Phase 1/2 Open Label Dose-escalation and Expansion Trial of NKT2152 an Orally Administered HIF2α Inhibitor to Investigate Safety Pharmacokinetics Pharmacodynamics and Clinical Activity in Patients With Advanced Clear Cell Renal Cell Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 120
- 试验地点
- 13
- 主要终点
- Objective Response Rate (ORR) determined by the Investigator in the Dose Expansion Phase (Phase 2)
研究概览
简要总结
The goal of the Phase 1 portion is to identify the maximum tolerated dose (MTD) and/or the recommended doses for expansion (RDEs) of NKT2152. The Phase 2 portion will evaluate the efficacy of NKT2152 in ccRCC.
详细描述
This is a Phase 1/2 open label multicenter study of NKT2152. Phase 1 is a first in human (FIH) dose escalation study in patients aged 18 years or older with clear cell renal carcinoma (ccRCC) who have exhausted available standard therapy as determined by the investigator.
Phase 1 is designed to determine the MTD and/or RDEs of NKT2152 as a single agent administered orally once daily. Depending on the tolerability and PK, additional dosing schedules may be tested. Phase 2 will evaluate the safety, pharmacokinetics and antitumor efficacy of NKT2152 in ccRCC patients. Patients will be randomized to one of two dosage levels selected for further evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
Phase 1 dose escalation
Phase 1 is designed to determine the maximum tolerated dose and/or identify the recommended Phase 2 dose of NKT2152 as a single agent administered orally once daily in ccRCC patients
干预措施: Oral NKT2152 (Drug)
Phase 2 dose expansion
Phase 2 dose expansion will evaluate the safety, pharmacokinetics and antitumor efficacy of NKT2152 as a single agent administered orally once daily in ccRCC patients. Patients will be randomized to one of two dosage levels being evaluated.
干预措施: Oral NKT2152 (Drug)
结局指标
主要结局
Objective Response Rate (ORR) determined by the Investigator in the Dose Expansion Phase (Phase 2)
时间窗: Approximately 1 year
ORR defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Recommended Doses for Expansion (RDEs) Determined in the Dose Escalation Phase (Phase 1)
时间窗: Approximately 2 years
The RDE(s) will be determined based on observed dose-limiting toxicities (DLTs) and using the totality of (AUC0-∞) and biological data in Phase 1.
Recommended Phase 2 Dose (RP2D)
时间窗: Approximately 1 year
Further assess RDEs to determine the RP2D for NKT2152.
Number of Participants with Dose Limiting Toxicity (DLT) events during the DLT monitoring period (first 21 days of dosing) in the Dose Escalation Phase (Phase 1)
时间窗: 21 days
DLTs graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5 .0.
次要结局
- Area under the plasma concentration time curve (AUC0-t) of NKT2152(Up to Day 22)
- Objective Response Rate (ORR) determined by the Investigator in the Dose Escalation Phase (Phase 1)(Approximately 1 year)
- Overall survival (OS)(Through study completion, an average of 2 years)
- Progression free survival (PFS)(Through study completion, an average of 2 years)
- Number of Participants with Adverse Events(Approximately 2 years)
- Maximum observed plasma concentration (Cmax) of NKT2152(Up to Day 22)
- Time to maximum observed plasma concentration of NKT2152 (Tmax)(Up to Day 22)
- Area under the plasma concentration time curve (AUC0-∞) of NKT2152(Up to Day 22)
- Duration of response (DOR)(Approximately 1 year)
- Disease control rate (DCR) determined by the Investigator(Approximately 1 year)