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Lookup NU author(s): Professor Simon BaileyORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.Background. Due to their anatomical locations, optic pathway gliomas (OPGs) can rarely be cured by resection. Given the importance of preserving visual function, we analyzed radiological and visual acuity (VA) outcomes for the type II RAF inhibitor tovorafenib in the OPG subgroup of the phase 2 FIREFLY-1 trial. Methods. FIREFLY-1 investigated the efficacy (arm 1, n = 77), safety, and tolerability (arms 1/2) of tovorafenib (420 mg/m2 once weekly; 600 mg maximum) in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG). In this post hoc analysis, anti-tumor activity and VA were analyzed in arm 1 patients with OPG. Anti-tumor activity was independently assessed per Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG), Response Assessment in Pediatric Neuro-Oncology-LGG (RAPNO), and RANO-LGG criteria.The data cutoff was June 5, 2023. Results. Forty-two of 77 patients had OPGs; 35 of 42 had ≥2 VA assessments.The overall response rate in the OPG subgroup according to RANO-HGG, RAPNO, and RANO-LGG criteria were 64%, 50%, and 55%, with clinical benefit rates of 95%, 88%, and 90%, respectively. VA per patient was preserved for 80% of patients; 31% demonstrated improved VA; VA per eye was preserved in 87%, with 27% improving.The safety profile in the arm 1 OPG subgroup was similar to the overall FIREFLY-1 safety analysis set. Conclusions. Tovorafenib demonstrated anti-tumor activity in relapsed/refractory BRAF-altered OPG across radiological assessment criteria and was generally well tolerated. Importantly, vision remained stable or improved in most patients.
Author(s): Nysom K, Kilburn LB, Leary SES, Landi DB, de Vos-Kerkhof E, Perreault S, Witt O, Ziegler DS, Driever PH, Franson AT, Baxter PA, Whipple NS, Kline C, Segal D, Jabado N, Bailey S, McCowage G, Hansford JR, Khuong-Quang D-A, Gottardo NG, Hassall T, Han JW, Oren MY, Chi SN, Qiu J, Costa DD, Raju SG, Manley P, Hargrave D
Publication type: Article
Publication status: Published
Journal: Neuro-Oncology
Year: 2025
Volume: 27
Issue: 5
Pages: 1341-1355
Online publication date: 19/12/2024
Acceptance date: 02/04/2018
Date deposited: 10/07/2025
ISSN (print): 1522-8517
ISSN (electronic): 1523-5866
Publisher: Oxford University Press
URL: https://doi.org/10.1093/neuonc/noae274
DOI: 10.1093/neuonc/noae274
Data Access Statement: The FIREFLY-1 trial protocol (confdential information redacted) has previously been published.18 The authors declare that all data supporting the fndings of this subgroup analysis of the FIREFLY-1 trial are available within the article and Supplementary Information. Requests for full datasets will be considered after completion of the trial and analysis of the data, which is anticipated to be December 2026. To request individual participant data associated with any Day One Biopharmaceuticals clinical trial, please email clinical@dayonebio.com. All requests will be evaluated within 8 weeks.
PubMed id: 39700439
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