A Phase III Study Comparing Mesutoclax + Azacitidine Versus Venetoclax + Azacitidine in Untreated Acute Myeloid Leukemia (AML) Patients

Prior treatment

• Prior antitumor treatment for myeloid hematologic malignancies.
• Prior history of chronic myeloid leukemia (CML), myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN).
• Use of strong or moderate CYP3A/P-gp inhibitors or inducers (medications, dietary supplements, etc.) within 5 half-lives before the first dose of investigational product.
• Prior history of central nervous system disorders.

Other illness

• Active hepatitis B virus or hepatitis C virus infection.
• History of immunodeficiency, including positive human immunodeficiency virus (HIV) antibody.
• Diagnosis of another active malignant neoplasm within the past 2 years.
• Severe active infection requiring intravenous antimicrobial therapy.
• History of severe cardiovascular disease.
• History of severe bleeding diathesis.
• Participants whom the investigator judges cannot adhere to the protocol due to uncontrolled medical, psychological, familial, social or geographic conditions; or participants who are unwilling or unable to follow protocol-required procedures.
• Malabsorption syndrome or other conditions that preclude oral administration or may interfere with drug absorption.
• Known hypersensitivity to the active ingredients/excipients of mesutoclax tablets, venetoclax, azacitidine, or mannitol.

Lab values

• Peripheral blood white blood cell count >25×10\^9/L prior to randomization.

Other

• Known central nervous system (CNS) involvement of leukemia.
• Known alcohol or substance dependence.
• Pregnant or breastfeeding female participants.

• Study participants with newly diagnosed AML (excluding acute promyelocytic leukemia [APL]) confirmed per the 2022 World Health Organization (WHO) classification criteria.
• Age ≥65 years; or age ≥18 years and <65 years and ineligible for intensive chemotherapy.
• The participant is expected to have a survival time of at least 12 weeks.
• For participants aged ≥65 years: ECOG Performance Status (PS) 0-2; for participants aged ≥18 years and <65 years: ECOG PS 0-3.
• Participants must have adequate hepatic and renal function.
• Male participants must agree to refrain from unprotected sexual intercourse and sperm donation from the first dose of investigational product through 90 days after the last dose.
• Female participants must meet one of the following: postmenopausal; permanently sterilized; or, for females of reproductive potential, have a negative serum pregnancy test within 7 days prior to the first study dose. Females of reproductive potential must agree to use one highly effective contraceptive method plus a supplementary barrier contraceptive method with their partner from the date of ICF signature until 180 days after the last dose.
• The participant is able to communicate adequately with the investigator and comply with study procedures as specified in the protocol.
• The participant or their legally authorized representative voluntarily provides written informed consent.