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

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

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 Overview

• Status: Recruiting
• Conditions: Advanced Hepatocellular Carcinoma
• Intervention / Treatment: Biological: LCAR-H93T Cells

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 Type: Interventional
• Enrollment (Estimated): 34
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jianming Xu; Phone Number: 13910866712; Email: jianmingxu2014@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Chinese PLA General Hospital
      • Contact: Jianming Xu; Phone Number: 13910866712; Email: jianmingxu2014@163.com
    • Beijing, Beijing, China
      • Recruiting
      • Beijing GoBroad Boren Hospital
      • Contact: Fan Li; Phone Number: 13126636699; Email: lifan30207@126.com
  • Shanxi
    • Xi'an, Shanxi, China
      • Not yet recruiting
      • The First Affiliated Hospital of Xi 'an Jiaotong University School of Medicine
      • Contact: Zheng Wu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

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: 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: jianming xu
• Collaborators: Nanjing Legend Biotech Co.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2022
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: April 1, 2022
• First Submitted That Met QC Criteria: April 23, 2022
• First Posted (Actual): April 29, 2022

Study Record Updates

• Last Update Posted (Actual): July 11, 2023
• Last Update Submitted That Met QC Criteria: July 10, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: BM2L202005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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