RNA Lipid Particles Targeting Pediatric Recurrent Intracranial Malignancies and Other systEmic Solid Tumors

Eligibility Criteria

• * Patients with M+ disease without gliomatosis cerebri (see definition under exclusion criteria) ARE eligible.
• * Recurrent pHGG involving the midline structures other than those intrinsically located within the pons ARE eligible.
• * Patients with mismatch repair deficient (MMRD) tumors refractory to immune checkpoint inhibitors ARE eligible.
• * Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• * Participants with post-surgical neurological deficits should have deficits that are stable for a minimum of 2 week prior to enrollment.
• * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: ≥ 21 days after the last dose of myelosuppressive chemotherapy. If questions, the agent and duration can be discussed with the study chair.
• * Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or ANC counts): ≥ 14 days after the last dose of agent. If questions, the agent and duration can be discussed with the study chair.
• * Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to Grade ≤ 1.
• * Corticosteroids: All systemically administered corticosteroids must be stable or decreasing for ≥ 1 week prior to enrollment, with a maximum dexamethasone dose of 2.8 mg/m2/day. Corticosteroid physiologic replacement therapy for management of pituitary/adrenal axis insufficiency and/or topical administration (e.g. inhaled or dermatologic) is allowed.
• * Hematopoietic growth factors: ≥14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or ≥7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur.
• * Interleukins, Interferons, and Cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon, or cytokines.
• * Stem cell infusions (with or without TBI):
• * Autologous stem cell infusion including boost infusion: ≥ 30 days.
• * Cellular Therapy: ≥ 42 days after the completion of any type of cellular therapy (e.g., modified T cells, NK cells, dendritic cells, etc.)
• * XRT/External Beam Irradiation, including Protons: ≥ 90 days after local XRT unless recurrence is a new enhancement on MRI outside the radiation treatment field; ≥ 150 days after TBI, craniospinal XRT or if radiation to ≥ 50% of the pelvis.
• * Radiopharmaceutical therapy (e.g., radiolabeled antibody): ≥ 42 days after systematically administered radiopharmaceutical therapy.
• * Other therapeutic clinical trials: ≥ 14 days after last dose of investigational agent, unless otherwise defined above.
• * Prior use of RNA-LP therapy: Patients must not have received prior exposure to pp65-directed therapy or any RNA-LP therapy.
• * Absolute neutrophil count (ANC) ≥ 1,000/µl
• * Platelets ≥ 100,000/µl (transfusion-independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment)
• * Hemoglobin ≥ 8 g/dL (transfusion-independent, defined as not receiving packed red blood cell transfusions for at least 7 days prior to enrollment)
• * A creatinine based on age/gender
• * Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m2
• * Total bilirubin ≤ 3x institutional upper limits of normal for age
• * ALT ≤ 5x institutional upper limits of normal for age
• * AST ≤ 5x institutional upper limits of normal for age Adequate pulmonary function defined as baseline pulse oximetry of at least 92% on room air.
• * Women of childbearing potential must agree to use of at least 2 forms of acceptable contraceptive methods or abstinence to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
• * Men with female partners of childbearing potential must agree to use of at least 2 forms of acceptable contraceptive methods or abstinence throughout the study and should avoid conceiving children for at least 24 weeks following the last dose of study drug.