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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1:HG146 Monotherapy, Dose-escalation Cohort | Experimental | 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 | Experimental | 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. |
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| Part 2B-1:HG146 combination Expansion Cohort 1 | Experimental | 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. |
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| Part 2B-2:HG146 combination Expansion Cohort 2 | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HG146 | Drug | HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg. |
|
| Measure | Description | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1:Area under the concentration versus time curve (AUC) of HG146 | 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) |
| Part 1:Peak plasma concentration (Cmax) of HG146 |
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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):
Key Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jie Shen | Contact | 8628-85197385 | 8211 | jie.shen@hitgen.com |
| Name | Affiliation | Role |
|---|---|---|
| Yuankai Shi | National Cancer Center/Cancer Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Center/Cancer Hospital | Recruiting | Beijing | China |
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| ID | Term |
|---|---|
| D008223 | Lymphoma |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
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| PD-(L)1 antibody | Drug | 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. |
|
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) |
| Part 1:Time of Cmax (Tmax) of HG146 | 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) |
| Part 1:Apparent terminal half-life (T1/2) of HG146 | 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) |
| Part1: objective response rate (ORR) | ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part1: Best overall response (BOR) | BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part1: Duration of response (DOR) | DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part 1:Time-to-response (TTR) | TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part 1:Progression-Free Survival (PFS) | PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part 2:Area under the concentration versus time curve (AUC) of HG146 | 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) |
| Part 2:maximum observed plasma concentration (Cmax) of HG146 | 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) |
| Part 2:time of maximum observed plasma concentration (Tmax) of HG146 | 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) |
| Part 2:apparent terminal half-life (T1/2) of HG146 | 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) |
| Part2: objective response rate (ORR) | ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part2: Best overall response (BOR) | BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part2: Duration of response (DOR) | DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part 2:Time-to-response (TTR) | TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| Part 2:Progression-Free Survival (PFS) | PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable) | Up to 2 years |
| OS | Up to 2 years |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |