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

Phase 1RecruitingNCT04977167

HitGen Inc.96 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Solid Tumor Lymphoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

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

Time frame: Up to 2 years

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

Time frame: 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)

Time frame: Up to 21 Days in Cycle 1

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

Time frame: Up to 2 years

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 Outcomes

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

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)

Part 1:Peak plasma concentration (Cmax) of HG146

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)

Part 1:Time of Cmax (Tmax) of HG146

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)

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

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)

Part1: objective response rate (ORR)

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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: Up to 2 years

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts