The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial.
Клиническое исследование II фазыСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Kilburn Lindsay B, Khuong-Quang Dong-Anh, Hansford Jordan R, Landi Daniel, van der Lugt Jasper, Leary Sarah E S, Driever Pablo Hernáiz, Bailey Simon, Perreault Sébastien, McCowage Geoffrey, Waanders Angela J, Ziegler David S, Witt Olaf, Baxter Patricia A, Kang Hyoung Jin, Hassall Timothy E, Han Jung Woo, Hargrave Darren, Franson Andrea T, Yalon Oren Michal, Toledano Helen, Larouche Valérie, Kline Cassie, Abdelbaki Mohamed S, Jabado Nada, Gottardo Nicholas G, Gerber Nicolas U, Whipple Nicholas S, Segal Devorah, Chi Susan N, Oren Liat, Tan Enrica E K, Mueller Sabine, Cornelio Izzy, McLeod Lisa, Zhao Xin, Walter Ashley, Da Costa Daniel, Manley Peter, Blackman Samuel C, Packer Roger J, Nysom Karsten
Аннотация
BRAF genomic alterations are the most common oncogenic drivers in pediatric low-grade glioma (pLGG). Arm 1 (n = 77) of the ongoing phase 2 FIREFLY-1 (PNOC026) trial investigated the efficacy of the oral, selective, central nervous system-penetrant, type II RAF inhibitor tovorafenib (420 mg m-2 once weekly; 600 mg maximum) in patients with BRAF-altered, relapsed/refractory pLGG. Arm 2 (n = 60) is an extension cohort, which provided treatment access for patients with RAF-altered pLGG after arm 1 closure. Based on independent review, according to Response Assessment in Neuro-Oncology High-Grade Glioma (RANO-HGG) criteria, the overall response rate (ORR) of 67% met the arm 1 prespecified primary endpoint; median duration of response (DOR) was 16.6 months; and median time to response (TTR) was 3.0 months (secondary endpoints). Other select arm 1 secondary endpoints included ORR, DOR and TTR as assessed by Response Assessment in Pediatric Neuro-Oncology Low-Grade Glioma (RAPNO) criteria and safety (assessed in all treated patients and the primary endpoint for arm 2, n = 137). The ORR according to RAPNO criteria (including minor responses) was 51%; median DOR was 13.8 months; and median TTR was 5.3 months. The most common treatment-related adverse events (TRAEs) were hair color changes (76%), elevated creatine phosphokinase (56%) and anemia (49%). Grade ≥3 TRAEs occurred in 42% of patients. Nine (7%) patients had TRAEs leading to discontinuation of tovorafenib. These data indicate that tovorafenib could be an effective therapy for BRAF-altered, relapsed/refractory pLGG. ClinicalTrials.gov registration: NCT04775485 .