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

A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetic Characteristics and Preliminary Efficacy of HLX53 (an Anti-TIGIT Fc Fusion Protein) in Patients With Advanced/Metastatic Solid Tumors

This phase I, first-in-human, open-label clinical study will evaluate the safety, tolerability, pharmacokinetic characteristics and preliminary efficacy of HLX53 (an anti-TIGIT Fc fusion protein) in patients with advanced/metastatic solid tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced/Metastatic Solid Tumors
• Intervention / Treatment: Biological: HLX53

Detailed Description

This study is an open-label phase I clinical study to evaluate the safety, tolerability , PK/PD and preliminary efficacy of HLX53 in patients with advanced/metastatic solid tumor. 11-30 subjects with advanced or metastatic solid tumors will be enrolled. The accelerated titration and traditional 3 + 3 dose escalation design will be implemented. Subjects will receive intravenous infusion of HLX53 at different doses according to the order of enrollment. There are 5 preset dose groups, namely 30mg/QW, 150mg/QW, 400mg/QW, 1000mg/Q3W and 2000mg/Q3W, administered by intravenous infusion. Observation period of DLT will last for 21 days after the first administration of HLX53. Maximum tolerated dose (MTD) definition: The highest dose level at which no more than 1 of 6 DLT-evaluable subjects developed DLT. At the MTD dose, at least 6 subjects were evaluable for DLT. When the MTD is determined, the MTD is usually used as the RP2D, or the RP2D is determined based on safety, PK/PD/ADA/NAb characteristics, and potential clinical efficacy.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HLX53; an anti-TIGIT Fc fusion protein	Biological: HLX53; There are 5 preset dose groups, namely 30mg/QW, 150mg/QW, 400mg/QW, 1000mg/Q3W and 2000mg/Q3W, administered by intravenous infusion.

What is the study measuring?

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 3 weeks.
RP2D	The recommended phase II dose (RP2D) of HLX53	Through study completion, assessed up to 2 years.
MTD	The maximum tolerated dose (MTD) of HLX53	Up to 3 weeks

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.

Collaborators and Investigators

• Sponsor: Shanghai Henlius Biotech
• Investigators: Principal Investigator: Jian Zhang, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2022
• Primary Completion (Estimated): December 4, 2024
• Study Completion (Estimated): March 4, 2025

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms
• Other Study ID Numbers: HLX53-FIH101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No