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 dosethe amount of medication taken 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 Oncologythe study, diagnosis and treatment of cancer 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 Monitorto check on, keep track of 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.