Vorasidenib and a Tumor Specific Peptide Vaccine for the Treatment of Recurrent or Progressive IDH1 Mutant Lower Grade Gliomas

Inclusion Criteria

• Age ≥ 18 years
• IDH1R132H expression in primary tumor * Note: IDH1 mutation status is routinely performed at initial diagnosis for this patient population. If a patient comes to Duke for participation in the trial and previously had IDH1 mutation testing performed elsewhere at initial diagnosis, these test results can be used for assessing eligibility
• Clinical and/or radiographic, recurrent or progressive WHO Grades 2-3 glioma with greater than 2 cm of non-enhancing disease in one plane
• 1st recurrence only
• Signed informed consent
• For patients of child-bearing potential, negative serum pregnancy test at screening
• Patients of childbearing potential and patients that are capable of producing sperm must agree to practice contraception
• Karnofsky Performance Status (KPS) of ≥ 70
• Expected survival of ≥ 12 months
• Recovered from any clinically relevant toxicities associated with any prior surgery for the treatment of glioma unless stabilized under medical management
• Absolute neutrophil count, ≥ 1000 cells/mm^3 (within 2 weeks of enrollment)
• Platelet count, ≥ 100,000 cells/mm^3 (within 2 weeks of enrollment)
• Hemoglobin ≥ 10 g/dL (within 2 weeks of enrollment) (Note: The use of transfusion or other intervention to achieve hemoglobulin (Hgb) ≥ 10 g/dL is acceptable.)
• Blood urea nitrogen (BUN) ≤ 25 mg/dL (within 2 weeks of enrollment)
• Creatinine ≤ 1.7 mg/dL (within 2 weeks of enrollment)
• Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) (within 2 weeks of enrollment)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) at or below normal limits (within 2 weeks of enrollment) Note: An elevation ≤ 1.5 × ULN that is considered not clinically significant by the Investigator will be allowed
• Alkaline phosphatase (ALP) ≤ 2.5 x ULN (within 2 weeks of enrollment)

Exclusion Criteria

• Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years (e.g., carcinoma in situ of the breast, oral cavity, and cervix are all permissible)
• Metastases detected below the tentorium or beyond the cranial vault
• More than 1 cm x 1 cm of enhancing disease on gadolinium contrasted MRI
• Severe, active co-morbidity, defined as follows: * Unstable angina and/or congestive heart failure requiring hospitalization * Myocardial infarction within the last 6 months. * Known Acquired Immune Deficiency Syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition ** Note: Human Immunodeficiency Virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because treatments involved in this protocol may be significantly immunosuppressive. * Major medical illnesses or psychiatric impairments that in the investigator's opinion will prevent administration or completion of protocol therapy.
• Pregnant or lactating patients, due to possible adverse effects on the developing fetus or infant due to study drugs
• 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 arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome)
• 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 to prior HBV infection will be permitted * Note: Patients with chronic HBV that is adequately suppressed by institutional practice will be permitted.
• Patients with active gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band dysphagia, short-gut syndrome, gastroparesis, or other condition that limits the ingestion or gastrointestinal absorption of drugs administered orally * Note: Gastroesophageal reflux disease under medical treatment is allowed
• Patient taking any medications that are CYP2C8, CYP2C9, CYP2C19, or CYP3A substrates with a narrow therapeutic index, CYP3A4 inhibitors or any drugs that prolong the QTc interval * Note: Patients should be transferred to other medications before receiving the first dose of study drug.
• Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry or during participation in the study
• Patients with known hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF), yeast-derived products, or any component of Leukine®
• Allergy or hypersensitivity to the Td vaccine or any component of the Td vaccine
• Known hypersensitivity to any component of vorasidenib
• Prior therapy with mutant IDH1 targeted therapeutics
• Unable to undergo MRI