Nivolumab for Recurrent or Progressive IDH Mutant Gliomas

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)

• Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL
• 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 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