A Phase I, Open-Label, Multicenter, Dose Escalation and Expansion Study of HM16390, as a Single Agent and in Combination With Pembrolizumab, in Patients With 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
- 292
- 试验地点
- 7
- 主要终点
- Incidence and nature of DLTs
研究概览
简要总结
This is a First-in-Human, Phase 1, Dose-Escalation and Dose-Expansion study of HM16390, as a single agent and in combination with pembrolizumab to assess safety, tolerability, MTD, RP2D, PK, and efficacy in patients with advanced or metastatic solid tumors.
Dose-Escalation Part is planned to establish the MTD or RDs for the randomized Dose-Ranging Part. Based on the results of the Dose-Escalation Part, additional eligible subjects will be randomized 1:1 into each dose level. After a comprehensive review of available data from both Dose-Escalation Part and Dose-Ranging Part, the RDEs to be tested in the Dose-Expansion Part are determined. Dose-Expansion Part is designed to assess the potential efficacy of HM16390 as a single agent and in combination with pembrolizumab when administered at the RDEs to subjects in indication-specific expansion cohorts.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Have a histologically and/or cytologically confirmed advanced or metastatic solid tumor and have failed or are intolerant to standard therapy with clinical benefit.
- •Patients in the Dose-Escalation Part must have evaluable or measurable disease at baseline and the patients for Dose-Ranging and Dose-Expansion Part must have at least one measurable lesion at baseline by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before allocation or randomization.
- •Age of 18 years or older (or country's legal age of majority if the legal age was >18 years)
- •Adequate renal function.
- •Adequate hematologic function.
- •Adequate liver function.
排除标准
- •Received prior treatment with agent targeting the IL-2, IL-7, or IL-15 receptors, or related to mode of action of HM
- •Known active CNS metastases and/or carcinomatous meningitis.
- •History of severe toxicities associated with a prior immunotherapy.
- •Any prior treatment-related (i.e. chemotherapy, immunotherapy, radiotherapy) clinically significant toxicities that have not resolved to Grade ≤ 1 per NCI-CTCAE version 5.0 or prior treatment-related toxicities that are clinically unstable and clinically significant at time of enrollment.
- •Has ongoing or suspected autoimmune disease.
- •Known active and clinically significant bacterial, fungal or viral infection including known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, immunocompromised patients.
- •History of chronic liver disease or evidence of hepatic cirrhosis.
研究组 & 干预措施
HM16390
HM16390 Monotherapy
干预措施: HM16390 (Drug)
HM16390 + pembrolizumab
HM16390 in combination with pembrolizumab
干预措施: HM16390 (Drug)
HM16390 + pembrolizumab
HM16390 in combination with pembrolizumab
干预措施: pembrolizumab (Drug)
结局指标
主要结局
Incidence and nature of DLTs
时间窗: At the end of Cycle 1 (each cycle is 21 days) in Dose-Escalation Part
To evaluate safety and tolerability of HM16390 as a single agent and in combination with pembrolizumab
Incidence, nature, and severity of adverse events and laboratory abnormalities graded per NCI-CTCAE v5.0.
时间窗: Throughout the study until end of safety follow-up period (90 days after the last treatment)
To evaluate safety and tolerability of HM16390 as a single agent, and in combination with pembrolizumab
次要结局
- The maximum serum concentration (Cmax)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The AUC extrapolated to infinity (AUCinf)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The AUC during the dosing interval (AUCtau)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The serum concentration at the end of the dosing interval (Ctrough)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The apparent volume of distribution (Vd/F)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The apparent clearance (CL/F)(Throughout the study until treatment discontinuation (up to 2-3 years))
- Disease Control Rate (DCR)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))
- Progression-free survival (PFS)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))
- The time to reach Cmax (Tmax)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The area under the concentration-time curve from time 0 to the last observable concentration (AUClast)(Throughout the study until treatment discontinuation (up to 2-3 years))
- The elimination half-life (T1/2)(Throughout the study until treatment discontinuation (up to 2-3 years))
- Objective response rate (ORR)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))
- Duration of response (DOR)(Throughout the study until disease progression or death whichever occurs first (up to 2-3 years))