A Study Evaluating the Safety and Efficacy of Idasanutlin in Combination With Cytarabine and Daunorubicin in Patients Newly Diagnosed With Acute Myeloid Leukemia (AML) and the Safety and Efficacy of Idasanutlin in the Maintenance of First AML Complete Remission

Inclusion Criteria:

Inclusion Criteria for All Study Phases:

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2

- Adequate hepatic and renal function

- For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive measures, and agreement to refrain from
donating eggs with a failure rate of <1% per year during the treatment period and for
at least 6 months after the final dose of idasanutlin, cytarabine, or daunorubicin.
Women must refrain from donating eggs during this same period.

- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive, measures, and agreement to refrain from donating sperm that together
result in a failure rate of <1% per year during the treatment period and for 6 months
after the final dose of idasanutlin, cytarabine, or daunorubicin. Men must refrain
from donating sperm during this same period.

Inclusion Criteria for Patients in the Dose-Escalation and Expansion Phases:

- Documented/confirmed newly diagnosed acute myeloid leukemia (AML) not previously treated
according to World Health Organization (WHO)

Inclusion Criteria for Patients in the Post-Consolidation Phase:

- Documented/confirmed AML according to WHO in remission after induction, within 21 days of
end of last chemotherapy consolidation cycle, and were minimum residual disease (MRD)
positive at the end of induction as per local laboratory assessment

Exclusion Criteria:

Exclusion Criteria for All Study Phases:

- Clinical evidence of central nervous system (CNS) leukemia

- Any Grade ≥2 non-hematologic toxicities prior to starting therapy

- Current treatment with any other investigational or commercial agents or therapies
administered with the intention to treat their malignancy with the exception of
hydroxyurea (HU) or 6-mercaptopurine (6-MP)

- Treatment-related AML

- Acute promyelocytic leukemia

- History of other malignancy that could affect compliance with the protocol or
interpretation of results

- Any severe and/or uncontrolled medical conditions or other conditions that could
affect their participation in the study, impair the ability of the investigator to
evaluate the patient, or impair the patient's ability to complete the study

- Echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan showing ejection
fraction ≤40%

- Non-malignant medical illnesses that are uncontrolled or whose control may be
jeopardized by this study treatment, such as hereditary coagulation disorders,
insulin-dependent diabetes mellitus not optimally controlled with medical management
(e.g., presence of ketoacidosis), or active GI conditions affecting absorption

- Infection considered by the investigator to be clinically uncontrolled or of
unacceptable risk to the patient upon the induction of neutropenia, that is, patients
who are or should be on antimicrobial agents for the treatment of active infection

- Febrile patients within 72 hours of study treatment initiation

- Patients with a history of active or chronic infectious hepatitis unless serology
demonstrates clearance of infection

- Patients who are unable to interrupt treatment with moderate to strong CYP2C8 inducers
and inhibitors

- Patients who are unable to temporarily interrupt treatment with oral or parenteral
anticoagulants/anti-platelet agents during treatment phase

- Patients who have a history of clinically significant liver cirrhosis

- Patients with extramedullary AML with no evidence of systemic involvement

- Pregnant or breastfeeding patients

- Known history of HIV-positive status

- Patients who might refuse to receive blood products and/or have a hypersensitivity to
blood products

- Prior treatment with an MDM2 antagonist

- Patients with clinically relevant QTc prolongation, a family history of long QT
syndrome

Exclusion Criteria for Patients in the Phase Ib Dose-Escalation Phase:

- Adverse risk patients as per European LeukemiaNet (ELN) 2017 criteria

Exclusion Criteria for Patients in Phase Ib Post-Consolidation Phase:

- Any ongoing Grade ≥2 hematologic adverse events prior to starting therapy

- Previous hematopoietic stem cell transplant (HSCT)

Exclusion Criteria for Patients in the Dose-Escalation Phase and Patients in the
Favorable/Intermediate-Risk Cohort of the Expansion Phase:

- Secondary AML, defined as AML evolving from antecedent hematologic disorder (AHD)