Magrolimab + Azacitidine Versus Azacitidine + Placebo in Untreated Participants With Myelodysplastic Syndrome (MDS) (ENHANCE)

Gilead Sciences

Status and phase: Terminated; Phase 3

Conditions: Myelodysplastic Syndromes

Treatments: Drug: Placebo; Drug: Azacitidine; Drug: Magrolimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04313881

2020-004287-26 (EudraCT Number)

5F9009

Details and patient eligibility

About

The primary objective of this study is to evaluate the efficacy of magrolimab in combination with azacitidine compared to that of azacitidine plus placebo in previously untreated participants with intermediate/high/very high risk myelodysplastic syndrome (MDS) by Revised International Prognostic Scoring System (IPSS-R) as measured by complete remission (CR) and overall survival (OS).

Enrollment: 539 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Participants with Myelodysplastic Syndrome (MDS) defined according to World Health Organization classification, with Revised International Prognostic Scoring System (IPSS-R) prognostic risk category of intermediate, high, or very high risk.
• Adequate performance status and hematological, liver, and kidney function.

Key Exclusion Criteria:

• Immediate eligibility for allogenic stem cell transplant (SCT), as determined by the investigator, with an available donor.
• Prior treatment with Cluster of Differentiation (CD) 47 or Signal-regulatory protein alpha (SIRPα)-targeting agents.
• Any prior antileukemic therapy for treatment of intermediate, high, very high risk MDS per IPSS-R.
• Second malignancy, except treated basal cell or localized squamous skin carcinomas, localized prostate cancer, or other malignancies for which participants are not on active anticancer therapies and have had no evidence of active malignancy for at least ≥ 1 year.
• Contraindications to azacitidine.
• Clinical suspicion of active central nervous system (CNS) involvement by MDS.
• Known active or chronic hepatitis B or C infection or human immunodeficiency virus in medical history .
• Active hepatitis B virus and/or active hepatitis C virus, and/or HIV following testing at screening.
• Pregnancy or active breastfeeding.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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539 participants in 2 patient groups, including a placebo group

Magrolimab + Azacitidine

Experimental group

Description:

Participants will receive the following magrolimab and azacitidine dosing regimens: Magrolimab: Magrolimab Priming Dose: * 1 mg/kg on Days 1 and 4 * 15 mg/kg on Day 8 * 30 mg/kg on Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50) Magrolimab Maintenance Dose: * 30 mg/kg on Day 57 and 30 mg/kg every 2 weeks thereafter. Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each 28-day cycle.

Treatment:

Drug: Azacitidine

Drug: Magrolimab

Control Arm (Placebo + Azacitidine)

Placebo Comparator group

Description:

Participants will receive the following placebo dosing regimens to mirror magrolimab dosing regimen in addition to azacitidine: Placebo: On Days 1 and 4; Day 8; Days 11, 15, followed by weekly administration for 5 doses (on Days 22, 29, 36, 43, and 50). Additionally, placebo was administered on Day 57 and every 2 weeks thereafter. Azacitidine: 75 mg/m\^2 on Days 1 to 7 (or Days 1 to 5 and 8 to 9) of each cycle.

Treatment:

Drug: Azacitidine

Drug: Placebo