Study of Orally Administered Enasidenib (AG-221) in Adults With Advanced Solid Tumors, Including Glioma, or Angioimmunoblastic T-cell Lymphoma, With an IDH2 Mutation

Inclusion Criteria

• Subject must be ≥ 18 years of age
• Histologically or cytologically confirmed advanced solid tumor, including glioma, or angioimmunoblastic T-cell lymphoma (AITL) that has recurred or progressed following standard therapy, or that has not responded to standard therapy
• Subjects must be amenable to peripheral blood sampling, urine sampling, and biopsies during the study. Subjects with AITL must also be amenable to serial bone marrow biopsies
• Documented IDH2 gene-mutated disease based on local site testing
• Measurable disease by RECIST v1.1 for subjects with solid tumors without glioma, by modified RANO criteria for subjects with glioma, or by the revised IWG criteria for subjects with AITL
• Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Adequate bone marrow function (subjects other than those with AITL) as evidenced by: absolute neutrophil count ≥ 1.0 ×10^9/L; hemoglobin > 9 g/dL (subjects may be transfused red blood cells to this level.); platelets ≥ 50 × 10^9/L
• Adequate hepatic function as evidenced by: serum total bilirubin ≤ 1.5 × upper limit of normal (ULN), unless considered due to Gilbert's disease, a gene mutation in UGT1A1, or disease involvement, following approval by the Medical Monitor; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) ≤ 2.5 × ULN, with the exception of subjects with bone metastases and/or suspected disease-related liver or biliary involvement, where ALP must be ≤ 5 × ULN
• Adequate renal function as evidenced by: serum creatinine ≤ 2.0 × ULN; OR creatinine clearance > 40 mL/min based on the Cockroft-Gault glomerular filtration rate (GFR) estimation: (140 - Age) x (weight in kg) x (0.85 if female)/72 x serum creatinine
• Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy. Women of childbearing potential as well as fertile men and their partners must agree to abstain from sexual intercourse or to use an effective form of contraception during the study and for 90 days (females and males) following the last dose of AG-221
• Previous allogeneic stem cell transplant is allowed only if subjects are >100 days from stem cell transplant and do not have uncontrolled acute or chronic graft-vs-host disease

Exclusion Criteria

• Received systemic anticancer therapy or radiotherapy 38.5°C during screening visits or on their first day of study drug administration (at the discretion of the Investigator, subjects with tumor fever may be enrolled)
• Known hypersensitivity to any of the components of AG-221
• Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or left ventricular ejection fraction (LVEF) 180 mmHg or diastolic blood pressure > 100 mmHg) are excluded. Subjects requiring 2 or more medications to control hypertension are eligible with Medical Monitor approval.
• Known unstable or uncontrolled angina pectoris
• Known history of severe and/or uncontrolled ventricular arrhythmias
• Heart-rate corrected QT (QTc) interval > 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Subjects with right bundle branch block and a prolonged QTc interval should be reviewed by the Medical Monitor for potential inclusion
• Subjects taking medications that are known to prolong the QT interval
• Known infection with human immunodeficiency virus (HIV) or active hepatitis B or C
• Any other medical or psychological condition, deemed by the Investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study
• Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally
• Subjects with brain metastases that are untreated, s