Ivosidenib (AG-120) With Nivolumab in IDH1 Mutant Tumors

Inclusion Criteria

• Be ≥18 years of age.
• Have a histopathological diagnosis (fresh or banked tumor biopsy sample, preferably collected within the last 3 years) of an advanced solid tumor for which curative treatment is not available and have undergone appropriate standard of care treatment options (in the opinion of the treating investigator).
• Have a documented IDH1 gene-mutated disease (from a fresh tumor biopsy or the most recent banked tumor tissue available) based on CLIA certified sequencing (R132C/L/G/H/S mutation variants tested).
• For glioma, must have both 1) contrast enhancing disease and 2) WHO 2016 grade II
• Have an ECOG PS score of 0 or 1 (Appendix 11.1)
• Have at least one evaluable and measurable lesion as defined by RECIST v1.1 (solid tumors) or Response Assessment in Neuro-Oncology (RANO) Criteria (glioma).
• Have recovered from toxicities associated with prior anticancer therapy to baseline or ≤ grade 1 unless stabilized under medical management per investigator.
• Have adequate bone marrow function as evidenced by:
• Absolute neutrophil count ≥ 1, 500/mm3 or 1.5 × 109/L
• Hemoglobin ≥ 8 g/dL
• Platelets ≥ 100, 000/mm3 or 100 × 109/L
• Have adequate hepatic function as evidenced by:
• Serum total bilirubin ≤ 2 × upper limit of normal (ULN), unless considered due to Gilbert's disease
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5 × ULN in the presence of liver metastases (or primary hepatic tumor) OR ≤ 2× ULN within glioma patients
• Have adequate renal function as evidenced by:
• Serum creatinine 10 mg prednisone daily or equivalent at time of first dose of study treatment.
• Participants must not have active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroids replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Participants must not have a known history of non-infectious pneumonitis that required steroids for treatment.
• Participants must not have evidence of interstitial lung disease.
• For solid tumor patients, have known symptomatic brain metastases requiring steroids. Participants with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study entry, have discontinued corticosteroid treatment for these metastases for at least 1 week and have radiographically stable disease for at least 1 month prior to study entry.
• Have a history of another primary cancer that is active requiring treatment, progressing or for which the treating investigator believes will make disease assessment unreliable.
• Have evidence of intracranial or intra-tumoral hemorrhage either by MRI or computed tomographic (CT) scan. Participants with resolving post-surgical changes, punctate hemorrhage, or hemosiderin are eligible.
• Underwent major surgery within 4 weeks of Day 1 or have not recovered from post-surgery toxicities.
• Are pregnant or breastfeeding.
• Are taking known strong CYP3A4 inducers or sensitive CYP3A4 substrate medications with a narrow therapeutic window (Appendix 0), unless they can be transferred to other medications within ≥5 t1/2 prior to dosing.
• Are taking P-glycoprotein (P-gp) transporter-sensitive substrate medications with a narrow therapeutic window (Appendix 0), unless they can be transferred to other medications within ≥ 5 t1/2 prior to administration of study treatment.
• Have an active infection requiring systemic anti-infective therapy or with an unexplained fever > 38.5°C within 7 days of Day 1 (at the discretion of the treating investigator) participants with tumor fever may be enrolled).
• Have any known hypersensitivity to any of the components of ivosidenib or nivolumab.
• Have significant