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

Received systemic anticancer therapy or radiotherapy \< 21 days prior to their first day of study drug administration

Received an investigational agent \< 14 days prior to their first day of study drug administration. In addition, the first dose of AG-221 should not occur before a period ≥ 5 half-lives of the investigational agent has elapsed

Subjects taking the following sensitive cytochrome P450 (CYP) substrate medications that have a narrow therapeutic range are excluded from the study unless they can be transferred to other medications prior to enrolling: paclitaxel (CYP2C8), warfarin, phenytoin (CYP2C9), S-mephenytoin (CYP2C19), thioridazine (CYP2D6), theophylline and tizanidine (CYP1A2)

Subjects taking the P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) transporter-sensitive substrates digoxin and rosuvastatin should be excluded from the study, unless they can be transferred to other medications prior to enrolling. study unless they can be transferred to other medications prior to enrolling

Subjects for whom potentially curative anticancer therapy is available

Pregnant or breastfeeding

Active severe infection that required anti-infective therapy or with an unexplained fever \> 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) \< 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of Cycle 1Day 1

History of myocardial infarction within the last 6 months

Subjects with uncontrolled hypertension (systolic blood pressure \> 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, symptomatic, or require therapy to control symptoms; or any radiation, surgery, or other therapy, including to control symptoms, within 2 months of first dose. Subjects with glioma who are on a stable, steroid-dosing regimen prior to screening magnetic resonance imaging (MRI) may be permitted to enroll with Medical Monitor approval

In subjects with AITL, evidence of meningeal or cerebral disease or a history of progressive multifocal leukoencephalopathy

Radiotherapy involving \< 25% of the hematopoietically active bone marrow within 21 days preceding first dose of study treatment

Radiotherapy involving ≥ 25% of the hematopoietically active bone marrow within 42 days preceding first dose of study treatment

What this study is about