PNOC022 is an open-label, Phase II, adaptive platform study evaluating combination therapy for children and young adults with DMG, including DIPG, at initial diagnosis, after radiation therapy, or at progression. The trial investigates ONC201-based combination therapy, with different cohorts depending on disease stage, molecular/pathology status, prior radiation, and eligibility for other ONC201 trials. The study assesses safety, tolerability, radiographic response, progression-free survival, overall survival, and exploratory biological/imaging endpoints.