Clinical Trial Finder

Inclusion Criteria:

1. Patient meets one or more of the criteria below: Arm A

• - Closed to further enrollment.

Arm B

• - Diffuse intrinsic pontine glioma (DIPG), defined as tumors with a pontine epicenter and diffuse involvement of the pons.

H3 K27M status does not have to be known or positive for this arm. Arm C. 1. Patients with primary spinal glioma that is positive for the H3 K27M mutation (performed in a laboratory with Clinical Laboratory Improvement Amendments [CLIA] or equivalent certification). Primary spinal glioma must be documented in radiology reporting. OR. 2. Patients with diffuse glioma that is positive for the H3 K27M mutation (performed in a laboratory with CLIA or equivalent certification) AND radiographic evidence of leptomeningeal disease. Leptomeningeal disease must be documented in radiology reporting. Arm D

• - Closed to further enrollment.

Arm E

• - Patients with H3 K27M-mutant glioma or midline glioma of unknown H3 K27M mutational status who received ONC201 and/or ONC206 from an alternative (non-Chimerix) source prior to 30 November 2023 as evidenced by documentation (such as pharmacy receipts).

Other examples may be confirmed by medical monitor. Detection of H3 K27M mutation should be performed in a CLIA-certified or equivalent laboratory. Arm F

• - Patients with H3 K27M-mutant diffuse glioma or midline glioma with unknown H3 K27M mutational status who have completed frontline radiotherapy at least 6 weeks prior to 30 November 2023.

Detection of H3 K27M mutation should be performed in a CLIA-certified or equivalent laboratory. 2. Disease Status. Arm B: Patient is not required to have radiographic or clinical evidence of progressive disease. Arm C: Patient must have progressive disease as defined by Response Assessment in Neuro-Oncology (RANO) criteria or have documented recurrent glioma on diagnostic biopsy. Arm E: Not Applicable. Arm F: Patient must have progressive disease as defined by RANO criteria or have documented recurrent glioma on diagnostic biopsy. 3. Prior Radiotherapy. Arm B: Patient must be at least 14 days from completion of radiotherapy. Arm C: Patient must be at least 90 days from completion of radiotherapy. Arm E: Not applicable. Arm F: Patient must be at least 90 days from completion of frontline radiotherapy and at least 14 days from reirradiation if applicable. 4. Patient must weigh at least 10kg. 5. Washouts. Arm B, C & F: From the projected start of scheduled study treatment, the following time periods must have elapsed from prior anti-cancer treatments: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 6 weeks from anti-cancer antibodies (except 21 days forbevacizumab), 4 weeks (or 5 half-lives, whichever is shorter) from other anti-tumor therapies, and 1 week from devices used to treat cancer. Arm E: No washouts are required for ONC021 and ONC206. All other anti-cancer agents need to be discontinued prior to enrollment with the exception of bevacizumab. 6. Magnetic resonance imaging (MRI) Arms B, C & F: Magnetic resonance imaging (MRI)of patient's glioma within 28 days prior to start of study drug. Arm E: MRI will be obtained within 8 weeks prior to enrollment. 7. Adequate organ and marrow function as defined below: 1. Absolute neutrophil count≥1,000/mm3 without growth factor use ≤7 days prior to treatment (Cycle 1 Day 1 [C1D1]) 2. Hemoglobin ≥8.0 mg/dL without red blood cell transfusion ≤3 days prior to C1D1. 3. Total serum bilirubin≤ 1.5 X upper limit of normal (ULN) 4. AST (SGOT)/ALT (SGPT)≤2 X ULN; ≤5 X ULN if there is liver involvement secondary to tumore. Serum creatinine ≤1.5 X ULN (OR creatinine clearance ≥60mL/min/1.73m2) 5. Arm E: Patients with organ and marrow function values outside the defined criteria must be approved by medical monitor. 8. For patients post pubertal: Female patients must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. Male patients must be surgically sterile or must agree to use effective contraception while taking ONC201 and for at least 90 days after completion of treatment. The decision of effective contraception will be based on the judgment of the principal investigator. 9. Ability to understand a written informed consent document, and the willingness to sign it. Assent will be obtained when appropriate based on the patient age.

Exclusion Criteria:

1. Qualifies for participation in an ongoing ONC201 or ONC206 clinical trial. 2. Arms B, C & F: Previously or current enrollment in an ONC201 clinical trial (including open-label and blinded studies) or expanded access protocol or previous exposure to ONC201 from any source. Arm E: Previous or current enrollment in an ONC201 clinical study (including open-label and blinded studies) or expanded access protocol for the treatment of CNS tumor. 3. Arms B, C, E and F: Current or planned participation in a study of an investigational agent (including ONC206) or using an investigational device. 4. Any known systemic infection that, in the opinion of the investigator, could compromise the safety of the patient, while taking ONC201. 5. Prolongation of QT/QTcF interval (QTc interval >480 milliseconds) using Fridericia's QT correction formula on two ECGs separated by at least 2 days. 6. A history of Torsades de Pointes or heart failure, hypokalemia, or family history of prolonged QT Syndrome. 7. Concomitant use of medication(s) known to prolong the QT/QTc interval.