Lymphoma, Solid Tumor
Conditions
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.
Interventions
DRUGHG146
HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.
DRUGPD-(L)1 antibody
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.
Sponsors
HitGen Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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. * Ib dose expansion phase（Part 2）: 1. 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
1. Received prior therapies targeting HDAC. 2. Symptomatic central nervous system (CNS) metastases that have required steroids within 4 weeks prior to first dose of study treatment. 3. History of intolerant of anti-PD-(L)1 toxicity（Ib）. 4. A condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of enrollment. 5. Major surgery or major injury \<=28 days before the first dose of study treatment,or anticipated major surgery during the study. 6. Received other anticaner therapies within 4 weeks prior to first dose of study treatment or 5 half life period of anticancer drug . 7. Active infection requiring systemic treatment. 8. Prior allogeneic bone marrow transplantation or other solid organ transplantation ( Ib) 9. Active autoimmune disease or disease of impaired immune system(Ib). 10. History of Adrenal insufficiency.(Ib) 11. History orConcurrent condition of other malignant tumors. 12. 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. 13. History of severe lung disease. 14. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his/her compliance in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 |
| 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) |
Countries
China
Contacts
Primary ContactJie Shen
Outcome results
None listed