ViCToRy: Vorasidenib in Combination With Tumor Specific Peptide Vaccine for Recurrent IDH1 Mutant Lower Grade Gliomas

Inclusion Criteria:

1. Age ≥ 18 years

2. IDH1R132H expression in primary tumor

3. Clinical and/or radiographic, progressive Grade 2-3 glioma with greater than 2 cm ofnon-enhancing disease in one plane.

4. 1st recurrence only

5. Signed informed consent

6. For females of child-bearing potential, negative serum pregnancy test at screening

7. Women of childbearing potential and male participants must agree to practicecontraception

8. Karnofsky Performance Status (KPS) of ≥ 70

9. Expected survival of ≥ 12 months

10. Recovered from any clinically relevant toxicities associated with any prior surgeryfor the treatment of glioma unless stabilized under medical management

11. Complete Blood Count (CBC)/differential with adequate bone marrow function asdefined below within 2 weeks of enrollment:

12. Absolute neutrophil count (ANC) ≥ 1000 cells/mm3

13. Platelet count ≥ 100,000 cells/mm3

14. Hemoglobin (Hgb) ≥ 10 g/dl (Note: The use of transfusion or other interventionto achieve Hgb ≥ 10 g/dl is acceptable.)

15. Adequate renal function as defined below within 2 weeks of enrollment:

16. Blood urea nitrogen (BUN) ≤ 25 mg/dl

17. Creatinine ≤ 1.7 mg/dl

18. Adequate hepatic function as defined below within 2 weeks of enrollment:

19. Bilirubin ≤ 2.0 mg/dl

20. Alanine transaminase (ALT) ≤ 3 x normal range

21. Aspartate aminotransferase (AST) ≤ 3 x normal range

Exclusion Criteria:

1. Prior invasive malignancy (except for non-melanomatous skin cancer) unless diseasefree for ≥ 3 years (e.g., carcinoma in situ of the breast, oral cavity, and cervixare all permissible)

2. Metastases detected below the tentorium or beyond the cranial vault

3. More than 1 cm X 1 cm of enhancing disease on gadolinium contrasted MRI imaging

4. Severe, active co-morbidity, defined as follows:

5. Unstable angina and/or congestive heart failure requiring hospitalization

6. Myocardial infarction within the last 6 months.

7. Known Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers forDisease Control and Prevention (CDC) definition (Note: human immunodeficiencyvirus [HIV] testing is not required for entry into this protocol. The need toexclude patients with Acquired Immunodeficiency Syndrome (AIDS) from thisprotocol is necessary because treatments involved in this protocol may besignificantly immunosuppressive.)

8. Major medical illnesses or psychiatric impairments that in the investigator'sopinion will prevent administration or completion of protocol therapy.

9. Pregnant or lactating women, due to possible adverse effects on the developing fetusor infant due to study drug

10. Patients with a heart-rate corrected QT interval using Fridericia's formula (QTcF) ≥ 450 msec or other factors that increase the risk of QT prolongation or arrhythmicevents (e.g., heart failure, hypokalemia, family history of long QT intervalsyndrome)

11. Patients with known active hepatitis B virus (HBV) or hepatitis C virus (HCV)infection. Subjects with a sustained viral response to HCV treatment or immunity toprior HBV infection will be permitted (Note: Patients with chronic HBV that isadequately suppressed by institutional practice will be permitted.)

12. Patients with active gastrointestinal disease, chronic diarrhea, previous gastricresection or lap band dysphagia, short-gut syndrome, gastroparesis, or othercondition that limits the ingestion or gastrointestinal absorption of drugsadministered orally (Note: Gastroesophageal reflux disease under medical treatmentis allowed.)

13. Patient taking any medications that are CYP3A or CYP2C9 substrates with a narrowtherapeutic index (Note: Patients should be transferred to other medications beforereceiving the first dose of study drug.)

14. Patients treated on any other therapeutic clinical protocols within 30 days prior tostudy entry or during participation in the study

15. Patients with known hypersensitivity to GM-CSF, yeast-derived products, or anycomponent of Leukine®

16. Allergy or hypersensitivity to tetanus vaccine or any component of the tetanusvaccine.

17. Known hypersensitivity to any component of vorasidenib

18. Prior therapy with mIDH1 targeted therapeutics

19. Unable to undergo MRI imaging