A Phase I Clinical Study of HLX53 in Advanced/Metastatic Solid Tumors or Lymphoma

Study Overview
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Brief Summary
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This phase I, first-in-human, open-label clinical study will evaluate the safety, tolerability, kinetics and preliminary anti-tumor efficacy of intravenous infusion of HLX53 in patients with advanced or metastatic solid tumors or lymphoma for whom there is no standard therapy or no standard therapy available. HLX53 is an Fc fusion protein against TIGIT.

Detailed Description
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Accelerated titration and 3 + 3 dose escalation were used in this trial . Six dose groups were preset, including 50 mg，150 mg，400 mg，800 mg，1600 mg， 2400 mg by intravenous infusion.

Official Title
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A Phase I Clinical Study to Evaluate the Safety, Tolerability, Kinetic Characteristics and Preliminary Efficacy of HLX53 in Advanced/Metastatic Solid Tumors or Lymphoma

Conditions
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Advanced/Metastatic Solid Tumors or Lymphoma

Intervention / Treatment
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* Biological: HLX53


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntary participation in clinical studies, full understanding of the trial, and signing of informed consent, willingness to follow and ability to complete the study in accordance with the requirements of the trial protocol. histologically or cytologically confirmed advanced/metastatic solid tumors or lymphoma, failure of standard therapy, or no standard therapy. Age ≥ 18 years and ≤ 75 years at the time of informed consent. Eastern Cooperative Oncology Group (ECOG) score 0 or 1. At least one measurable lesion according to RECISTv1.1 or 2014 Lugano (lymphoma) response evaluation criteria. Life expectancy of more than three months. Adequate hematological function. Adequate liver function. Adequate renal function Adequate cardiac function. Male and female subjects of childbearing potential must agree to use at least 1 highly effective method of contraception during the trial and for at least 6 months after the last dose of study drug. Exclusion Criteria: Known history of serious allergy to the components of HLX53 or to any monoclonal antibody. Prior treatment with anti-TIGIT or antibody to the relevant target CD155, CD112, or CD113. Unresolved toxicity after prior antineoplastic therapy, i.e., not resolved to baseline, Grade 0-1 per NCI-CTCAE 5.0 (except alopecia). Coexisting unstable or controlled medical conditions. Spinal cord compression with clinical symptoms. Prior allogeneic bone marrow transplant or solid organ transplant. History of primary immunodeficiency. History of eczema or asthma that cannot be controlled by topical corticosteroids. History of any second malignancy within 2 years, except for curatively treated early malignancies (carcinoma in situ or stage I tumors) such as non-melanoma skin cancer, carcinoma in situ of the cervix, localized prostate cancer, ductal carcinoma in situ of the breast, papillary thyroid cancer. Vaccination with a live attenuated vaccine within 4 weeks prior to the first dos.e Use of immunosuppressive drugs within 2 weeks prior to initial administration. Received major surgery, anti-tumor therapy (chemotherapy, radiotherapy, targeted therapy, immunotherapy or biological therapy) within 4 weeks prior to the first dose. Known to have active infectious disease such as active HBV, HCV infection. History of human immunodeficiency virus (HIV) infection. Pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HLX53<br> | Biological: HLX53<br>* The 50 mg, 150 mg, 400 mg, and 800 mg dose groups were administered once every 1 week (QW); the 1600 mg dose group was administered once every 2 weeks (Q2W); and the 2400 mg dose group was administered once every 3 weeks (Q3W).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse event | Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 for patients receiving study drug. | Through study completion, assessed up to 2 years. | 
| Incidence of DLT | Ratio of the number of patients with DLT events in each dose group to the number of patients in the dose group during the DLT evaluation period. | Up to 4 weeks. | 
| MTD | The maximum tolerated dose (MTD) of HLX53 | Up to 4 weeks | 
| RP2D | The recommended phase II dose (RP2D) of HLX53 | Through study completion, assessed up to 2 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Peak concentration of HLX53 | From baseline to 30 days after the last administration, assessed up to 7 months | 
| Tmax | Time to reach peak concentration of HLX53 | From baseline to 30 days after the last administration, assessed up to 7 months | 
| t1/2 | Elimination half-life of HLX53 | From baseline to 30 days after the last administration, assessed up to 7 months | 
| TIGIT Receptor Occupancy | TIGIT Receptor Occupancy of HLX53 on Peripheral Circulating T Cells | From baseline to 30 days after the last administration，assessed up to 7 months | 
| ADA | Incidence of anti-drug antibodies (ADA) | From baseline to 30 days after the last administration，assessed up to 7 months | 
| Objective response rate (ORR) | Percentage of patients with complete response or partial response determined by investigators according to RECIST v1.1, iRECIST 2017 (solid tumors), or Lugano 2014 (lymphoma). | Through study completion, assessed up to 2 years. | 
| Progression-free survival (PFS) | PFS is defined as the time from the first administration of HLX53 to the first occurrence of disease progression or death due to any cause, whichever occurs first. | From date of the first HLX53 administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years. | 
| Overall survival(OS) | OS is defined as the time from the first administration of HLX53 to death due to any cause. | From date of the first HLX53 administration until the date of death from any cause, whichever came first, assessed up to 2 years. |