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

HitGen

Status and phase: Enrolling; Phase 1

Conditions: Solid Tumor; Lymphoma

Treatments: Drug: HG146; Drug: PD-(L)1 antibody

Study type: Interventional

Funder types: Industry

Identifiers

NCT04977167

HG146CN102

Details and patient eligibility

About

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.

Enrollment: 96 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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96 participants in 4 patient groups

Part 1:HG146 Monotherapy, Dose-escalation Cohort

Experimental group

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.

Treatment:

Drug: HG146

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

Experimental group

Description:

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.

Treatment:

Drug: PD-(L)1 antibody

Drug: HG146

Part 2B-1：HG146 combination Expansion Cohort 1

Experimental group

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.

Treatment:

Drug: PD-(L)1 antibody

Drug: HG146

Part 2B-2：HG146 combination Expansion Cohort 2

Experimental group

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.

Treatment:

Drug: PD-(L)1 antibody

Drug: HG146