A Phase 1, Randomized, Open-Label, Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors (SNDX-275-0141, MK3475-460/KEYNOTE-460)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Changes from baseline in laboratory results
研究概览
简要总结
The objectives of this study are to explore different dosing levels and schedules of entinostat in combination with pembrolizumab in patients with advanced solid tumors, in terms of safety, tolerability, pharmacokinetics (PK), impact on immune correlatives, and efficacy
详细描述
This is a Phase 1, open-label, single center, randomized study to assess the safety and tolerability of 3 different dose regimens of entinostat in combination with pembrolizumab in patients with advanced solid tumors who previously completed Study SNDX-275-0140 (NCT02897778). Up to 30 patients will be randomized in a 1:1:1 fashion to one of three arms. In the event that greater than or equal to 2 out of the first 6 patients randomized experience a dose-limiting toxicity, the next patient randomized to that Arm will receive treatment at a reduced starting dose as outlined in the protocol.
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
- 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
- •Completed Study SNDX-275-0140 (NCT02897778)
- •Any AE or toxicity experienced in Study SNDX-275-0140 (NCT02897778) is resolved to less than or equal to Grade 1
- •Continues to meet inclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study
排除标准
- •Completed Study SNDX-275-0140 (NCT02897778) more than 30 days prior to Cycle 1 Day 1 of this study
- •Continues to meet exclusion criteria for Study SNDX-275-0140 (NCT02897778) at the time of entry into this study
研究组 & 干预措施
ENT 1mg daily with pembro every 3 weeks
Entinostat daily in combination with pembrolizumab every three weeks
干预措施: Entinostat (Drug)
ENT 1mg daily with pembro every 3 weeks
Entinostat daily in combination with pembrolizumab every three weeks
干预措施: Pembrolizumab (Drug)
ENT 5mg weekly with pembro every 3 weeks
Entinostat once weekly in combination with pembrolizumab every three weeks
干预措施: Entinostat (Drug)
ENT 5mg weekly with pembro every 3 weeks
Entinostat once weekly in combination with pembrolizumab every three weeks
干预措施: Pembrolizumab (Drug)
ENT 10mg bi-weekly with pembro every 3 weeks
Entinostat once every other week in combination with pembrolizumab every three weeks
干预措施: Entinostat (Drug)
ENT 10mg bi-weekly with pembro every 3 weeks
Entinostat once every other week in combination with pembrolizumab every three weeks
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Changes from baseline in laboratory results
时间窗: Baseline through 90 day safety follow-up visit
Changes from baseline in vital signs
时间窗: Baseline through 90 day safety follow-up visit
Incidence of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events (AEs) resulting in the permanent discontinuation of study drug, and deaths occurring within the reporting period required for the study
时间窗: Each treatment cycle is 21 days. All events will be collected from informed consent through 90 days post-last dose or through 30 days after initiation of new anti-cancer therapy
Changes from baseline in ECG results
时间窗: Baseline through 90 day safety follow-up visit
次要结局
- AUC0-t (area under the curve to last observed concentration time) of entinostat when given in combination with pembrolizumab(Pre-dose through Cycle 3 Day 1)
- AUC0-inf (area under the curve extrapolated to infinity) of entinostat when given in combination with pembrolizumab(Pre-dose through Cycle 3 Day 1)
- Cmax (maximum plasma concentration) of entinostat when given in combination with pembrolizumab(Pre-dose through Cycle 3 Day 1)
- Tmax (time to maximum plasma concentration) of entinostat when given in combination with pembrolizumab(Pre-dose through Cycle 3 Day 1)
- Vd (clearance and volume of distribution) of entinostat when given in combination with pembrolizumab(Pre-dose through Cycle 3 Day 1)
- T1/2 (elimination half life) of entinostat when given in combination with pembrolizumab(Pre-dose through Cycle 3 Day 1)