ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors

Inclusion Criteria: * ARM A: Children and young adults with DMG, H3K27 altered (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who completed at least one line of prior therapy. Prior treatment must have included focal radiation therapy and patients must be within 4-14 weeks from completion of radiation therapy to registration (patients must start treatment within 1 week from registration), have not started any other therapies post-radiation, and have no evidence of disease progression. * ARM A: Tumor tissue confirmation of DMG, H3K27 altered is mandatory and pathology must be consistent with a DMG, H3K27 altered. * ARM A: Participants must have recovered from all acute side effects of prior therapy. * ARM A: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team) * ARM B: Newly diagnosed children and young adults (Dose escalation: 2-21 years of age; Dose expansion: 2 years of …