Pre-Registration Eligibility Criteria (See Section 3.2)

-Histologic dx of astrocytoma, IDH-mutant (CNS WHO grade 3)

-Available diagnostic slides for central review

-Tissue available for central biomarker testing (CDKN2A/B and1p/19q

co-deletion [all patients], and IDH1/IDH2 [if needed]); see Section 6.2.

Registration Eligibility Criteria (See Section 3.3)

-Centrally-confirmed diagnosis of astrocytoma, IDH-mutant (CNS

WHO grade 3)

-Presence of IDH1 p.R132 or IDH2 p.172 mutation, confirmed by

central review of IHC stain or molecular testing results, with central

confirmation of equivocal results

-Absence of CDKN2A/B homozygous deletion and whole arm 1p/19q

co-deletion (i.e. intact 1p/19q) by central testing

-No evidence of spinal or leptomeningeal disease

• No prior chemotherapy, cranial irradiation, IDH-inhibitor therapy,

radiotherapy, vaccine therapy, small-molecule therapy, or laser

ablation.

-Prior diagnostic surgery/resection/biopsy ≤ 8 weeks of registration.

-Planned radiotherapy and adjuvant chemotherapy.

-Age ≥ 12 years

-ECOG Performance Status ≤2 (or KPS ≥ 60%)

-Not pregnant and not nursing; for women of childbearing potential only, a negative pregnancy test done ≤ 14 days

prior to registration is required.

-Women and men of reproductive potential should agree to abstain from sexual intercourse or use two highly

effective methods of birth control, at least one of which must be a barrier method, throughout their participation in

this study and for at least 90 days after the last dose of vorasidenib (see Section 3.3.9).

-No severe or intercurrent illness, no active infection that requires systemic anti-infective therapy, and no active

infection with an unexplained fever >38.5°C within 7 days prior to registration.

-Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to

interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

-Patients must be able to tolerate or undergo an MRI.

-Patients with known HIV infection on effective anti-retroviral therapy with undetectable viral load within 6 months

prior to registration are eligible for this trial.

-For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable

on suppressive therapy, if indicated.

-Patients with hx of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV

infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

-No significant active cardiac disease within 6 months prior to registration, including NYHA Functional

Classification Class III or IV CHF, myocardial infarction, unstable angina, and/or stroke. To be eligible for this trial,

patients should be class 2B or better.

-No hx of significant (grade ≥2) intratumoral or peri-tumoral hemorrhage.

-No known active inflammatory gastrointestinal disease, chronic diarrhea, prior gastric resection or lap band

dysphagia, short-gut syndrome, gastroparesis, or other condition causing an inability to swallow oral formulations of

agents. Gastroesophageal reflux disease under medical treatment is allowed.

-No known hypersensitivity to any of the components of vorasidenib or temozolomide.

-No other acute or chronic medical condition or laboratory abnormality that may increase the risk associated with

study participation or protocol therapy administration or may interfere with the interpretation of study results and, in

the judgment of the Investigator, would make the patient inappropriate for entry into this study.

-No concurrent use of other investigational agents.

-No concurrent use of alternating tumor treating field (TTField) therapy.

Required Initial Laboratory Values (see

Section 3.3.7):

ANC: ≥ 1,500/mm3

Hemoglobin: ≥ 9 g/dL

Platelet Count: