Clinical trial NCT04977167: 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
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Lymphoma
Lead sponsor: HitGen Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-26
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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）:

  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.

Primary outcomes:
measure: 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)
timeFrame: Up to 26 Days in Cycle 0 and Cycle 1
measure: Part 1:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)
timeFrame: Up to 2 years
measure: Part1:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146
timeFrame: Up to 2 years
measure: 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)
timeFrame: Up to 21 Days in Cycle 1
measure: Part 2A:Number of participants experiencing Serious Adverse Events (SAEs) and Adverse Events (AE)
timeFrame: Up to 2 years
measure: Part 2A:Maximum tolerated dose or Recommended Phase Ib dose (RP2D) of HG146 in combination with PD-(L)1 antibody
timeFrame: Up to 2 years
Secondary outcomes:
measure: Part 1:Area under the concentration versus time curve (AUC) of HG146
timeFrame: 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)
measure: Part 1:Peak plasma concentration (Cmax) of HG146
timeFrame: 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)
measure: Part 1:Time of Cmax (Tmax) of HG146
timeFrame: 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)
measure: Part 1:Apparent terminal half-life (T1/2) of HG146
timeFrame: 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)
measure: Part1: objective response rate (ORR)
timeFrame: Up to 2 years
measure: Part1: Best overall response (BOR)
timeFrame: Up to 2 years
measure: Part1: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Part 1:Time-to-response (TTR)
timeFrame: Up to 2 years
measure: Part 1:Progression-Free Survival (PFS)
timeFrame: Up to 2 years
measure: Part 2:Area under the concentration versus time curve (AUC) of HG146
timeFrame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
measure: Part 2:maximum observed plasma concentration (Cmax) of HG146
timeFrame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
measure: Part 2:time of maximum observed plasma concentration (Tmax) of HG146
timeFrame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
measure: Part 2:apparent terminal half-life (T1/2) of HG146
timeFrame: At the end of Cycle 1 Day 15 (each cycle is 21 days)
measure: Part2: objective response rate (ORR)
timeFrame: Up to 2 years
measure: Part2: Best overall response (BOR)
timeFrame: Up to 2 years
measure: Part2: Duration of response (DOR)
timeFrame: Up to 2 years
measure: Part 2:Time-to-response (TTR)
timeFrame: Up to 2 years
measure: Part 2:Progression-Free Survival (PFS)
timeFrame: Up to 2 years
measure: OS
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: National Cancer Center/Cancer Hospital
Study officials:
affiliation: National Cancer Center/Cancer Hospital
name: Yuankai Shi
role: PRINCIPAL_INVESTIGATOR
References: