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

Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04977167
• Other study ID #: HG146CN102
• Status: Recruiting
• Phase: Phase 1
• Start date: July 28, 2023
• Est. completion date: December 2024

Study information

• Verified date: February 2024
• Source: HitGen Inc.
• Contact: Jie Shen
• Phone: 8628-85197385
• Email: jie.shen[@]hitgen.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 96
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Solid Tumor

Intervention

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

Locations

Country	Name	City	State
China	National Cancer Center/Cancer Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
HitGen Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Part 1:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)		Up to 2 years
Primary	Part1:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146		Up to 2 years
Primary	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
Primary	Part 2A:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)		Up to 2 years
Primary	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	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)
Secondary	Part 1:Peak plasma concentration (Cmax) 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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	OS		Up to 2 years