Key Inclusion Criteria:

* Subject must be ≥18 years of age.
* Subjects must have documented IDH1 R132 gene-mutated advanced hematologic malignancy based 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: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤3.0 × ULN, unless considered due to leukemic disease and serum total bilirubin ≤1.5 x upper limit of normal (ULN), unless considered due to Gilbert's disease 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 filtration rate (GFR)
* Subjects must be recovered from any clinically relevant toxic effects of any prior surgery, radiotherapy, or other therapy intended for the treatment of cancer.
* Female subjects with reproductive potential must have a negative serum pregnancy test within 7 days prior to the start of therapy and on the first day of study drug administration.

Key Exclusion Criteria:

* Subjects who have undergone hematopoietic stem cell transplant (HSCT) within 60 days of the first dose of AG-120, or subjects on immunosuppressive therapy post HSCT at the 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 for ongoing skin GVHD is permitted.)
* Subjects who received systemic anticancer therapy or radiotherapy \<14 days prior to their first day of study drug administration. (Hydroxyurea is allowed prior to enrollment and after the start of AG-120).
* Subjects who received an investigational agent \<14 days prior to their first day of study drug administration.
* Subjects who are pregnant or breastfeeding.
* Subjects with an active severe infection 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).
* Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within approximately 28 days of C1D1.
* Subjects with a history of myocardial infarction within the last 6 months of screening.
* 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 that increase 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 active hepatitis B or C.
* Subjects with clinical symptoms suggesting active central nervous system (CNS) leukemia or known CNS leukemia. Evaluation of cerebrospinal fluid is only required if there is a clinical suspicion of CNS involvement by leukemia during screening.
* Subjects with immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, and/or disseminated intravascular coagulation.