A Study of Tagraxofusp in Combination With Venetoclax and Azacitidine in Adults With Untreated CD123+ Acute Myeloid Leukemia Who Cannot Undergo Intensive Chemotherapy

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

This study will be divided into 2 parts (Part 1 and Part 2). Part 1 will evaluate 2 doses of tagraxofusp (9 and 12 micrograms/kilogram/day [μg/kg/day]), used in combination with venetoclax and azacitidine, to determine the dose for Part 2. This determined dose, in combination with venetoclax and azacitidine, will then be further evaluated in Part 2 in 2 cohorts (TP53 mutated and TP53 wild type). Both parts will be conducted in participants with previously untreated CD123+ 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.

• Participants 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:

    • 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 condition for which the physician judges the participant to be unsuitable for intensive chemotherapy.

• 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.
• Participant is willing and able to receive standard induction therapy.
• Participant has received treatment for an antecedent hematologic disease with a hypomethylating agent, venetoclax, tagraxofusp, purine analogue, cytarabine, intensive chemotherapy, SCT, chimeric antigen receptor-T therapy, or other experimental therapies.
• Participant has AML with central nervous system involvement.

Note: Other inclusion/exclusion criteria may apply.