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)
* Absolute neutrophil count \>1,000/µL
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5x the upper limit of normal (ULN)
* Bilirubin ≤ 1.5 x ULN
* Adequate renal function as defined by the following age-based serum creatinine concentrations:
* 0 to \<1 year: 0.5 mg/dL
* 1 to \<2 years: 0.6 mg/dL
* 2 to 3 years: 0.8 mg/dL
* Adequate cardiac function as defined by electrocardiogram (ECG) with Fridericia's corrected QT interval (QTc) ≤ 450 msec and echocardiogram left ventricular ejection fraction (LVEF) \>50%
* Screening and enrollment consents signed
* Willingness and ability to comply with treatment plan, scheduled visits, laboratory tests and other study procedures
Inclusion Criteria: COHORT 2
* Patients must be \<3 years of age at the time of diagnosis (date of surgical resection/biopsy)
* CNS tumor other than HGG 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);
* Absolute neutrophil count \>1,000/µL.
* ALT and ALT ≤2.5x the upper limit of normal (ULN)
* Bilirubin ≤ 1.5 x ULN
* Adequate renal function as defined by the following age-based serum creatinine concentrations:
* 0 to \<1 year: 0.5 mg/dL
* 1 to \<2 years: 0.6 mg/dL
* 2 to 3 years: 0.8 mg/dL
* Adequate cardiac function as defined by ECG with QTc ≤ 450 msec and echocardiogram LVEF \>50%
* Screening and enrollment consents signed
* Willingness and ability to comply with treatment plan, scheduled visits, laboratory tests and other study procedures
Exclusion Criteria: COHORT 1 AND 2
* Clinically significant medical disorder that could compromise the ability to tolerate study therapy or would interfere with the study procedures or results history
* History of recent (3 months) symptomatic congestive heart failure
* Known active, uncontrolled infection (bacterial, fungal, or viral)
* Receiving enzyme inducing antiepileptic drugs (EIAEDs)
* Any prior cancer therapy including chemotherapy (excluding Bridging Chemotherapy Cycle), targeted therapy, immunotherapy, cellular therapy, or radiation
* Receiving another investigational agent concurrently
* Surgery within 2 weeks prior to treatment enrollment
* Patients with known hypersensitivity to excipients of the investigational medicinal product
* Active gastrointestinal disease or malabsorption disorder (e.g. Crohn's disease, ulcerative colitis, short-gut syndrome) that would impair drug absorption
* Inability to take medication enterally