Inclusion Criteria:
* Participants must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
* Participant must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study.
* Participant must be 18 years of age or older
* Participants with pathologically confirmed grade 2, 3 or 4 gliomas with IDH mutation (confirmed by IDH R132H immunohistochemistry or IDH1/IDH2 next generation sequencing) who have progressive tumor and have had previous exposure to alkylating agents.
* Participants must have measurable disease, defined as at least one enhancing tumor lesion that can be accurately measured in at least one dimension as ≥ 10mm x 10mm on brain MRI. See 13.2 Disease Parameters for more information regarding evaluation of measurable disease. Patients with non-enhancing measureable disease may be eligible upon discussion with and approval by the CUMC PI.
* Availability of baseline frozen tumor or formalin-fixed paraffin-embedded (FFPE) tumor block.
* Karnofsky Performance Score (KPS) of 60 and above
* Adequate bone marrow, kidney and liver function as defined below:
i) White blood count (WBC) ≥ 3000/microliter (uL) ii) Neutrophils ≥ 1500/uL iii) Absolute lymphocyte count ≥ 500/uL iv) Platelets ≥ 100x103 /uL v) Hemoglobin ≥ 9.0g/dL vi) Serum creatinine ≤ 1.5x upper limit of normal (ULN) or calculated creatinine clearance (CrCl)\> 50 mL/min (using the Cockcroft-Gault formula)
1. Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
2. Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL vi) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x ULN vii) Total bilirubin (TBILI) ≤ 1.5 x ULN (except participants with Gilbert Syndrome who must have a total bilirubin level of \< 3.0xULN)
* Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) within 24 hours prior to the start of study drug
* Women must not be pregnant or breastfeeding
* WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 5 months after the last dose of study treatment (i.e., 30 days (duration of ovulatory cycle) plus the time required for the investigational drug to undergo approximately five half-lives.)
* Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment with nivolumab and 7 months after the last dose of study treatment (i.e., 90 days (duration of sperm turnover) plus the time required for the investigational drug to undergo approximately five halflives.)
* Azoospermic males are exempt from contraceptive requirements. WOCBP who are continuously not heterosexually active are also exempt from contraceptive requirements, but still must undergo pregnancy testing.
* Investigators shall counsel WOCBP, and male participants who are sexually active with WOCBP, on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception, which have a failure rate of \< 1% when used consistently and correctly.
* At a minimum, participants must agree to use 1 highly effective method of contraception
Exclusion Criteria:
* Participants with an active, known, or suspected autoimmune disease.
* Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
* Participants with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Dose of dexamethasone ≤ 4 mg/day or equivalent is allowed at the study entry for brain tumor edema
* Participants who have received chemotherapy or experimental agents within 4 weeks (except for 6 weeks for nitrosoureas and 23 days for temozolomide) and radiotherapy within 12 weeks of the first dose of the study treatment.
* Prior use of PD-1, PD-L1, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors or exposure to other checkpoint inhibitors.
* Prior exposure to bevacizumab or other vascular endothelial growth factor (VEGF) or VEGFR inhibitors.
* Any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection, and/or detectable virus
* History of severe allergy or hypersensitivity to nivolumab components
