ENHANCE: A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination With Azacitidine Versus Azacitidine Plus Placebo in Treatment-naïve Patients With Higher Risk Myelodysplastic Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 539
- 试验地点
- 169
- 主要终点
- Percentage of Participants With Complete Remission (CR)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Magrolimab + Azacitidine
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.
干预措施: Magrolimab (Drug)
Magrolimab + Azacitidine
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.
干预措施: Azacitidine (Drug)
Control Arm (Placebo + Azacitidine)
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.
干预措施: Azacitidine (Drug)
Control Arm (Placebo + Azacitidine)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Complete Remission (CR)
时间窗: From randomization up to 31.01 months
The percentage of participants (CR rate) are participants who reach morphologic CR (morphological blast of ≤ 5% and recovery of absolute neutrophil count (ANC), platelets, and hemoglobin from complete blood counts as well as peripheral blast) based on Investigator-assessed International Working Group (IWG) myelodysplastic syndrome (MDS) criteria on or prior to initiation of any new anticancer therapy, including stem cell therapy (SCT). Percentages were rounded off.
Overall Survival (OS)
时间窗: From randomization up to 32.62 months
OS is defined as the number of months measured from the date of randomization to the date of death from any cause. Kaplan Meier (KM) estimates were used for analysis.
次要结局
- Duration of CR (DOCR)(From randomization up to 31.01 months)
- Duration of Response (DOR)(From randomization up to 31.01 months)
- Percentage of Participants With CR in Participants With TP53 Mutation(From randomization up to 31.01 months)
- Minimal Residual Disease (MRD)-Negative Response Rate(From randomization up to 31.01 months)
- Time to Transformation to AML(From randomization up to 31.01 months)
- Functional Assessment of Cancer Therapy-Anemia (FACT-Anemia) Response Rate(Up to week 136)
- Objective Response Rate (ORR)(From randomization up to 31.01 months)
- Red Blood Cell (RBC) Transfusion Independence Rate(From randomization up to 31.01 months)
- Event Free Survival (EFS)(From randomization up to 31.01 months)
- Progression Free Survival (PFS)(From randomization up to 31.01 months)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)(First dose date up to 135.9 weeks plus 70 days (Up to 2.8 years))
- Serum Concentration of Magrolimab(Preinfusion on Days 0, 7, 28, 56, 112, 168, 252 and 336)
- Percentage of Participants With Positive Anti-magrolimab Antibodies(Up to 72 hours before administration of any treatment at Day 1, Cycle 1; within 24 hours prior to any study drug administration at Day 1 of Cycles 2, 3, 5, 7, 10, and 13 and End of Treatment (± 7 Days after last study drug dose); Cycle length is 28 Days)