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

Primary Purpose

Advanced Hepatocellular Carcinoma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
LCAR-H93T Cells
Sponsored by
jianming xu
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. 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;
  2. Age 18-75 years;
  3. Patients diagnosed as advanced hepatocellular carcinoma (HCC) histopathologically or cytologically; Progression or intolerance after previous standard systemic therapy;
  4. GPC3 is detected positive by immunohistochemistry (IHC);
  5. Child-Pugh score ≤ 7;
  6. At least one assessable tumor lesion;
  7. ECOG score: 0-1;
  8. Expected survival ≥ 3 months;
  9. Clinical laboratory values meet screening visit criteria

Exclusion Criteria:

  1. Previous CAR-T cell, TCR-T cell or other cell therapies or therapeutic tumor vaccination directed at any target;
  2. Any previous GPC3 targeted therapy;
  3. Prior antitumor therapy with insufficient washout period;
  4. Brain metastases with central nervous system symptoms;
  5. Pregnant or lactating women
  6. HCV-Ab or/and HIV-Ab positive; active syphilis;
  7. Severe underlying diseases
  8. Any condition that, in the opinion of the investigator, will make the subject unsuitable for participation in this study.

Sites / Locations

  • Beijing Gobroad Boren HospitalRecruiting
  • Chinese PLA General HospitalRecruiting
  • The First Affiliated Hospital of Xi 'an Jiaotong University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LCAR-H93T Cells

Arm Description

Each subject will receive LCAR-H93T cells

Outcomes

Primary Outcome Measures

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
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.
Recommended Phase 2 dose (RP2D) finding
RP2D established through ATD+BOIN design
CAR positive T cells
CAR positive T cells after LCAR-H93T infusion
CAR transgene levels in peripheral blood
CAR transgene levels in peripheral blood after LCAR-H93T infusion

Secondary Outcome Measures

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
Disease control rate (DCR)
Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial responses and stable disease
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)
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
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
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
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

Full Information

First Posted
April 1, 2022
Last Updated
July 10, 2023
Sponsor
jianming xu
Collaborators
Nanjing Legend Biotech Co.
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1. Study Identification

Unique Protocol Identification Number
NCT05352542
Brief Title
GPC3-targeting LCAR-H93T Cell in Treatment of Advanced Hepatocellular Carcinoma
Official Title
A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting LCAR-H93T Cell in Treatment of Advanced Hepatocellular Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 19, 2022 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
October 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
jianming xu
Collaborators
Nanjing Legend Biotech Co.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
LCAR-H93T Cells
Arm Type
Experimental
Arm Description
Each subject will receive LCAR-H93T cells
Intervention Type
Biological
Intervention Name(s)
LCAR-H93T Cells
Intervention Description
before treatment with LCAR-H93T cells, subjects will receive a conditioning regimen
Primary Outcome Measure Information:
Title
Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
Description
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
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
Dose-limiting toxicity (DLT) rate
Description
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.
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
Recommended Phase 2 dose (RP2D) finding
Description
RP2D established through ATD+BOIN design
Time Frame
30 days after LCAR-H93T infusion (Day 1)
Title
CAR positive T cells
Description
CAR positive T cells after LCAR-H93T infusion
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
CAR transgene levels in peripheral blood
Description
CAR transgene levels in peripheral blood after LCAR-H93T infusion
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
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
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
Disease control rate (DCR)
Description
Disease Control Rate (DCR) is defined as the proportion of patients with complete response, partial responses and stable disease
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
Duration of Response(DoR)
Description
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 Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
Time to Response (TTR)
Description
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
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
Progress Free Survival (PFS)
Description
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
Time Frame
2 years after LCAR-H93T infusion (Day 1)
Title
Overall Survival (OS)
Description
Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-H93T to death of the subject
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)
Title
Incidence of anti-LCAR-H93T antibody
Description
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
Time Frame
Minimum 2 years after LCAR-H93T infusion (Day 1)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jianming Xu
Phone
13910866712
Email
jianmingxu2014@163.com
Facility Information:
Facility Name
Beijing Gobroad Boren Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fan Li
Phone
13126636699
Email
lifan30207@126.com
Facility Name
Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jianming Xu
Phone
13910866712
Email
jianmingxu2014@163.com
Facility Name
The First Affiliated Hospital of Xi 'an Jiaotong University School of Medicine
City
Xi'an
State/Province
Shanxi
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zheng Wu

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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