A First-In-Human, Phase 1, Dose Escalation Study of SGR-2921 as Monotherapy In Subjects With Relapsed/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 66
- 试验地点
- 12
- 主要终点
- Electrocardiograms in Singlicate and Triplicate
研究概览
简要总结
The purpose of this study is to evaluate safety and tolerability and to determine the maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-2921.
详细描述
This is a study of SGR-2921, an oral, small molecule inhibitor of cell division cycle 7-related protein kinase (CDC7), in subjects with Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS) to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), maximum tolerated dose (MTD) and/or recommended dose (RD) of SGR-2921.
Exploratory cohorts may evaluate additional PK, PD, preliminary anti-tumor activity, and safety to establish the SGR-2921 RD. A planned amendment will evaluate SGR-2921 in combination with other approved AML/MDS treatments such as hypomethylating agents (HMA), BCL2 inhibitors, IDH inhibitors or FLT3 inhibitors, in patients with AML and/or 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
- •≥ 18 years of age.
- •Life expectancy ≥ 8 weeks.
- •Confirmed diagnosis of R/R AML or High Risk (HR) and Very High Risk (VHR) MDS.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
排除标准
- •Active malignancies within two years prior to the first dose, or requiring ongoing treatment, not related to AML or MDS.
- •Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, ≥ Grade 3 disseminated intravascular coagulation, or active CNS leukemia.
- •Use of experimental drug, or therapy, or anti-cancer therapy within 14 days or 5 half-lives of the first dose of study drug.
- •QT interval corrected for heart rate per Fridericia's formula ≥470 msec during screening ECG.
研究组 & 干预措施
Dose Escalation in the Absence of Specific Azole Antifungal Treatments
Up to 9 dose levels will be evaluated in subjects not receiving specific azole antifungal treatment.
干预措施: SGR-2921 (Drug)
Dose Escalation in the Presence of Specific Azole Antifungal Treatments
Up to 9 dose levels will be evaluated in subjects receiving specific azole antifungal treatment.
干预措施: SGR-2921 (Drug)
结局指标
主要结局
Electrocardiograms in Singlicate and Triplicate
时间窗: Throughout the study, up to 26 months.
Uncorrected QT interval, QTcF, PR duration, QRS interval, and RR interval.
Dose Limiting Toxicities
时间窗: From first dose until the end of Cycle 1 (approximately 28 days, up to 42 days).
Adverse Events
时间窗: Throughout the study, up to 26 months.
Incidence, nature, and severity of adverse events (AEs) as assessed by the NCI CTCAE v5.0.
次要结局
- SGR-2921 Area Under the Concentration Versus Time Curve (AUC)(Throughout the study, up to 26 months.)
- SGR-2921 Minimum Plasma Concentration (Cmin)(Throughout the study, up to 26 months.)
- SGR-2921 Maximal Plasma Concentration (Cmax)(Throughout the study, up to 26 months.)
- Duration of Response (DOR) for Subjects with AML(Throughout the study, up to 26 months.)
- SGR-2921 Time to Maximal Plasma Concentration (tmax)(Throughout the study, up to 26 months.)
- Composite Complete Remission (CR) Rate for Subjects with AML(Throughout the study, up to 26 months.)
- Objective Response Rate (ORR) for Subjects with AML(Throughout the study, up to 26 months.)
- Objective Response Rate (ORR) for Subjects with MDS(Throughout the study, up to 26 months.)
- Duration of Response (DOR) for subjects with MDS(Throughout the study, up to 26 months.)