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

Inclusion Criteria:

1. Be ≥ 18 years of age and meet at least 1 of the following criteria definingineligibility for intensive induction chemotherapy (IC): ≥ 75 years old, EasternCooperative Oncology Group Performance Status (ECOG PS) score of 2, severe cardiacdisorder (e.g., congestive heart failure requiring treatment, left ventricularejection fraction (LVEF), ≤50%, or chronic stable angina), severe pulmonary disorder (e.g., diffusing capacity of the lungs for carbon monoxide ≤65% or forced expiratoryvolume in 1 second ≤65%), creatinine clearance <45 mL/minute, bilirubin >1.5 timesthe upper limit of normal (ULN) and/or have any other comorbidity that theInvestigator judges to be incompatible with intensive IC and must be reviewed andapproved by the Medical Monitor before study enrollment.

2. Have previously untreated AML, defined according to World Health Organization (WHO)criteria, with ≥ 20% leukemic blasts in the bone marrow. Participants withextramedullary disease alone (i.e., no detectable bone marrow and no detectableperipheral blood AML) are not eligible for the study.

3. Have an isocitrate dehydrogenase 1 (IDH1) mutation.

4. Have an ECOG PS 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 testprior to the start of study therapy. Females of reproductive potential, as well asfertile men and their female partners of reproductive potential, must agree to use 2effective forms of contraception.

Exclusion Criteria:

1. Are candidates for and willing to receive intensive induction chemotherapy (IC) fortheir 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. Participants who had previously received an experimental agent for MDS may not berandomized 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 withoutimprovement despite appropriate antibiotics, antiviral therapy, and/or othertreatment.

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

10. Have had significant active cardiac disease within 6 months prior to the start ofthe 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 bymouth.

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

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

15. Have immediate, life-threatening, severe complications of leukemia, such asuncontrolled bleeding, pneumonia with hypoxia or sepsis, and/or disseminatedintravascular coagulation.

16. Have any other medical or psychological condition deemed by the Investigator to belikely to interfere with the participant's ability to give informed consent orparticipate in the study.

17. Are taking medications that are known to prolong the QT interval unless they can betransferred to other medications within ≥5 half-lives prior to dosing, or unless themedications can be properly monitored during the study. (If equivalent medication isnot available, heart rate corrected QT interval [QTc] will be closely monitored.)

18. Have a known medical history of progressive multifocal leukoencephalopathy.