tafinlar–mekinist-receives-fda-approval-for-first-tumor-agnostic-indication-for-braf-v600e-solid-tumors-301573580.html