Phase I Multicenter, Open-Label, First-in-Human Study of BMS-986497 (ORM-6151) as a Monotherapy, in Double Combination With Azacitidine and in Triple Combination With Azacitidine and Venetoclax in Subjects With Relapsed or Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 105
- 试验地点
- 15
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, drug levels, drug efficacy and determine the recommended dose of BMS-986497 as a monotherapy, in double combination with Azacitidine and in triple combination with Azacitidine and Venetoclax in participants with relapsed or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Adults with primary or secondary relapsed and/or refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
- •Detectable levels of cluster of differentiation 33 (CD33) expression.
- •Failed alternative therapies with established benefit.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2 and adequate organ function.
排除标准
- •Acute Promyelocytic Leukemia.
- •Clinically active central nervous system leukemia.
- •Active malignant solid tumor.
- •Pregnant or breastfeeding.
- •Other protocol-defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Part 1: Dose Escalation BMS-986497 (Monotherapy)
干预措施: BMS-986497 (Drug)
Part 2, Cohort A: Dose Expansion BMS-986497 (Combination Therapy)
干预措施: BMS-986497 (Drug)
Part 2, Cohort A: Dose Expansion BMS-986497 (Combination Therapy)
干预措施: Azacitidine (Drug)
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)
干预措施: BMS-986497 (Drug)
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)
干预措施: Azacitidine (Drug)
Part 2, Cohort B: Dose Expansion BMS-986497 (Triple Combination Therapy)
干预措施: Venetoclax (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years
Determine the Recommended Phase 2 Dose (RP2D) of BMS-986497 as Monotherapy
时间窗: Up to 2 years
RP2D of BMS-986497 as Combination Therapy
时间窗: Up to 2 years
The combination therapy included BMS-986497 and Azacitidine
RP2D of BMS-986497 as Triple Combination Therapy
时间窗: Up to 2 years
The triple combination therapy included BMS-986497, Azacitidine and Venetoclax.
Incidence of dose-limiting toxicities (DLTs)
时间窗: Up to 21 days
次要结局
- Best overall response (BOR)(Up to 4 years)
- Complete remission (CR)(Up to 4 years)
- Time to reach Cmax (Tmax)(Up to 2 years)
- Area under the curve from time 0 to last quantifiable concentration (AUC0-last)(Up to 2 years)
- Complete remission with incomplete hematologic recovery (Cri)(Up to 4 years)
- Event-free survival (EFS)(Up to 4 years)
- Transition rate to allogeneic hematopoietic stem cell transplantation (HSCT)(Up to 4 years)
- Maximum concentration (Cmax)(Up to 2 years)
- Overall response rate (ORR)(Up to 4 years)
- Duration of response (DoR)(Up to 4 years)
- Complete remission with partial hematologic recovery (CRh) rate(Up to 4 years)
- Incidence of Anti-drug antibody (ADA) against BMS-986497(Up to 2 years)