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

About

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 chemotherapy.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

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.