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

Advanced Hepatocellular Carcinoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05352542
• Other study ID #: BM2L202005
• Status: Recruiting
• Phase: Phase 1
• Start date: May 19, 2022
• Est. completion date: October 2026

Study information

• Verified date: July 2023
• Source: The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
• Contact: Jianming Xu
• Phone: 13910866712
• Email: jianmingxu2014[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: October 2026
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Biological:
• LCAR-H93T Cells
before treatment with LCAR-H93T cells, subjects will receive a conditioning regimen

Locations

Country	Name	City	State
China	Beijing Gobroad Boren Hospital	Beijing	Beijing
China	Chinese PLA General Hospital	Beijing	Beijing
China	The First Affiliated Hospital of Xi 'an Jiaotong University School of Medicine	Xi'an	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
jianming xu	Nanjing Legend Biotech Co.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	Recommended Phase 2 dose (RP2D) finding	RP2D established through ATD+BOIN design	30 days after LCAR-H93T infusion (Day 1)
Primary	CAR positive T cells	CAR positive T cells after LCAR-H93T infusion	Minimum 2 years after LCAR-H93T infusion (Day 1)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)