Targeted LSAM-Cisplatin Infusion in Gliomas, Evaluation of Response

Open-label, dose-escalating, Phase 1/2a trial of Large Surface Area Microparticle (LSAM)-Cisplatin to treat participants with diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), via stereotactic infusion under intraoperative magnetic resonance imaging (MRI) guidance.

Inclusion Criteria: * Aged 3 to ≤ 21 years. * Diagnosis of diffuse midline glioma (DMG), including diffuse intrinsic pontine glioma (DIPG), based on characteristic magnetic resonance imaging (MRI) findings and/or histopathologic confirmation. * Prior radiation treatment must have included focal radiation therapy per institutional standard of care and must have been initiated within 6 weeks of diagnosis. * At least 4 weeks, but no more than 12 weeks, post-completion of radiotherapy treatment. * A standard of care post-radiation magnetic resonance imaging (MRI) performed 4 to 6 weeks after radiation therapy is required for confirmation of eligibility. * Performance status \[Karnofsky Performance Scale or Lansky Performance Score\] within 14 days of Day 1 ≥ 60. * Absence of other significant medical condition. * A legal parent/guardian and/or participant must be able to understand and be willing to sign a written informed consent and/or assent document, as appropriate. Exclusion Criteria: * Untreated symptomatic hydrocephalus at the time of consent, has metastatic or disseminated disease, or leptomeningeal disease. * Magnetic resonance imaging (MRI) findings that preclude stereotactic procedure. * Intercurrent illnesses or conditions which preclude participation: active systemic infections, autoimmune disease requiring systemic immunomodulation, active or uncontrolled seizure disorder, central nervous system (CNS) vasculopathy or aneurysms, Grade ≥3 cardiac dysfunction, Fridericia-corrected QT interval (QTcF) ≥470 ms. * Abnormal organ function: * Renal insufficiency: glomerular filtration rate (GFR) ≤ 60 mL/min/1.73m² (with Schwartz equation) * Hepatic dysfunction: aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 1.5 x upper limit of normal (ULN) and 3 x upper limit of normal (ULN) in the presence of liver metastases; or bilirubin ≤ 1.5 x upper limit of normal (ULN) and 3 x upper limit of normal (ULN) in the presence of Gilbert disease * Bone marrow suppression: * absolute neutrophil count (ANC) \< 1,000/μL * platelets \< 100,000/μL * Coagulopathy or international normalized ratio (INR) \> 1.5 * Receiving any anticoagulants or antiplatelet drugs; any drugs known to cause ototoxicity and nephrotoxicity; receiving any other tumor-directed therapy. * Known allergy or hypersensitivity to the study agent (including cisplatin and diluent components). * Female participants of childbearing potential must not be pregnant or breast-feeding.