NEW YORK – Day One Biopharmaceuticals on Wednesday said it completed submission of a rolling new drug application to the US Food and Drug Administration for tovorafenib as a treatment for progressive pediatric low-grade gliomas (pLGG) harboring BRAF alterations. The submission included updated safety and efficacy data from the FIREFLY-1 trial.
In the Phase II FIREFLY-1 trial, patients with pLGG whose tumors have a known BRAF alteration, including BRAF V600 mutations and KIAA1549:BRAF fusions, received tovorafenib, an oral pan-RAF inhibitor, once a week for 24 months.
In May, Brisbane, California-based Day One initiated a rolling submission to the FDA with results from FIREFLY-1 that had a data cutoff of Dec. 22, 2022. The latest submission includes an updated clinical study report with an additional six months of safety and efficacy data through June 5, 2023. In the new filing, patients had a 67 percent overall response rate; a 93 percent clinical benefit rate including complete responses, partial responses, and stable disease; and a median duration of response of 16.6 months according to Response Assessment for Neuro-Oncology High-Grade Glioma criteria.
Tovorafenib was well tolerated and the majority of adverse events were grade 1 or 2.
Pediatric low-grade gliomas account for 30 percent to 50 percent of all central nervous system tumors diagnosed in children, and BRAF wild-type fusions are the most common cancer-driver mutations found in those patients. There are no approved therapies for most patients with pLGG. Children who do not enter remission after surgery often undergo many years of systemic cancer therapy.
Day One expects the FDA to file the rolling submission by November 2023.