Study of Orally Administered AG-120 in Subjects With Advanced Hematologic Malignancies With an IDH1 Mutation

Key Inclusion Criteria:

• Subject must be ≥18 years of age.

• Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancybased on local or central evaluation.

• Subjects must be amenable to serial bone marrow biopsies, peripheral blood sampling,and urine sampling during the study.

• Subjects must have ECOG PS of 0 to 2.

• Platelet count ≥20,000/µL (Transfusions to achieve this level are allowed).

• Subjects must have adequate hepatic function as evidenced by: Aspartateaminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic disease and serum totalbilirubin ≤1.5 x upper limit of normal (ULN), unless considered due to Gilbert'sdisease or leukemic disease

• Subjects must have adequate renal function as evidenced by a serum creatinine ≤2.0 ×ULN or creatinine clearance >40mL/min based on Cockroft-Gault glomerular filtrationrate (GFR)

• Subjects must be recovered from any clinically relevant toxic effects of any priorsurgery, radiotherapy, or other therapy intended for the treatment of cancer.

• Female subjects with reproductive potential must have a negative serum pregnancytest within 7 days prior to the start of therapy and on the first day of study drugadministration.

Key Exclusion Criteria:

• Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 daysof the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT atthe time of screening, or with clinically significant graft-versus-host disease (GVHD). (The use of a stable dose of oral steroids post HSCT and/or topical forongoing skin GVHD is permitted.)

• Subjects who received systemic anticancer therapy or radiotherapy <14 days prior totheir first day of study drug administration. (Hydroxyurea is allowed prior toenrollment and after the start of AG-120).

• Subjects who received an investigational agent <14 days prior to their first day ofstudy drug administration.

• Subjects who are pregnant or breastfeeding.

• Subjects with an active severe infection or with an unexplained fever >38.5°C duringscreening visits or on their first day of study drug administration (at thediscretion of the Investigator, subjects with tumor fever may be enrolled).

• Subjects with New York Heart Association (NYHA) Class III or IV congestive heartfailure or LVEF <40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scanwithin approximately 28 days of C1D1.

• Subjects with a history of myocardial infarction within the last 6 months ofscreening.

• Subjects with a known unstable or uncontrolled angina pectoris.

• Subjects with a known history of severe and/or uncontrolled ventricular arrhythmias.

• Subjects with known unstable or uncontrolled angina pectoris.

• Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors thatincrease the risk of QT prolongation or arrhythmic events.

• Patients taking medications that are known to prolong the QT interval

• Subjects with known infection with human immunodeficiency virus (HIV) or activehepatitis B or C.

• Subjects with clinical symptoms suggesting active central nervous system (CNS)leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only requiredif there is a clinical suspicion of CNS involvement by leukemia during screening.

• Subjects with immediately life-threatening, severe complications of leukemia such asuncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminatedintravascular coagulation.