A Study to Assess How Well the Study Medicine IPN60340 Works in Combination With Azacitidine and Venetoclax, Compared to Placebo in Combination With Azacitidine and Venetoclax, in Participants With Newly Diagnosed Acute Myeloid Leukemia Who Cannot Receive Intensive Chemotherapy

Inclusion criteria

• Participant must be 18 years of age or older, at the time of signing the informed consent.
• Have newly diagnosed AML, as per WHO 2022 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 1 to 2 for participants ≥75 years of age, or 1 to 3 for participants <75 years of age
• Participants must be considered ineligible for intensive chemotherapy, due to age or comorbidities,
• Adequate organ function as indicated in the protocol
• Contraceptive use by participant or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials.
• Signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Current diagnosis of:

I. Acute promyelocytic leukemia (APL) II. Active or uncontrolled central nervous system (CNS) leukemia III. Any γ9δ2TC neoplasm

• History of myeloproliferative neoplasms (MPN) including primary myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia, or MDS/MPN as per WHO 2022 or treatment-related AML
• History of other malignancy within the last 2 years.
• Rapidly progressing disease in the opinion of the clinical investigator which may preclude treatment in this study.
• History of clinically significant or uncontrolled cardiac disorders, within 6 months prior to Cycle 1 Day 1 (C1D1)
• White blood cell (WBC) count >25 × 10^9/L . Cytoreduction can be used before C1D1 and beyond as needed to keep WBC < 25 × 10^9.
• Participants with severe hepatic impairment, e.g., Child-Pugh C, are excluded.
• Major surgery within 4 weeks prior to C1D1 or planned during the foreseeable duration of the study.
• Any gastrointestinal disorder or malabsorption syndrome that may impair absorption of venetoclax
• Uncontrolled or severe bacterial, fungal, viral, and/or parasitic infections treated with therapeutic oral or intravenous anti-infective agents. Prophylactic antimicrobials are allowed.
• Uncontrolled human immunodeficiency virus (HIV) disease will be excluded. Participants on anti-retroviral therapy should be included as long as their disease is under control, taking precautions to modify their highly active antiretroviral therapy (HAART) regimen to minimize drug interactions.
• Presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) at screening or within 3 months prior to randomization.

NOTE: Participants with known positive HBsAb may be randomized provided they are hepatitis B-vaccinated and have negative HBsAg and HBcAb.

• Positive hepatitis C antibody test result at screening or within 3 months of randomization unless HCV-RNA negative test is documented.

NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can be enrolled if a confirmatory negative hepatitis C ribonucleic acid (RNA) test is obtained.

• Participant has received strong and/or moderate cytochrome P450 (CYP)3A inducers within 7 days prior to the initiation of study treatment.
• Participant is unable to swallow capsules or tablets
• Prior treatment with hypomethylating agents, chemotherapy, B-cell lymphoma protein (BCL) 2 inhibitors, clinical trial therapy, cellular therapy or allogenic hematopoietic cell transplantation (HCT) for MDS.
• Treatment with systemic corticosteroids of >10 mg/day prednisone (or equivalent) or other systemic immunosuppressive medications within 5 half-lives prior to C1D1, or anticipated requirement for systemic immunosuppressive medications during the study.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator [or medical monitor], contraindicates participation in the study.