A Phase I, Multicenter, Open-label Study of TY-2136b, Administered Orally in Patients With Advanced or Metastatic Solid Tumors Harboring ALK, ROS1 or NTRK1-3 Alterations
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 282
- 试验地点
- 2
- 主要终点
- (Escalation stage) Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of TY-2136b and to determine the recommended phase 2 dose (RP2D), with dose-escalation stage and dose-expansion stage.
详细描述
- To evaluate the pharmacokinetic (PK) characteristics of TY-2136b after single and multiple oral doses.
- To assess preliminary antitumor activity of TY-2136b as a single agent when administered orally to patients with advanced or metastatic solid tumors.
- To identify mutations in the ALK, ROS1 and NTRK1-3, or other molecular alterations in blood or tumor tissues associated with clinical outcome.
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Escalation stage
Escalation stage: Multiple doses of TY-2136b for oral administration to find the maximum tolerated dose
干预措施: TY-2136b (Drug)
Expansion stage
Expansion stage: 4 distinct expansion cohorts
干预措施: TY-2136b (Drug)
结局指标
主要结局
(Escalation stage) Dose Limiting Toxicities (DLTs)
时间窗: Within 28 days of the first dose
Numbers of participants experiencing AEs which are defined as DLTs classfied by CTCAE v5.0.
(Escalation stage) Adverse events (AEs)
时间窗: From Baseline up to 28 days after the end of the treatment
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
(Escalation stage) Recommended Phase 2 Dose (RP2D)
时间窗: Within 28 days of the last patient dosed in escalation stage
The RP2D is defined as the dose level chosen for the dose expansion arms, based on safety, tolerability, efficacy, pharmacokinetics (PK), and pharmacodynamic (PD) data collected during the dose escalation portion of the study.
(Expansion stage) Overall Response Rate (ORR)
时间窗: From the date of first dose until the date of first documented progression or stable disease or the date of death from any cause, whichever came first, assessed up to 30 months.
ORR is defined as the percentage of subjects who have a partial response (PR) or complete response (CR) to the treatment response assessment in accordance to Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
次要结局
- (Escalation and Expansion stage) Maximum plasma concentration (Cmax)(Cycle 1 Day1 and Cycle 1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days))
- (Escalation and Expansion stage) Minimum plasma concentration (Cmin)(Cycle1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days))
- (Escalation and Expansion stage) Progression-free survival (PFS)(Up to 30 months after the date of first dose.)
- (Escalation and Expansion stage) Duration of Response (DOR)(Up to 30 months after the date of first dose.)
- (Escalation and Expansion stage) Area under the plasma concentration time curve(AUC0-t)(Cycle 1 Day 1 and Cycle 1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days))
- (Escalation and Expansion stage) Area under the plasma concentration time curve(AUC0-inf)(Cycle 1 Day 1 (at pre-dose, 0.5, 1, 2, 4, 6, 24 h post-dose) (Each Cycle=28 days))
- (Escalation and Expansion stage) Terminal half-life (t1/2)(Cycle1 Day 1 and Cycle1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days))
- (Escalation and Expansion stage) The time to the peak concentration (Tmax)(Cycle1 Day 1 and Cycle1 Day 21 (at pre-dose, 0.5,1, 2, 4, 6, 24 hours post-dose)(Each Cycle=28 days))
- (Escalation stage) Overall Response Rate (ORR)(From the date of first dose until the date of first documented progression or stable disease or the date of death from any cause, whichever came first, assessed up to 30 months.)
- (Escalation and Expansion stage) Overall survival (OS)(Up to 30 months after the date of first dose.)