Phase 1 Study to Evaluate the Safety, PK, PD, and Clinical Activity of STC-15, a METTL-3 Inhibitor, in Subjects with Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 3
- 主要终点
- Number of participants with adverse events
研究概览
简要总结
This Phase 1, multi-center, open-label, first-in-human study evaluates multiple ascending daily oral doses of STC-15 in Q3W treatment cycles in a 3+3 cohort design with dose levels determined by a modified Fibonacci algorithm. The study is designed to systematically assess safety and tolerability, pharmacokinetics, pharmacodynamics and clinical activity of STC-15 in adult subjects with advanced malignancies. Dose levels for further evaluation in expansion cohorts will be selected based on all available PK, pharmacodynamic, target engagement, efficacy, safety, and tolerability data including long-term safety data beyond dose limiting toxicities (DLTs). The study may be amended to evaluate STC-15 in combination with a Food and Drug Administration-approved standard of care treatment regimen, which could encompass targeted/chemotherapy, radiation therapy and/or immunotherapy with immune checkpoint blockers.
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
- •Histologic or cytologic confirmation of advanced malignancy that has failed standard of care (SOC) therapy and no further SOC therapy is available or the subject has declined additional SOC therapy
- •Adequate organ and marrow function
- •ECOG PS of 0 or 1
排除标准
- •Treatment with any local or systemic antineoplastic therapy within 3 weeks prior to first dose of STC-15
- •Major surgery or radiation within the 3 weeks
- •Immune-related AEs from immunotherapy that required permanent discontinuation
- •Central nervous system (CNS) disease involvement, or prior history of Grade ≥3 drug-related CNS toxicity.
- •Active autoimmune disease that has required systemic treatment in the 2 years prior to Screening
研究组 & 干预措施
Dose Level 1
30mg capsules, daily administration for 3 week (21 day) cycles
干预措施: STC-15 (Drug)
Dose Level 2
30mg capsules, MWF administration for 3 week (21 day) cycles
干预措施: STC-15 (Drug)
Dose Level 3
100mg capsules, MWF administration for 3 week (21 day) cycles
干预措施: STC-15 (Drug)
Dose Level 4
30mg and 100mg capsules, M-MWF administration for 3 week (21 day) cycles
干预措施: STC-15 (Drug)
Dose Level 5
30mg and 100mg capsules, M-MWF administration for 3 week (21 day) cycles
干预措施: STC-15 (Drug)
结局指标
主要结局
Number of participants with adverse events
时间窗: Screening through end of treatment, approximately 6 months
To evaluate the incidence, severity, and duration of adverse events
Cmax (PK)
时间窗: Screening through Cycle 2 (each cycle is 21 days)
To determine the Cmax concentration over a dosing interval, systemic clearance, volume of distribution at steady-state (Vss), and accumulation ratio from first dose to steady-state.
Tmax (PK)
时间窗: Screening through Cycle 2 (each cycle is 21 days)
To determine the time to Cmax (Tmax)
Ctrough (PK)
时间窗: Screening through end of treatment, approximately 6 months
To determine observed trough serum concentration (Ctrough)
Terminal elimination half life (PK)
时间窗: Screening through Cycle 2 (each cycle is 21 days)
To determine the terminal elimination half-life (t½)
AUC (PK)
时间窗: Screening through Cycle 2 (each cycle is 21 days)
To determine AUC in 1 dosing interval
Average concentration (PK)
时间窗: Screening through Cycle 2 (each cycle is 21 days)
To determine the average concentration over a dosing interval
Systemic Clearance (PK)
时间窗: Screening through Cycle 2 (each cycle is 21 days)
To determine the systemic clearance
Volume of distribution at steady-state (PK)
时间窗: Screening through Cycle 2 (each cycle is 21 days)
To determine the volume of distribution at steady-state (Vss)
Accumulation ratio from first dose to steady-state (PK)
时间窗: Screening through end of treatment, approximately 6 months
To determine the accumulation ratio from first dose to steady-state
次要结局
- Efficacy as measured by RECIST 1.1 (DoR)(Screening through disease progression, approximately 6 months)
- Efficacy as measured by RECIST 1.1 (PFS)(Screening through disease progression, approximately 6 months)
- Efficacy as measured by RECIST 1.1 (DCR)(Screening through disease progression, approximately 6 months)
- Efficacy as measured by RECIST 1.1 (ORR)(Screening through disease progression, approximately 6 months)
- Recommended Phase 2 Dose (RP2D)(Screening through 90 days after the last dose of STC-15, approximately 9 months)