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

NCT ID: NCT04977167

Last Updated: 2024-10-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-28
• Study Completion Date: 2024-12-31

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.

Conditions

Solid Tumor; Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

HG146

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

HG146

Intervention Type: DRUG

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

PD-(L)1 antibody

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

HG146

Intervention Type: DRUG

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

PD-(L)1 antibody

Intervention Type: 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.

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.

Group Type: EXPERIMENTAL

HG146

Intervention Type: DRUG

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

PD-(L)1 antibody

Intervention Type: 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.

Interventions

HG146

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

Intervention Type: DRUG

PD-(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.

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HitGen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yuankai Shi

Role: PRINCIPAL_INVESTIGATOR

National Cancer Center/Cancer Hospital

Locations

National Cancer Center/Cancer Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Jie Shen

Role: CONTACT

jie.shen@hitgen.com

8628-85197385 ext. 8211

Facility Contacts

Yuankai Shi

Role: primary

syuankaipumc@126.com

Yu mei Che

Role: backup

ym.che@hitgen.com

8628-85197385 ext. 8211

Other Identifiers

HG146CN102

Identifier Type: -

Identifier Source: org_study_id