Clinical Trial of HG146 Administered to Subjects with Advanced Solid Tumors or Lymphoma
- Registration Number
- NCT04977167
- Lead Sponsor
- HitGen Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 96
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1:HG146 Monotherapy, Dose-escalation Cohort HG146 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. Part 2A:HG146 + PD-(L)1 antibody, Dose escalation Cohort HG146 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. Part 2A:HG146 + PD-(L)1 antibody, Dose escalation Cohort PD-(L)1 antibody 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. Part 2B-1：HG146 combination Expansion Cohort 1 HG146 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. Part 2B-1：HG146 combination Expansion Cohort 1 PD-(L)1 antibody 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. Part 2B-2：HG146 combination Expansion Cohort 2 HG146 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. Part 2B-2：HG146 combination Expansion Cohort 2 PD-(L)1 antibody 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.
- Primary Outcome Measures
Name Time Method Part 1:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) Up to 2 years Part1:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146 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) Up to 21 Days in Cycle 1 Part 2A:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE) Up to 2 years Part 2A:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146 in combination with PD-(L)1 antibody Up to 2 years 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) Up to 26 Days in Cycle 0 and Cycle 1
- Secondary Outcome Measures
Name Time Method 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) Plasma concentration of HG146 will be measured following single dose and multiple dose administration
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) Plasma concentration of HG146 will be measured following single dose and multiple dose administration
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) Plasma concentration of HG146 will be measured following single dose and multiple dose administration
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) Plasma concentration of HG146 will be measured following single dose and multiple dose administration
Part1: objective response rate (ORR) Up to 2 years ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part1: Best overall response (BOR) Up to 2 years BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part1: Duration of response (DOR) Up to 2 years DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part 1:Time-to-response (TTR) Up to 2 years TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part 1:Progression-Free Survival (PFS) Up to 2 years PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
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) Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Part 2:maximum observed plasma concentration (Cmax) of HG146 At the end of Cycle 1 Day 15 (each cycle is 21 days) Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Part 2:time of maximum observed plasma concentration (Tmax) of HG146 At the end of Cycle 1 Day 15 (each cycle is 21 days) Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Part2: objective response rate (ORR) Up to 2 years ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part2: Best overall response (BOR) Up to 2 years BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part2: Duration of response (DOR) Up to 2 years DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part 2:Time-to-response (TTR) Up to 2 years TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
Part 2:Progression-Free Survival (PFS) Up to 2 years PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)
OS Up to 2 years Part 2:apparent terminal half-life (T1/2) of HG146 At the end of Cycle 1 Day 15 (each cycle is 21 days) Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody
Trial Locations
- Locations (1)
National Cancer Center/Cancer Hospital
🇨🇳Beijing, China