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 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.