Clinical Trial of HG146 Administered to Subjects With Advanced Solid Tumors or Lymphoma
A Phase I Open Label Study of HG146 Alone /in Combination With PD-(L)1 Inhibitor Administered With and Without Anticancer Agents in Participants With Advanced Solid Tumors or Lymphoma
This is a Phase I, open-label, repeat-dose, non-randomized, multicenter study to evaluate the safety, tolerability, and preliminary clinical activity and establish a recommended dose of HG146 administered orally (PO) alone (Part 1) or co-administered (Part 2) with PD-（L）1 inhibitor in subjects with refractory/relapsed solid tumors or Lymphoma. Part 1 consists of a dose escalation phae,Part2 consists of a dose escalation phase and a cohort expansion phase. In Part 1, escalating doses of HG146 will be evaluated as guided by the "3+3" approach. In Part 2A, escalating doses of HG146 in combination with PD-(L)1 inhibitor will be evaluated as guided by the "3+3" approach. In Part 2B, subjects will receive a single dose level of HG146 as identified based on data from Part 2, in combination with PD-(L)1 inhibitor . A total of approximately 96 subjects will be enrolled in this study, approximately 36 for dose escalation cohorts, and approximately 60 in the expansion cohorts.
研究概览
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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Beijing、中国
- National Cancer Center/Cancer Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Key Inclusion Criteria:
1 Subject must be >=18 years of age at the time of signing the informed consent.
2- Ia/Ib dose escalation phase（Part1 and Part 2A）：Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established.
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Ib dose expansion phase（Part 2）:
- Cohort 1,Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established, have not been treated with PD-(L)1 antibody； 2）Cohort 2,Subjects with advanced/Metastatic solid tumors or Lymphoma, who have progressed on, be intolerant of, or ineligible for, all available therapies for which clinical benefit has been established, have progressed on PD-(L)1 antibody； 3 Measurable disease per RECIST version 1.1 or Lugano 2014（If applicable）. 4 Has Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1. 5 Has adequate organ function. 6 Signed informed consent form (ICF) and able to comply with study requirements.
Key Exclusion Criteria:
- Received prior therapies targeting HDAC.
- Symptomatic central nervous system (CNS) metastases that have required steroids within 4 weeks prior to first dose of study treatment.
- History of intolerant of anti-PD-(L)1 toxicity（Ib）.
- A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of enrollment.
- Major surgery or major injury <=28 days before the first dose of study treatment,or anticipated major surgery during the study.
- Received other anticaner therapies within 4 weeks prior to first dose of study treatment or 5 half life period of anticancer drug .
- Active infection requiring systemic treatment.
- Prior allogeneic bone marrow transplantation or other solid organ transplantation ( Ib)
- Active autoimmune disease or disease of impaired immune system(Ib).
- History of Adrenal insufficiency.(Ib)
- History orConcurrent condition of other malignant tumors.
- Recent (within the past 6 months) history of Unstable or serious diseases, such as pancreatitis, severe angina, prolonged QT interval, congestive heart failure, myocardial infarction, pulmonary hypertension, stroke, and severe seizures, etc.
- History of severe lung disease.
- Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：顺序分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Part 1:HG146 Monotherapy, Dose-escalation Cohort
Subjects will receive HG146 PO at every two days intervals (qod) for 14 consecutive days,7 days off, 21 days/ cycle. Escalating doses of HG146 will be evaluated using 3+3 approach. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
其他名称：
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实验性的：Part 2A:HG146 + PD-(L)1 antibody, Dose escalation Cohort
Subjects will receive HG146 PO at every two days intervals (qod) for 14 consecutive days,7 days off, along with PD-(L)1 antibody IV once every 3 weeks (Q3W),21 days/ cycle. Escalating doses of HG146 in combination with PD-(L)1 antibody will be evaluated. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
其他名称：
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
其他名称：
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实验性的：Part 2B-1：HG146 combination Expansion Cohort 1
Subjects who have not been treated with PD-(L)1 antibody，will receive HG146 po for 14 consecutive days,7 days off, in combination with PD-(L)1 antibody IV Q3W. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
其他名称：
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
其他名称：
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实验性的：Part 2B-2：HG146 combination Expansion Cohort 2
Subjects who have progressed on PD-(L)1 antibody, will receive HG146 po for 14 consecutive days,7 days off, in combination with PD-(L)1 antibody IV Q3W. |
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
其他名称：
PD-(L)1 Antibody is available as solution for infusion or lyophilized powder for reconstitution to be administered Q3W. It will be administered as an IV infusion for 30 minutes.
其他名称：
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Part I：Dose-Limiting Toxicities (DLTs)
大体时间：Up to 26 Days in Cycle 0 and Cycle 1
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Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) |
Up to 26 Days in Cycle 0 and Cycle 1
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Part I：Serious Adverse Events (SAEs) and Adverse Events (AE)
大体时间：Up to 2 years
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Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance. |
Up to 2 years
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Part I：Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146
大体时间：Up to 2 years
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Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results. |
Up to 2 years
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Part 2A: Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)
大体时间：Up to 21 Days in Cycle 1
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Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) |
Up to 21 Days in Cycle 1
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Part 2A: Serious Adverse Events (SAEs) and Adverse Events (AE)
大体时间：Up to 2 years
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Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) According to Safety performance. |
Up to 2 years
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Part 2A:Maximum tolerated dose or Recommended Phase II dose (RP2D) of HG146 in combination with PD-(L)1 antibody
大体时间：Up to 2 years
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Maximum tolerated dose or Recommended Phase II dose of HG146 will be decided according to safety and effective results. |
Up to 2 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Part 1:Area under the concentration versus time curve (AUC) of HG146
大体时间：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Part 1:Peak plasma concentration (Cmax) of HG146
大体时间：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Part 1:Time of Cmax (Tmax) of HG146
大体时间：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15(Except for cycle 0, each cycle is 21 days)
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Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15(Except for cycle 0, each cycle is 21 days)
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Part 1:Apparent terminal half-life (T1/2) of HG146
大体时间：At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Plasma concentration of HG146 will be measured following single dose and multiple dose administration |
At the end of Cycle 0 Day 5 (Cycle 0 is 5 days);At the end of Cycle 1 Day15 (Except for cycle 0, each cycle is 21 days)
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Part1: objective response rate (ORR)
大体时间：Up to 2 years
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ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part1: Best overall response (BOR)
大体时间：Up to 2 years
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BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part1: Duration of response (DOR)
大体时间：Up to 2 years
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DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part 1:Time-to-response (TTR)
大体时间：Up to 2 years
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TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part 1:Progression-Free Survival (PFS)
大体时间：Up to 2 years
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PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part 2:Area under the concentration versus time curve (AUC) of HG146
大体时间：At the end of Cycle 1 Day 15 (each cycle is 21 days)
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Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
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Part 2:maximum observed plasma concentration (Cmax) of HG146
大体时间：At the end of Cycle 1 Day 15 (each cycle is 21 days)
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Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
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Part 2:time of maximum observed plasma concentration (Tmax) of HG146
大体时间：At the end of Cycle 1 Day 15 (each cycle is 21 days)
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Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
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Part 2:apparent terminal half-life (T1/2) of HG146
大体时间：At the end of Cycle 1 Day 15 (each cycle is 21 days)
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Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody |
At the end of Cycle 1 Day 15 (each cycle is 21 days)
|
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Part2: objective response rate (ORR)
大体时间：Up to 2 years
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ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part2: Best overall response (BOR)
大体时间：Up to 2 years
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BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part2: Duration of response (DOR)
大体时间：Up to 2 years
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DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part 2:Time-to-response (TTR)
大体时间：Up to 2 years
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TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Part 2:Progression-Free Survival (PFS)
大体时间：Up to 2 years
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PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) |
Up to 2 years
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Overall survival (OS)
大体时间：Up to 2 years
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OS will be assessed by the investigators |
Up to 2 years
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合作者和调查者
赞助
调查人员
- 首席研究员：Yuankai Shi、National Cancer Center/Cancer Hospital
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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