GPC3-targeting LCAR-H93T Cell in Treatment of Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting LCAR-H93T Cell in Treatment of Advanced Hepatocellular Carcinoma

Detailed Description
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This is an open-label, dose escalation/expansion study to assess the safety, tolerability, and efficacy of LCAR-H93T in patients ≥ 18 years of age with relapsed or refractory advanced hepatocellular carcinoma. Patients who meet the eligibility criteria will receive LCAR-H93T infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow up

Official Title
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A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting LCAR-H93T Cell in Treatment of Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Biological: LCAR-H93T Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent; Age 18-75 years; Patients diagnosed as advanced hepatocellular carcinoma (HCC) histopathologically or cytologically; Progression or intolerance after previous standard systemic therapy; GPC3 is detected positive by immunohistochemistry (IHC); Child-Pugh score ≤ 7; At least one assessable tumor lesion; ECOG score: 0-1; Expected survival ≥ 3 months; Clinical laboratory values meet screening visit criteria Exclusion Criteria: Previous CAR-T cell, TCR-T cell or other cell therapies or therapeutic tumor vaccination directed at any target; Any previous GPC3 targeted therapy; Prior antitumor therapy with insufficient washout period; Brain metastases with central nervous system symptoms; Pregnant or lactating women HCV-Ab or/and HIV-Ab positive; active syphilis; Severe underlying diseases Any condition that, in the opinion of the investigator, will make the subject unsuitable for participation in this study.

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: LCAR-H93T Cells<br>Each subject will receive LCAR-H93T cells | Biological: LCAR-H93T Cells<br>* before treatment with LCAR-H93T cells, subjects will receive a conditioning regimen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, severity, and type of treatment-emergent adverse events (TEAEs) | An adverse event refers to any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product (investigational or non-investigational), which does not necessarily have a causal relationship with the treatment | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| Dose-limiting toxicity (DLT) rate | Dose-limiting toxicity (DLT) refers to a drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose. | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| Recommended Phase 2 dose (RP2D) finding | RP2D established through ATD+BOIN design | 30 days after LCAR-H93T infusion (Day 1) | 
| CAR positive T cells | CAR positive T cells after LCAR-H93T infusion | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| CAR transgene levels in peripheral blood | CAR transgene levels in peripheral blood after LCAR-H93T infusion | Minimum 2 years after LCAR-H93T infusion (Day 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-H93T cell infusion, and the objective tumor response rate will be calculated for patients with measurable disease per RECIST 1.1 only | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| Disease control rate (DCR) | Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial responses and stable disease | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| Duration of Response(DoR) | Duration of Remission (DoR) is defined as the time from the first documentation of remission (PR or better) to the first documented disease progression evidence (according to RECIST 1.1) of the responders (who achieve PR or better response) | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| Time to Response (TTR) | Time to Response (TTR) is defined as the time from the date of first infusion of LCAR-H93T to the date of the first response evaluation of the subject who has met all criteria for PR or better | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| Progress Free Survival (PFS) | Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-H93T to the first documented disease progression (according to RECIST 1.1) or death (due to any cause), whichever occurs first | 2 years after LCAR-H93T infusion (Day 1) | 
| Overall Survival (OS) | Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-H93T to death of the subject | Minimum 2 years after LCAR-H93T infusion (Day 1) | 
| Incidence of anti-LCAR-H93T antibody | Venous blood samples will be collected to measure LCAR-H93T positive cell concentrations and the transgenic level of LCAR-H93T, at the time points when anti-LCAR-H93T antibody serum samples are evaluated | Minimum 2 years after LCAR-H93T infusion (Day 1) |