A Study of Evorpacept (ALX148) With Venetoclax and Azacitidine for Acute Myeloid Leukemia (ASPEN-05)

Study Overview
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Brief Summary
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This Phase 1/2 clinical study will evaluate evorpacept (ALX148) in combination with venetoclax and azacitidine for the treatment of patients with acute myeloid leukemia (AML).

Detailed Description
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The Phase 1 will consist of a dose escalation of evorpacept (ALX148) in combination with venetoclax and azacitidine to evaluate safety and tolerability, and to identify the recommended Phase 2 dose of evorpacept (ALX148) in combination with venetoclax and azacitidine. The Phase 2 will evaluate the efficacy of evorpacept (ALX148) in combination with venetoclax and azacitidine for patients with AML.

Official Title
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A Phase 1/2 Study of Evorpacept (ALX148) in Combination With Venetoclax and Azacitidine in Patients With Acute Myeloid Leukemia (AML) (ASPEN-05)

Conditions
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Acute Myeloid Leukemia, AML, Adult

Intervention / Treatment
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* Drug: evorpacept
* Drug: venetoclax
* Drug: azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cytologically or histologically confirmed diagnosis of relapsed/refractory or newly diagnosed AML per WHO 2016 classification. Phase 1a: AML that is relapsed/refractory or that is previously untreated in patients not considered suitable for intensive induction therapy. Phase 1b: AML that is relapsed/refractory after prior treatment with a HMA-based regimen. Phase 2: Previously untreated AML in patients who are not considered suitable candidates for intensive induction therapy. Adequate renal and liver function. Age ≥18 years. Adequate performance status. Exclusion Criteria: In Phase 1a and 1b, patients that have undergone prior allo-HSCT must be at least 3 months post-HSCT, without uncontrolled graft-versus-host disease (GVHD). For Phase 2, patients that have undergone prior allo-HSCT are excluded. Patients with newly diagnosed AML with favorable risk cytogenetics such as t(8;21), inv(16), or t(16;16) as per the NCCN Guidelines Version 3, 2019 for AML. Patients with acute promyelocytic leukemia (APL). Prior treatment with any anti-CD47 or anti-SIRPalpha (signal regulatory protein alpha) agent. Known active viral infections, including hepatitis B and C, human immunodeficiency virus (HIV), acquired immunodeficiency syndrome (AIDS) related illness, or SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: evorpacept (ALX148) + venetoclax + azacitidine<br>Phase 1a: Participants will receive escalating doses of evorpacept (ALX148) in combination with venetoclax and azacitidine Phase 1b/2: Participants will receive evorpacept (ALX148) at the recommended Phase 2 dose in combination with venetoclax and azacitidine | Drug: evorpacept<br>* Fusion protein that blocks CD47-SIRPalpha pathway<br>* Other names: ALX148;Drug: venetoclax<br>* BCL-2 inhibitor<br>* Other names: Venclexta;Drug: azacitidine<br>* Hypomethylating agent (HMA)<br>* Other names: Vidaza;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Dose Limiting Toxicities (DLT) | Number of participants with a DLT | Up to 28 days | 
| Phase 2: Composite complete remission rate (CRc) | Number of participants achieving a complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) per European LeukemiaNet (ELN) 2017 criteria | Approximately 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALX148, CD47, SIRPalpha, azacitidine, venetoclax, evorpacept