FDA Grants Accelerated Approval to Dabrafenib Plus Trametinib for BRAF V600E+ Tumor-Agnostic Indication


Dabrafenib plus trametinib may now be used to treat patients with BRAF V600E–positive solid tumors who have no suitable alternative treatment options following its approval by the FDA.

The BRAF/MEK inhibitor combination of dabrafenib (Tafinlar) plus trametinib (Mekinist) has been granted accelerated approval by the FDA for the treatment of adult and pediatric patients 6 years and older with unresectable or metastatic solid tumors harboring mutations in BRAF V600E following progression on previous treatment who have no satisfactory alternative treatment options, according to drug developer Novartis.

Continued approval of the combination will be contingent on verification of benefit in a confirmatory trial. This marks the first approval of a BRAF/MEK inhibitor combination in a tumor-agnostic indication.

“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, at The University of Texas MD Anderson Cancer Center in Houston, Texas, said in a news release. “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 decision from the FDA was supported by several clinical trials, including the phase 2 ROAR trial (NCT02034110) and the NCI-MATCH (NCT02465060) Subprotocol H study. Data from both trials in patients with BRAF V600E–positive solid tumors—including gliomas and biliary tract, gynecologic, and gastrointestinal cancers—revealed an overall response rate of up to 80%.

For instance, the combination showed clinically meaningful activity in patients with BRAF V600E–mutant recurrent or refractory high- (n = 45) and low-grade glioma (n = 13) who had previously received frontline therapy and were treated on the ROAR trial, with ORRs of 33% (95% CI, 20%-49%) and 69% (95% CI, 39%-91%), respectively.2 In a cohort of patients with BRAF V600E–positive biliary tract cancer with 1 or more prior lines of therapy treated on the same trial (n = 33), the investigator-assessed ORR was 41% (95% CI, 24%-59%).3

In the NCI-MATCH subprotocol, 29 patients with BRAF V600E mutant gastrointestinal, lung, gynecologic, and central nervous system tumors experienced an ORR of 38% (95% CI, 22.9%-54.9%; P <.001).4

The third trial considered for the approval was Study X2102, which showed clinical benefit coupled with acceptable toxicity in pediatric patients with BRAF V600E mutation­–positive cancers.

Of note, no new safety concerns emerged in any of the 3 trials outside of the known safety profile of either agent.

“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,” Reshema Kemps-Polanco, head of Novartis Oncology US, said in a statement. “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.”


  1. Novartis Tafinlar + Mekinist receives FDA approval for first tumor-agnostic indication for BRAF V600E solid tumors. News release. Novartis. June 22, 2022. Accessed June 23, 2022. https://bit.ly/3QUkPf9
  2. Wen PY, Stein A, van den Bent M, et al. Dabrafenib plus trametinib in patients with BRAFV600E-mutant low-grade and high-grade glioma (ROAR): a multicentre, open-label, single-arm, phase 2, basket trial. Lancet Oncol. 2022;23(1):53-64. doi:10.1016/S1470-2045(21)00578-7
  3. Wainberg ZA, Lassen UN, Elez E, et al. Efficacy and safety of dabrafenib (D) and trametinib (T) in patients (pts) with BRAF V600E–mutated biliary tract cancer (BTC): a cohort of the ROAR basket trial. J Clin Oncol. 2019;37(suppl 4):187. doi:10.1200/JCO.2019.37.4_suppl.187
  4. Salama AKS, Li S, Macrae ER, et al. Dabrafenib and trametinib in patients with tumors with BRAFV600E mutations: results of the NCI-MATCH trial Subprotocol H. J Clin Oncol. 2020;38(33):3895-3904. doi:10.1200/JCO.20.00762
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