FDA Approval Summary: Tovorafenib for Relapsed or Refractory BRAF-Altered Pediatric Low-Grade Glioma.

On April 23, 2024, the FDA granted accelerated approval to tovorafenib, a type II RAF kinase inhibitor, for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement or BRAF V600 mutation. Efficacy was evaluated in FIREFLY-1 (NCT04775485), a single-arm, open-label, multicenter trial that enrolled patients 6 months to 25 years of age with relapsed or refractory pLGG with an activating BRAF alteration who had received prior systemic therapy. The major efficacy outcome measure was the radiologic overall response rate, defined as the proportion of patients with complete response, partial response, or minor response as determined by blinded independent central review using Response Assessment in Pediatric Neuro-Oncology criteria. A key secondary endpoint was duration of response. In an efficacy population of 76 patients, the overall response rate was 51% (95% confidence interval, 40-63), and the median duration of response was 13.8 months (95% confidence interval, 11.3-not estimable). The required postmarketing clinical trial (FIREFLY-2) was well underway at the time of accelerated approval. This represents the first FDA approval of a systemic therapy for the treatment of patients with pLGG with BRAF fusions or rearrangements.