Clinical stability after tovorafenib treatment in patients with relapsed/refractory pediatric low-grade glioma: Updated results from the phase 2 FIREFLY-1 trial
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: Background In the phase 2 FIREFLY-1 study, tovorafenib monotherapy achieved clinically meaningful, rapid, durable tumor responses in patients with BRAF-altered relapsed/refractory pediatric low-grade glioma (pLGG), supporting regulatory approval in the United States. This updated analysis provides longer follow-up and is based on a data cutoff of June 6, 2025. Methods Efficacy was assessed in patients with BRAF-altered pLGG (arm 1, n=77). Safety was assessed in a combined population that included an extension cohort (arm 2, n=60). Tovorafenib was administered at 420 mg/m2 (not to exceed 600 mg), once weekly, in 28-day cycles. After 26 cycles of treatment, patients could continue tovorafenib or enter a post-treatment observation period with an option of retreatment at progression. Results Median follow-up of patients in arm 1 was 40.6 months. Per Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO-LGG) criteria, overall response rate was 53%, median duration of response was 19.4 months, and median progression-free survival was 16.6 months. However, median time to next treatment was 42.6 months, tracking more closely with time to clinical progression than radiographic progression. For 39 patients who entered post-treatment observation (median follow-up of 16.0 months), median treatment-free interval was not reached; 31 patients remained off therapy with 30 (77%) treatment free for ≥12 months. No new safety signals were identified. Conclusions This updated analysis, with a median of 40.6 months of follow-up, confirmed the clinically meaningful activity of tovorafenib in the treatment of relapsed/refractory BRAF-altered pLGG and demonstrated prolonged clinical stability following completion of tovorafenib treatment. ClinicalTrials.gov ID: NCT04775485.
Source: Neuro-Oncology Pediatrics
Authors: Cassie Kline, Daniel Landi, Dong-Anh Khuong-Quang, Karsten Nysom, Lindsay B Kilburn, Angela J Waanders, Sébastien Perreault, Sabine Mueller, Geoffrey McCowage, Pablo Hernáiz Driever, Sarah E S Leary, David S Ziegler, Hyoung Jin Kang, Olaf Witt, Patricia A Baxter, Simon Bailey, Susan N Chi, Jung Woo Han, Mohamed S Abdelbaki, Timothy E Hassall, Andrea T Franson, Darren Hargrave, Helen Toledano, Michal Yalon Oren, Nada Jabado, Nicholas G Gottardo, Nicolas U Gerber, Samuele Renzi, Devorah Segal, Enrica E K Tan, Liat Oren, Nicholas S Whipple, Jordan R Hansford, Katherine Pehlivan, Jingyang Zhang, Peter Manley, Lindsey Ott, Elly Barry, Johnathan C Maher, Jasper van der Lugt
Institutions: Children's Hospital of Philadelphia, University of Pennsylvania, Duke University, Royal Children's Hospital, Copenhagen University Hospital, Rigshospitalet, Children's National, Lurie Children's Hospital, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, University of California, San Francisco, University of California San Francisco Medical Center, Sydney Children’s Hospitals Network, Humboldt-Universität zu Berlin, Charité - Universitätsmedizin Berlin, Seattle Children's Hospital, UNSW Sydney, Sydney Children's Hospital, Seoul National University, Seoul National University Children's Hospital, German Cancer Research Center, University Hospital Heidelberg, National Center for Tumor Diseases, Hopp Children's Cancer Center Heidelberg, Deutsches Konsortium für Translationale Krebsforschung, Baylor College of Medicine, Texas Children's Hospital, Great North Children's Hospital, Newcastle University, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Severance Hospital, Yonsei University Health System, Washington University in St. Louis, Children's Health Queensland Hospital and Health Service, University of Michigan, Michigan Medicine, C. S. Mott Children's Hospital, Great Ormond Street Hospital, University College London, Tel Aviv University, Schneider Children's Medical Center, Sheba Medical Center, Montreal Children's Hospital, McGill University Health Centre, The Kids Research Institute Australia, The University of Western Australia, Princess Margaret Hospital for Children, Perth Children's Hospital, University Children's Hospital Zurich, CHU de Québec-Université Laval, NYU Langone Health, KK Women's and Children's Hospital, Rambam Health Care Campus, Primary Children's Hospital, University of Utah, Women's and Children's Hospital, South Australian Health and Medical Research Institute, Adelaide University, The University of Adelaide, Day One Biopharmaceuticals (United States), Princess Máxima Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,670
OpenAlex ID: W7155170777
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