A Multicenter, Open-label, Phase 1 Dose Escalation and Expansion Study of TXN10128, an Inhibitor of ENPP1 as Monotherapy and Combination Therapy With Irinotecan or Paclitaxel in Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 96
- 试验地点
- 6
- 主要终点
- Adverse events (AE)
研究概览
简要总结
This is a phase I clinical trial to primarily evaluate the safety, tolerability, and addtionally assess pharmacokinetics, pharmacodynamics, and antitumor activity of investigational product, TXN10128. The target subjects will be consisted of patients with locally advanced (unresectable) or metastatic soild tumors.
This study includes a dose-escalation part and a dose-expansion part, and a TXN10128 monotherapy part and a TXN10128 + Irinotecan or Paclitaxel combination therapy part.
详细描述
This study includes a dose-escalation part and a dose-expansion part, and a TXN10128 monotherapy part and a TXN10128 + Irinotecan or Paclitaxel combination therapy part. The study includes dose-escalation and dose-expansion parts across three cohorts: TXN10128 monotherapy (Cohorts A) TXN10128 + Irinotecan (Cohorts B) and TXN10128+ Paclitaxel (Cohorts C).
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects ≥19 years of age at the time of informed consent.
- •Histologically and/or cytologically confirmed any progressive, locally advanced (unresectable), or metastatic solid tumors that have relapsed or are refractory following the last line of treatment and for which prior standard therapy has been ineffective, or standard therapy does not exist or is not considered appropriate.
- •ECOG performance status of 0 or
- •Life expectancy of at least 12 weeks.
排除标准
- •Has leptomeningeal disease.
- •Experienced a Grade ≥3 immune-related adverse events (irAE) with prior immunotherapy with the exception of non-clinically significant laboratory abnormalities.
- •Prior organ transplantation.
- •Known positive human immunodeficiency virus (HIV) infection.
研究组 & 干预措施
Cohort A-1
TXN10128 Monotherapy Dose esclation part
干预措施: TXN10128 (Drug)
Cohort B-1
Combination Therapy with TXN10128 and Irinotecan Dose esclation part
干预措施: TXN10128 (Drug)
Cohort B-1
Combination Therapy with TXN10128 and Irinotecan Dose esclation part
干预措施: Irinotecan (Drug)
Cohort C-1
Combination therapy with TXN10128 and Paclitaxel Dose esclation part
干预措施: TXN10128 (Drug)
Cohort C-1
Combination therapy with TXN10128 and Paclitaxel Dose esclation part
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Adverse events (AE)
时间窗: Up to 30 days from end of treatment
Adverse events (AE) defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0 at each dose level
DLT
时间窗: Day 1 up to Day 21 for Cohort A(TXN10128 mono cohort) and Day 1 up to Day 28 for Cohort B,C(TXN10128 combination with Irinotecan or paclitaxel cohort) in dose escalation period
A DLT is defined as any of the following AEs (graded using NCI CTCAE v5.0) whose relationship to TXN10128 cannot be ruled out.
次要结局
- Cmax(Up to 21 days from Day 1 dose)
- AUC inf(Up to 21 days from Day 1 dose)
- AUC last(Up to 21 days from Day 1 dose)
- Tmax(Up to 21 days from Day 1 dose)
- Progression free survival (PFS)(Up to 30 days from end of treatment)
- Disease control rate (DCR)(Up to 30 days from end of treatment)
- Duration of Response (DOR)(Up to 30 days from end of treatment)
- Overall response rate (ORR)(Up to 30 days from end of treatment)
- T1/2(Up to 21 days from Day 1 dose)
- Vss(Up to 21 days from Day 1 dose)
- Best overall response (BOR)(Up to 30 days from end of treatment)