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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- HitGen Inc.
- 入组人数
- 96
- 试验地点
- 1
- 主要终点
- Part 1:Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)
研究概览
简要总结
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
- •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.
- •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 ≤
- •5 Has adequate organ function. 6 Signed informed consent form (ICF) and able to comply with study requirements.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: HG146 (Drug)
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.
干预措施: HG146 (Drug)
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.
干预措施: PD-(L)1 antibody (Drug)
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.
干预措施: HG146 (Drug)
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.
干预措施: PD-(L)1 antibody (Drug)
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.
干预措施: HG146 (Drug)
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.
干预措施: PD-(L)1 antibody (Drug)
结局指标
主要结局
Part 1:Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)
时间窗: Up to 26 Days in Cycle 0 and Cycle 1
Part 1:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)
时间窗: Up to 2 years
Part1:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146
时间窗: Up to 2 years
Part 2A:Number of participants experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v.5.0)
时间窗: Up to 21 Days in Cycle 1
Part 2A:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)
时间窗: Up to 2 years
Part 2A:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146 in combination with PD-(L)1 antibody
时间窗: Up to 2 years
次要结局
- Part 2:apparent terminal half-life (T1/2) of HG146(At the end of Cycle 1 Day 15 (each cycle is 21 days))
- Part 1:Area under the concentration versus time curve (AUC) of HG146(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))
- Part 1:Peak plasma concentration (Cmax) of HG146(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))
- Part 1:Time of Cmax (Tmax) of HG146(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))
- Part 1:Apparent terminal half-life (T1/2) of HG146(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))
- Part1: objective response rate (ORR)(Up to 2 years)
- Part1: Best overall response (BOR)(Up to 2 years)
- Part1: Duration of response (DOR)(Up to 2 years)
- Part 1:Time-to-response (TTR)(Up to 2 years)
- Part 1:Progression-Free Survival (PFS)(Up to 2 years)
- Part 2:Area under the concentration versus time curve (AUC) of HG146(At the end of Cycle 1 Day 15 (each cycle is 21 days))
- Part 2:maximum observed plasma concentration (Cmax) of HG146(At the end of Cycle 1 Day 15 (each cycle is 21 days))
- Part 2:time of maximum observed plasma concentration (Tmax) of HG146(At the end of Cycle 1 Day 15 (each cycle is 21 days))
- Part2: objective response rate (ORR)(Up to 2 years)
- Part2: Best overall response (BOR)(Up to 2 years)
- Part2: Duration of response (DOR)(Up to 2 years)
- Part 2:Time-to-response (TTR)(Up to 2 years)
- Part 2:Progression-Free Survival (PFS)(Up to 2 years)
- OS(Up to 2 years)