Study of AG-120 (Ivosidenib) vs. Placebo in Combination With Azacitidine in Patients With Previously Untreated Acute Myeloid Leukemia With an IDH1 Mutation

Inclusion Criteria:

1. Be ≥ 18 years of age.

2. Have previously untreated AML, defined according to WHO criteria, with ≥ 20% leukemic
blasts in the bone marrow. Subjects with extramedullary disease alone (ie, no
detectable bone marrow and no detectable peripheral blood AML) are not eligible for
the study.

3. Have an isocitrate dehydrogenase 1 (IDH1) mutation

4. Have an ECOG Performance Status score of 0 to 2.

5. Have adequate hepatic function

6. Have adequate renal function

7. Have agreed to undergo serial blood and bone marrow sampling.

8. Be able to understand and willing to sign an informed consent form (ICF).

9. Be willing to complete Quality of Life assessments during the study

10. If female with reproductive potential, must have a negative serum pregnancy test prior
to the start of study therapy. Females of reproductive potential, as well as fertile
men and their female partners of reproductive potential, must agree to use 2 effective
forms of contraception.

Exclusion Criteria:

1. Are candidates for and willing to receive intensive IC for their AML.

2. Have received any prior treatment for AML with the exception of hydroxyurea.

3. Have received a hypomethylating agent for myelodysplastic syndrome (MDS).

4. Subjects who had previously received an experimental agent for MDS may not be
randomized until a washout period has elapsed since the last dose of that agent.

5. Have received prior treatment with an IDH1 inhibitor.

6. Have a known hypersensitivity to any of the components of AG-120, matched placebo, or
azacitidine.

7. Are female and pregnant or breastfeeding.

8. Have an active, uncontrolled, systemic fungal, bacterial, or viral infection without
improvement despite appropriate antibiotics, antiviral therapy, and/or other
treatment.

9. Have a prior history of cancer other than MDS or myeloproliferative disorder, unless
the subject has been free of the disease for ≥ 1 year prior to the start of study
treatment.

10. Have had significant active cardiac disease within 6 months prior to the start of
study treatment

11. Have any condition that increases the risk of abnormal ECG or cardiac arrhythmia

12. Have a condition that limits the ingestion or absorption of drugs administered by
mouth

13. Have uncontrolled hypertension (systolic blood pressure [BP] > 180 mmHg or diastolic
BP > 100 mmHg).

14. Have clinical symptoms suggestive of active central nervous system (CNS) leukemia or
known CNS leukemia.

15. Have immediate, life-threatening, severe complications of leukemia, such as
uncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminated
intravascular coagulation.

16. Have any other medical or psychological condition deemed by the Investigator to be
likely to interfere with the subject's ability to give informed consent or participate
in the study.