Brief Summary
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 chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells.
Intervention / Treatment
- Drug: Tagraxofusp
- Drug: Venetoclax
- Drug: Azacitidine
Inclusion Criteria:
- Previously untreated with histological confirmation of AML by World Health Organization 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 determined 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%.
- Left ventricular ejection fraction ≤50%.
- 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 and Medical Monitor prior to enrollment.
- ECOG performance status:
- Of 0 to 2 for participants if ≥75 years of age, or
- Of 0 to 3 for participants ≥18 to 74 years of age.