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Novel Strategies Under Exploration in Pediatric Low-Grade Glioma
Volume 1
Issue 1

Dr Leary on Tovorafenib in Pediatric Low-Grade Glioma

Sarah E. S. Leary, MD, MS, discusses findings from the phase 2 FIREFLY-1 trial in pediatric patients with low-grade glioma.

Sarah E. S. Leary, MD, MS, attending physician, medical director, Pediatric Brain Tumor Program, Seattle Children’s Hospital; professor, Department of Pediatrics, University of Washington School of Medicine; medical director, Clinical Research, Ben Towne Center for Childhood Cancer Research, discusses findings from the phase 2 FIREFLY-1 trial (NCT04775485) in pediatric patients with low-grade glioma.

Dr Leary on the Rationale for Evaluating Tovorafenib in BRAF-Mutant Low-Grade Glioma

The FIREFLY-1 trial is investigating the efficacy and safety of the pan-RAF inhibitor tovorafenib in pediatric and young adult patients aged 6 months to 25 years who have RAF-altered tumors that have progressed on at least 1 prior line of systemic therapy. The registrational arm includes patients with recurrent or progressive low-grade glioma harboring an activating BRAF alteration, as low-grade gliomas are driven by the BRAF pathway. An extension arm includes patients with recurrent or progressive low-grade glioma harboring an activating RAF alteration, and a third arm includes patients with locally advanced or metastatic RAF-altered solid tumors outside the central nervous system.

The ongoing phase 1b PNOC014 trial (NCT03429803) is investigating tovorafenib in pediatric patients with RAF-altered low-grade glioma. Previously reported findings from this trial demonstrated that of 8 pediatric patients with relapsed low-grade glioma harboring RAF fusions who received tovorafenib, 2 achieved a complete response (CR), 3 achieved a partial response (PR), 2 had prolonged stable disease (SD), and 1 had progressive disease (PD).

The preliminary efficacy data from FIREFLY-1 align with the previously reported findings from PNOC014, Leary says.

Dr Leary on Safety and Efficacy Findings From the FIREFLY-1 Trial

Of the 69 evaluable patients in the registrational arm of FIREFLY-1, the overall response rate was 67%, with 6% of patients achieving a CR and 61% of patients achieving a PR. Additionally, 26% and 6% of patients had best responses of SD and PD, respectively.

No new safety signals occurred with tovorafenib in this trial beyond known adverse effects (AEs) associated with RAF inhibitors, Leary notes. Treatment-emergent AEs (TEAEs) of any grade occurred in 100% of patients in the registrational arm, and any-grade treatment-related AEs occurred in 98% of patients. The most common TEAEs of grade 3 or higher were maculopapular rash, fatigue, decreased appetite, and vomiting.

These encouraging findings emphasize the efficacy of tovorafenib in patients with BRAF-mutant low-grade glioma who have progressed on other therapies, Leary concludes.

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