Overview
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.
Eligibility
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.