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

Stemline Therapeutics

Status and phase: Enrolling; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Venetoclax; Drug: Azacitidine; Drug: Tagraxofusp

Study type: Interventional

Funder types: Industry

Identifiers

NCT06456463

STML-401-0423

U1111-1290-9087 (Other Identifier)

2024-514660-48-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

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.

Enrollment: 76 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key 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.

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 any of the following:

  • 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.

Note: Other inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

76 participants in 4 patient groups

Part 1 - Tagraxofusp (9 μg/kg/day)

Experimental group

Description:

Participants will receive tagraxofusp in combination with venetoclax and azacitidine.

Treatment:

Drug: Tagraxofusp

Drug: Azacitidine

Drug: Venetoclax

Part 1 - Tagraxofusp (12 μg/kg/day)

Experimental group

Description:

Participants will receive tagraxofusp in combination with venetoclax and azacitidine.

Treatment:

Drug: Tagraxofusp

Drug: Azacitidine

Drug: Venetoclax

Part 2 - Tagraxofusp (Selected Dose) and TP53 Wild Type

Experimental group

Description:

Participants (TP53 wild type) will receive tagraxofusp in combination with venetoclax and azacitidine.

Treatment:

Drug: Tagraxofusp

Drug: Azacitidine

Drug: Venetoclax

Part 2 - Tagraxofusp (Selected Dose) and TP53 Mutated

Experimental group

Description:

Participants (TP53 mutated) will receive tagraxofusp in combination with venetoclax and azacitidine.

Treatment:

Drug: Tagraxofusp

Drug: Azacitidine

Drug: Venetoclax