Multinational phase 2 trial of tovorafenib for relapsed or refractory pediatric low-grade glioma

BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Tovorafenib is an oral, selective, central nervous system-penetrant, type II RAF inhibitor. The multinational phase 2 FIREFLY-1 trial evaluated tovorafenib for relapsed or refractory BRAF-altered pLGG. In cohort 1, the ORR according to RANO-HGG criteria was 67%, meeting the prespecified primary endpoint, with median time to response 3.0 months and median duration of response 16.6 months. Grade 3 or higher treatment-related adverse events were reported for 42% of patients; TRAEs leading to discontinuation of tovorafenib were reported for 7%. The authors conclude that these data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed or refractory pLGG.