Entrectinib as a Single Agent in Upfront Therapy for Children <3 Years of Age With NTRK1/2/3 or ROS1-FUSED CNS Tumors

Inclusion Criteria: Screening Phase * Age from birth to age \<3 years at the time of diagnosis (date of surgical resection/biopsy) * Participant with presumed newly diagnosed tumor in the supratentorial compartment * Patient must have measurable disease based on RAPNO criteria * ≤84 days since surgery (resection or biopsy) * Available tumor tissue for central review * Parent/guardian has the ability to understand and the willingness to sign a written informed consent document according to institutional guidelines Exclusion Criteria: Screening Phase * Previous exposure to cytotoxic chemotherapy or radiotherapy Inclusion Criteria: COHORT 1 * Patients must be \<3 years of age at the time of diagnosis (date of surgical resection/biopsy) * High-grade glioma (World Health Organization \[WHO\] grade III or IV) harboring NTRK1/2/3 or ROS1 gene fusions as determined by central pathology review * Patients must have measurable disease as defined by RAPNO criteria * Patients are eligible at the time of diagnosis, prior to any exposure to chemotherapy, targeted therapy, immunotherapy, cellular therapy or radiation * ≤28 days since study screening * Lansky score ≥50% and a minimum life expectancy of ≥ 12 weeks * Neurologic deficits must have been stable for at least 7 days prior to study enrollment * Hemoglobin ≥ 8 g/dL (without transfusion or erythropoietin use within 7 days prior to enrollment) * Platelet count ≥ 75,000/µL (without transfusion within 7-day period prior to enrollment…