A Study of Evorpacept (ALX148) With Azacitidine for Higher Risk Myelodysplastic Syndrome (ASPEN-02)

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 azacitidine for the treatment of patients with higher risk myelodysplastic syndrome (MDS).

Detailed Description
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The Phase 1 will consist of a dose escalation of evorpacept (ALX148) in combination with azacitidine to evaluate safety and tolerability, and to identify the recommended Phase 2 dose of ALX148 in combination with azacitidine. The Phase 2 will evaluate the efficacy of evorpacept (ALX148) in combination with azacitidine compared to azacitidine alone for patients with previously untreated higher risk MDS.

Official Title
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A Phase 1/2 Study of Evorpacept (ALX148) in Combination With Azacitidine in Patients With Higher Risk Myelodysplastic Syndrome (MDS) (ASPEN-02)

Conditions
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Higher Risk Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: evorpacept
* Drug: azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase 1: Diagnosis of higher risk MDS that is either previously untreated or relapsed/refractory. Phase 2: Diagnosis of higher risk MDS that is previously untreated. Adequate renal and liver function. Age ≥18 years. Adequate performance status. Exclusion Criteria: Previous allogeneic hematopoietic stem cell transplant (allo-HSCT) for MDS or AML. Prior treatment with any anti-CD47 or anti-SIRPα (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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: evorpacept (ALX148) + azacitidine<br>Phase 1: Participants will receive escalating doses of evorpacept (ALX148) in combination with azacitidine 75 mg/m2 IV or subcutaneous daily for 7 days of a 28 day cycle Phase 2: Participants will receive evorpacept (ALX148) at the recommended Phase 2 dose in combination with azacitidine 75 mg/m2 IV or subcutaneous daily for 7 days of a 28-day cycle | Drug: evorpacept<br>* Fusion protein that blocks CD47-SIRPalpha pathway<br>* Other names: ALX148;Drug: azacitidine<br>* Hypomethylating agent (HMA)<br>* Other names: Vidaza;|
| Active Comparator: azacitidine<br>Phase 2 only: Participants will receive azacitidine 75 mg/m2 IV or subcutaneous daily for 7 days of a 28-day cycle | 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: Complete response rate (CRR) | Number of participants achieving a complete response per International Working Group (IWG) criteria | Approximately 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MDS, ALX148, CD47, Azacitidine, HMA, SIRP-alpha, evorpacept, High risk