A Study of Ad-RTS-hIL-12 + Veledimex in Pediatric Subjects With Brain Tumors Including DIPG

Inclusion Criteria: 1. Male or female subjects ≤ 21 years-of-age with the demonstrated ability to swallow capsules whole and who are willing to provide access to previously obtained biopsy results 2. Provision of written informed consent and assent, when applicable, for tumor resection, stereotactic surgery, tumor biopsy, sample collection, and/or treatment with study drug prior to undergoing any study-specific procedures 3. Arm 1: Evidence of recurrent or progressive supratentorial tumor, which has shown a \> 25% increase in bi dimensional measurements by MRI or is refractory with significant neuro deterioration that is not otherwise explained with no known curative therapy, not in direct continuity with the ventricular system (e.g., there is physical separation between the tumor and ventricle, the tumor does not open directly into the ventricular system). Arm 2: Clinical presentation of DIPG and compatible MRI with approximately 2/3 of the pons included and without evidence of dissemination. Subjects should be ≥ 2 weeks and ≤ 10 weeks post standard focal radiotherapy (ie, dose of 5400 to 5960 cGy and maximum dexamethasone of 1 mg/m2/day) 4. At the time of registration, subjects must have recovered from the toxic effects of previous treatments, as determined by the treating physician. 1. Targeted agents, including small-molecular tyrosine kinase inhibitors: 2 weeks 2. Other cytotoxic agents: 3 weeks 3. Nitrosoureas: 6 weeks 4. Monoclonal antibody immunotherapies (eg, PD-1, CTLA-4): 6 weeks 5. Vaccine-based and/or viral therapy: 3 months 5. On a stable or decreasing dose of dexamethasone for the previous 7 days 6. Able to undergo standard MRI scans with contrast agent before enrollment and after treatment 7. Have age-appropriate functional performance: 1. Lansky score ≥ 40 or 2. Karnofsky score \> 50 or 3. Eastern Cooperative Oncology Group (ECOG) score ≤ 2 8. Have adequate bone marrow reserves and liver and kidney function, as assessed by the following laboratory requirements: 1. Hemoglobin ≥ 8 g/L 2. Absolute lymphocyte count ≥ 500/mm3 3. Absolute neutrophil count ≥ 1000/mm3 4. Platelets ≥ 100,000/mm3 (untransfused \[\> 5 days\] without growth factors) 5. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) for age 6. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN for age 7. Total bilirubin \< 1.5 x ULN for age 8. International normalized ratio (INR) and activated thromboplastin time within normal institutional limits 9. Male and female subjects of childbearing potential must agree to use a highly reliable method of birth control (expected failure rate \< 1% per year) from the Screening visit through 28 days after the last dose of study drug. Women of childbearing potential must have a negative pregnancy test at screening. Exclusion Criteria: 1. Radiotherapy treatment prior to the first veledimex dose: 1. Focal radiation ≤ 4 weeks 2. Whole-brain radiation ≤ 6 weeks 3. Cranio-spinal radiation ≤ 12 weeks NOTE: Subjects in Arm 2 (ie, with DIPG) must be ≥ 2 weeks and ≤ 10 weeks after standard focal radiotherapy (dose of 5400 to 5960 cGy and maximum dexamethasone of 1 mg/m2/day) 2. Subjects with clinically significant increased intracranial pressure (eg, impending herniation or requirement for immediate palliative treatment) or uncontrolled seizures 3. Subjects whose body surface area (BSA) would expose them to \< 75% or \> 125% of the target dose 4. Known immunosuppressive disease, autoimmune condition, and/or chronic viral infection (eg, human immunodeficiency virus \[HIV\], hepatitis) 5. Use of systemic antibacterial, antifungal, or antiviral medications for the treatment of acute clinically significant infection within 2 weeks of first veledimex dose. Concomitant therapy for chronic infections is not allowed. Subjects must be afebrile prior to Ad-RTS-hIL-12 injection; only prophylactic antibiotic use is allowed perioperatively 6. Use of enzyme-inducing antiepileptic drugs (EIAEDs) within 7 days prior to the first dose of study drug 7. Other concurrent clinically active malignant disease, requiring treatment 8. Nursing or pregnant females 9. Prior exposure to veledimex 10. Use of medications that induce, inhibit, or are substrates of cytochrome p450 (CYP450) 3A4 within 7 days prior to veledimex 11. Use of heparin or acetylsalicylic acid (ASA). The use of systemic heparinization, or any ASA containing medications, is prohibited during active dosing with veledimex. Prophylactic heparin SC, per institutional protocol, or heparin when used for maintaining patency of an access port of a PICC line is permitted. 12. Presence of any contraindication for a neurosurgical procedure 13. Unstable or clinically significant concurrent medical condition that would jeopardize the safety of a subject and/or their compliance with the protocol