Activity of Tovorafenib in Recurrent or Progressive Pediatric Low-Grade Glioma May Support Future Approval


Based on topline results from tovorafenib in the FIREFLY-1 study, the developer plans to file a new drug application with the FDA.

Tovorafenib monotherapy achieved a 64% objective response rate (ORR) in patients with recurrent or progressive pediatric low-grade glioma, according to topline results from the FIREFLY-1 study (NCT04775485).1

Seventy-seven patients were treated in the study, and 69 patients were evaluable for response in the phase 2, open-label, multicenter study. Fifty-nine of the patients had a BRAF fusion alteration, and no FDA-approved therapies are available for these patients. Moreover, 10 patients had a BRAF mutation. The population had a median of 3 prior lines of therapy (range, 1-9). Prior to joining the study, 60% of the study population had already received at least 1 prior MAPK inhibitor.1,2

In the study, patients between the ages of 6 months and 25 years received tovorafenib monotherapy once-weekly. The trial is a collaborative effort between the Pacific Pediatric Neuro-Oncology Consortium and DayOne Biopharmaceuticals. The goal the the trial is to support the potential regulatory approval of tovorafenib for recurrent or progressive pediatric low-grade glioma.1

The median duration of tovorafenib treatment was 8.4 months in the study. The ORR associated with tovorafenib in the response-evaluable population included confirmed complete response in 4% of patients (n = 3), partial responses in 59% (n = 41), and stable disease in 28% (n = 19). The clinical benefit rate was 91%.

“The responses we’ve observed in the FIREFLY-1 study with weekly monotherapy tovorafenib in children with recurrent or progressive low-grade gliomas are very encouraging,” said Samuel Blackman, MD, PhD, co-founder and chief medical officer of Day One, in a press release. “As tovorafenib progresses in the clinic, we want to thank the patients, their families, the clinical investigators, and the advocates who have chosen to participate in the FIREFLY-1 clinical trial and support the development of a potential new treatment for children in need of new therapeutic options.”

In terms of safety, results were from 77 patients treated with tovorafenib. The agent appeared to be well tolerated with the most common adverse events (AEs) being change in hair color (75%), increased creatine phosphokinase (64%), anemia (46%), fatigue (42%) and maculopapular rash (42%).

“Based on the efficacy and safety profile of tovorafenib observed to date from the FIREFLY-1 trial population, we plan to submit a new drug application in the first half of this year that will include additional follow up from the full study population,” said Jeremy Bender, PhD, chief executive officer of Day One, in the press release. “We look forward to continuing our discussions with regulatory authorities with the hope of bringing this therapy to children in need of new options as soon as possible.”


1. Day One announces topline data from pivotal phase 2 FIREFLY-1 trial demonstrating meaningful responses with tovorafenib (DAY101) in recurrent or progressive pediatric low-grade glioma. News release. January 8, 2023. Accessed January 10, 2023.

2. A study to evaluate DAY101 in pediatric and young adult patients with relapsed or progressive low-grade glioma and advance solid tumors (FIREFLY-1). Updated October 3, 2022. Updated October 3, 2023. January 10, 2023.

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