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Clinical Trial of HG146 Administered to Subjects With Advanced Solid Tumors or Lymphoma

Primary Purpose

Solid Tumor, Lymphoma

Status

Recruiting

Phase

Phase 1

Locations

China

Study Type

Interventional

Intervention

HG146

PD-(L)1 antibody

About this trial

This is an interventional treatment trial for Solid Tumor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

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.

Sites / Locations

National Cancer Center/Cancer HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Part 1:HG146 Monotherapy, Dose-escalation Cohort

Part 2A:HG146 + PD-(L)1 antibody, Dose escalation Cohort

Part 2B-1：HG146 combination Expansion Cohort 1

Part 2B-2：HG146 combination Expansion Cohort 2

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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)

Part 1:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)

Part1:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146

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)

Part 2A:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)

Part 2A:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146 in combination with PD-(L)1 antibody

Secondary Outcome Measures

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

Part 1:Peak plasma concentration (Cmax) of HG146

Plasma concentration of HG146 will be measured following single dose and multiple dose administration

Part 1:Time of Cmax (Tmax) of HG146

Plasma concentration of HG146 will be measured following single dose and multiple dose administration

Part 1:Apparent terminal half-life (T1/2) of HG146

Plasma concentration of HG146 will be measured following single dose and multiple dose administration

Part1: objective response rate (ORR)

ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part1: Best overall response (BOR)

BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part1: Duration of response (DOR)

DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part 1:Time-to-response (TTR)

TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part 1:Progression-Free Survival (PFS)

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

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

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

Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody

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

Part2: objective response rate (ORR)

ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part2: Best overall response (BOR)

BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part2: Duration of response (DOR)

DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part 2:Time-to-response (TTR)

TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Part 2:Progression-Free Survival (PFS)

PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Full Information

NCT ID

NCT04977167

First Posted

July 12, 2021

Last Updated

September 20, 2023

Sponsor

HitGen Inc.

1. Study Identification

Unique Protocol Identification Number

NCT04977167

Brief Title

Clinical Trial of HG146 Administered to Subjects With Advanced Solid Tumors or Lymphoma

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 28, 2023 (Actual)

Primary Completion Date

December 2023 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

HitGen Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Solid Tumor, Lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

96 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Part 1:HG146 Monotherapy, Dose-escalation Cohort

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2A:HG146 + PD-(L)1 antibody, Dose escalation Cohort

Arm Type

Experimental

Arm Description

Arm Title

Part 2B-1：HG146 combination Expansion Cohort 1

Arm Type

Experimental

Arm Description

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.

Arm Title

Part 2B-2：HG146 combination Expansion Cohort 2

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

HG146

Intervention Description

HG146 is available as Capsule at a unit dose strength of 5 mg and 10 mg.

Intervention Type

Drug

Intervention Name(s)

PD-(L)1 antibody

Intervention Description

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.

Primary Outcome Measure Information:

Title

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)

Time Frame

Up to 26 Days in Cycle 0 and Cycle 1

Title

Part 1:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)

Time Frame

Up to 2 years

Title

Part1:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146

Time Frame

Up to 2 years

Title

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)

Time Frame

Up to 21 Days in Cycle 1

Title

Part 2A:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)

Time Frame

Up to 2 years

Title

Part 2A:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146 in combination with PD-(L)1 antibody

Time Frame

Up to 2 years

Secondary Outcome Measure Information:

Title

Part 1:Area under the concentration versus time curve (AUC) of HG146

Description

Plasma concentration of HG146 will be measured following single dose and multiple dose administration

Time Frame

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)

Title

Part 1:Peak plasma concentration (Cmax) of HG146

Description

Plasma concentration of HG146 will be measured following single dose and multiple dose administration

Time Frame

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)

Title

Part 1:Time of Cmax (Tmax) of HG146

Description

Plasma concentration of HG146 will be measured following single dose and multiple dose administration

Time Frame

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)

Title

Part 1:Apparent terminal half-life (T1/2) of HG146

Description

Plasma concentration of HG146 will be measured following single dose and multiple dose administration

Time Frame

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)

Title

Part1: objective response rate (ORR)

Description

ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part1: Best overall response (BOR)

Description

BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part1: Duration of response (DOR)

Description

DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part 1:Time-to-response (TTR)

Description

TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part 1:Progression-Free Survival (PFS)

Description

PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part 2:Area under the concentration versus time curve (AUC) of HG146

Description

Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody

Time Frame

At the end of Cycle 1 Day 15 (each cycle is 21 days)

Title

Part 2:maximum observed plasma concentration (Cmax) of HG146

Description

Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody

Time Frame

At the end of Cycle 1 Day 15 (each cycle is 21 days)

Title

Part 2:time of maximum observed plasma concentration (Tmax) of HG146

Description

Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody

Time Frame

At the end of Cycle 1 Day 15 (each cycle is 21 days)

Title

Part 2:apparent terminal half-life (T1/2) of HG146

Description

Plasma concentration of HG146 will be measured following multiple dose administration in combination with PD-(L)1 antibody

Time Frame

At the end of Cycle 1 Day 15 (each cycle is 21 days)

Title

Part2: objective response rate (ORR)

Description

ORR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part2: Best overall response (BOR)

Description

BOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part2: Duration of response (DOR)

Description

DOR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part 2:Time-to-response (TTR)

Description

TTR will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Part 2:Progression-Free Survival (PFS)

Description

PFS will be assessed by the Investigators using RECIST v. 1.1 or Lugano 2014( If applicable)

Time Frame

Up to 2 years

Title

Time Frame

Up to 2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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）: 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Jie Shen

Phone

8628-85197385

Ext

8211

jie.shen@hitgen.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yuankai Shi

Organizational Affiliation

National Cancer Center/Cancer Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Cancer Center/Cancer Hospital

City

Beijing

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yuankai Shi

syuankaipumc@126.com

First Name & Middle Initial & Last Name & Degree

Yu mei Che

Phone

8628-85197385

Ext

8211

ym.che@hitgen.com

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Clinical Trial of HG146 Administered to Subjects With Advanced Solid Tumors or Lymphoma

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