A Study of QL1706H in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, Phase Ⅰ study of QL1706H in patients with advanced solid tumors. The study will evaluate the pharmacokenetics, safety, tolerability and preliminary efficacy of QL1706H.

Detailed Description
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The study is composed of 2 parts. Part 1 is a dose-escalation study to explore the pharmacokenetics (PK), safety, and tolerability of QL1706H. Part 2 of the study will explore the PK characteristics of differente intervals and sites of administration. All the PK parameters will determine the recommended Phase 2 dose (RP2D). The study was divided into screening/baseline, treatment and follow-up periods. Safety monitoring will be conducted throughout the study period.

Official Title
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A Phase Ⅰ Study to Evaluate the Pharmacokinetics, Safety, Tolerability and Efficacy of QL1706H in Advanced Solid Tumors

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: QL1706H


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects participate voluntarily and sign informed consent. Patients with Pathologically confirmed metastatic or recurrent malignant solid tumors, failure or intolerance of at least first-line treatment and unsuitable for radical treatment such as surgery Subject has at least one measurable lesion according to RECIST (V1.1) evaluation criteria. Eastern Cooperative Oncology Group (ECOG) score was 0 or 1. The extension of life is more than 3 months Vital organs' function is adequate for enrolling Subjects agree to use effective contraceptive measures.Women who have not been pregnant or breastfeeding. Before the first use of the investigational drug, all the reversible toxicity of the previous antitumor therapy returned to ≤1 (according to CTCAE V5.0),Excluding any grade of hair loss and pigmentation, grade 2 or less peripheral sensory neuropathy, and other abnormalities that the investigator and/or sponsor assessed to outweigh the risk of toxicity. Exclusion Criteria: Active autoimmune diseases that exist within 2 years prior to the first use of the investigational drug and require systemic treatment. There are known past grade 3 or 4 immune-related adverse events associated with antitumor immunotherapy. Symptomatic central nervous system (CNS) metastasis, pia metastasis or spinal cord compression due to metastasis prior to signing informed consent. Subjects with any of the following cardiovascular diseases that seriously endanger the safety of the subjects or affect the completion of the study Subjects with diseases that are planned to be treated with systemic corticosteroids or other immunosuppressive drugs during the study period Prior treatment with cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitor combined with programmed cell death protein-1 (PD-1) inhibitor, or CTLA-4 inhibitor combined with PD-L1 inhibitor. Had received chemotherapy, targeted therapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor treatments within 4 weeks before the first use of experimental drugs Subjects with positive antibodies to HIV;Treponema pallidum antibody positive;HBsAg positive patients with VIRAL DEoxy ribonucleic acid (HBV DNA) >2000 IU/ mL or 10^4 copy number/mL should receive antiviral therapy according to local treatment guidelines and be willing to receive antiviral therapy throughout the study period.Hepatitis C virus antibody positive and viral ribonucleic acid (HCV RNA) positive

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QL1706H<br>Part 1 (Dose escalation): QL1706H will be administered in sequential cohorts each receiving 1 dose of QL1706H by subcutaneous injection on day 1 and QL1706 by IV infusion on day 22, from then on will recieve QL1706 on day 1 of every 21-day cycle (3 weeks). Dose escalation will continue until the projected cohorts has been finished. Part 2 (Dose Exploration): The PK parameters of QL1706H will be tested at different administration intervals. | Drug: QL1706H<br>* QL1706H is the subcutaneousely administered formulation of QL1706, it contains two unique monoclonal antibodies.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minimum Serum Drug Concentration ( Ctrough) | The minimum serum drug concentration and area under serum concentration-time curve after single administration of QL1706H. | one cycle (3 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | Safety and tolerability, as defined by the rate of treatment-related adverse events as assessed by NCI CTCAE v5.0. | one cycle (3 weeks) |