The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial

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

Katalyst Pilot Study: Using Interactive Activities in Anatomy and Physiology to Teach Children the Scientific Foundation of Healthy Lifestyles

This pilot study evaluated the impact of the Katalyst curriculum, a fifth-grade experiential learning program, on students’ knowledge of a healthy lifestyle’s impact on body functions. Katalyst’s interactive curriculum spans two days and includes four, 60-min stations on body systems: cardiovascular/endocrine, gastrointestinal, neurological, and respiratory/musculoskeletal. Three schools were recruited, and two schools completed the intervention sessions. Prior to beginning the stations, fifth-grade students completed a 37-item questionnaire to assess knowledge and perceptions. Students completed the same survey at the end of the Katalyst intervention. Teachers at the school also completed a survey post intervention to provide feedback on the program. Frequency and paired analyses were conducted on student responses and summative content analysis on teacher and volunteer feedback. The School 1 completer (n = 63) baseline mean knowledge score was 66.2%. The School 2 completer (n = 47) baseline mean knowledge score was 67.3%. Following the Katalyst intervention, both schools showed a statistically significant increase in the mean post score to 70.3% (p = 0.0017) and 78.4%(p < 0.0001) at School 1 (n = 63) and School 2 (n = 47), respectively. Teacher feedback (n = 7) revealed that Katalyst was effective in meeting state educational health standards and teachers perceived that the students benefitted from the program more than “reading about the body systems in a textbook or health magazine„. The Katalyst pilot study appeared to improve fifth-grade students’ knowledge of body systems and health. Katalyst aligned with state educational standards and is supported by teachers for an experiential learning opportunity. The Katalyst curriculum could be a potential avenue for health educators in Appalachia