GPC3-targeting LCAR-H93T Cell in Treatment of Advanced Hepatocellular Carcinoma
Study Details
Study Description
Brief Summary
A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting LCAR-H93T Cell in Treatment of Advanced Hepatocellular Carcinoma
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LCAR-H93T Cells Each subject will receive LCAR-H93T cells |
Biological: LCAR-H93T Cells
before treatment with LCAR-H93T cells, subjects will receive a conditioning regimen
|
Outcome Measures
Primary Outcome Measures
- Incidence, severity, and type of treatment-emergent adverse events (TEAEs) [Minimum 2 years after LCAR-H93T infusion (Day 1)]
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
- Dose-limiting toxicity (DLT) rate [Minimum 2 years after LCAR-H93T infusion (Day 1)]
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.
- Recommended Phase 2 dose (RP2D) finding [30 days after LCAR-H93T infusion (Day 1)]
RP2D established through ATD+BOIN design
- CAR positive T cells [Minimum 2 years after LCAR-H93T infusion (Day 1)]
CAR positive T cells after LCAR-H93T infusion
- CAR transgene levels in peripheral blood [Minimum 2 years after LCAR-H93T infusion (Day 1)]
CAR transgene levels in peripheral blood after LCAR-H93T infusion
Secondary Outcome Measures
- Overall response rate (ORR) [Minimum 2 years after LCAR-H93T infusion (Day 1)]
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
- Disease control rate (DCR) [Minimum 2 years after LCAR-H93T infusion (Day 1)]
Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial responses and stable disease
- Duration of Response(DoR) [Minimum 2 years after LCAR-H93T infusion (Day 1)]
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)
- Time to Response (TTR) [Minimum 2 years after LCAR-H93T infusion (Day 1)]
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
- Progress Free Survival (PFS) [2 years after LCAR-H93T infusion (Day 1)]
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
- Overall Survival (OS) [Minimum 2 years after LCAR-H93T infusion (Day 1)]
Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-H93T to death of the subject
- Incidence of anti-LCAR-H93T antibody [Minimum 2 years after LCAR-H93T infusion (Day 1)]
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
Eligibility Criteria
Criteria
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;
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Age 18-75 years;
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Patients diagnosed as advanced hepatocellular carcinoma (HCC) histopathologically or cytologically; Progression or intolerance after previous standard systemic therapy;
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GPC3 is detected positive by immunohistochemistry (IHC);
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Child-Pugh score ≤ 7;
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At least one assessable tumor lesion;
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ECOG score: 0-1;
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Expected survival ≥ 3 months;
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Clinical laboratory values meet screening visit criteria
Exclusion Criteria:
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Previous CAR-T cell, TCR-T cell or other cell therapies or therapeutic tumor vaccination directed at any target;
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Any previous GPC3 targeted therapy;
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Prior antitumor therapy with insufficient washout period;
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Brain metastases with central nervous system symptoms;
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Pregnant or lactating women
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HCV-Ab or/and HIV-Ab positive; active syphilis;
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Severe underlying diseases
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Any condition that, in the opinion of the investigator, will make the subject unsuitable for participation in this study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Beijing Gobroad Boren Hospital | Beijing | Beijing | China | |
| 2 | Chinese PLA General Hospital | Beijing | Beijing | China | |
| 3 | The First Affiliated Hospital of Xi 'an Jiaotong University School of Medicine | Xi'an | Shanxi | China |
Sponsors and Collaborators
- jianming xu
- Nanjing Legend Biotech Co.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BM2L202005