A Phase 1, Multicenter, Open Label Study of AMV564, a Bispecific CD33/CD3 T-cell Engager, in Patients With Intermediate or High-Risk Myelodysplastic Syndromes
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 5
- 主要终点
- Dose limiting toxicity (Dose Escalation)
研究概览
简要总结
An open label, Phase 1, study of AMV564 as monotherapy to assess the safety and efficacy in patients with Myelodysplastic Syndromes
详细描述
A dose-escalation with expansion study of AMV564 (T cell engager) as monotherapy in patients with intermediate-2 or high-risk Myelodysplastic Syndromes
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
- •≥ 18 years of age
- •Diagnosis of MDS according to WHO 2016 criteria
- •ECOG performance status of 0 or 1
- •Intermediate-2 or high-risk disease per IPSS
- •Fewer than 20% blasts in the bone marrow or peripheral blood
- •Disease that is refractory to or relapsed from either a hypomethylating agent (e.g. decitabine or azacitidine) or a standard AML-type intensive regimen
- •Adequate organ function
- •Prior allogeneic transplant performed ≥ 3 months prior to first dose of AMV564 is allowed provided there is no evidence of active graft-versus-host disease (GVHD) and the patient has been off immunosuppressive therapy for ≥ 4 weeks.
排除标准
- •History of, or known, central nervous system (CNS) disease involvement, or prior history of National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Grade ≥ 3 drug-related CNS toxicity
- •Prior allogeneic transplant if performed < 3 months prior to first dose of AMV564, if patient has active GVHD, or if patient has not been off immunosuppressive
- •Prior treatment with a therapeutic agent targeting CD33 (e.g. gemtuzumab ozogamicin, SGN-CD33A or AMG 330).
研究组 & 干预措施
Dose Escalation (3+3 design)
A 3 + 3 design, with dose-escalation of AMV564, up to a Maximum Tolerated Dose (MTD) level. AMV564 will be tested as a 14-Day CIV regimen (14-Day Continuous Intravenous Infusion Regimen).
干预措施: AMV564 14-Day CIV (Drug)
Dose Expansion
Following determination of the MTD of AMV564, the study will expand at the MTD or a dose level lower than the MTD to obtain initial estimates of response rates and additional information on safety.
干预措施: AMV564 14-Day CIV (Drug)
结局指标
主要结局
Dose limiting toxicity (Dose Escalation)
时间窗: DLTs will be evaluated through 28 days for the 14-Day Continuous Intravenous Infusion Infusion regimen, and 35 days for the Intermittent Intravenous Dosing regimen
Dose limiting toxicity to be measured by AEs and SAEs by dose level
Overall Response Rate (Dose Expansion)
时间窗: The treatment period will extend from initiation of AMV564 treatment until the Safety Follow Up visit (30 days after the end of infusion), or response assessment of the last induction cycle, whichever occurs later.
Overall response rate (ORR), defined as the proportion of patients who achieve a CR, marrow CR or PR by IWG criteria. Point estimates for ORR, along with the approximate lower 1-sided 90% confidence intervals, will be calculated.
次要结局
未报告次要终点