A Phase II Multicenter Open-label Trial of Tagraxofusp (Tag) in Combination With Venetoclax and Azacitidine (Ven/Aza) in Adults With Previously Untreated CD123+ Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy.

Key Inclusion Criteria: - Previously untreated with histological confirmation of AML by World Health Organization 2022 criteria and are ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age, or comorbidity. - Participant has any level of CD123 expression on blasts confirmed centrally by flow cytometry. - Must be considered ineligible for intensive chemotherapy, defined by the following: - ≥75 years of age; or - ≥18 to 74 years of age with at least 1 of the following comorbidities: - Eastern Cooperative Oncology Group (ECOG) performance status of 2 or 3. - Diffusing capacity of the lung for carbon monoxide of ≤65% or forced expiratory volume in 1 second ≤65%. - Baseline creatinine clearance ≥30 to <45 milliliters/minute calculated by the Cockcroft Gault formula or measured by 24-hour urine collection. - Hepatic disorder with total bilirubin >1.5 x upper limit of normal. - Any other comorbidity that the investigator judges to be incompatible with intensive chemotherapy must be reviewed and approved by the Sponsor. - ECOG performance status: - 0 to 2 for participants ≥75 years of age, or - 0 to 3 for participants ≥18 to 74 years of age. Key Exclusion Criteria: - Participant has received prior therapy for AML. - Willing and able to receive standard induction therapy. - Treatment for an antecedent hematologic disease with a hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine, intensive chemotherapy, chimeric antigen receptor-T therapy, or other experimental therapies. - AML with central nervous system involvement. Note: Other inclusion/exclusion criteria may apply.