GPC3-CAR-T Cells for the Hepatocellular Carcinoma

The Phase I Efficacy and Safety Clinical Study of GPC3-CAR-T Cells in Hepatocellular Carcinoma Patients

This is a single center, single arm, open-label, phase I study to evaluate the safety and efficacy of GPC3-CAR-T cells in patients with hepatocellular carcinoma.

Study Overview

• Status: Suspended
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Biological: GPC3-CAR-T cells

Detailed Description

GPC3-CAR-T cells is a novel CAR-T cells which designed for the cell membrane protein Glypican-3. Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells will be intravenously infused with a escalated dose of 1×106, 3×106, 10×106 GPC3-CAR-T cells. Tumor markers and GPC3-CAR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14, day 28). The aim of this clinical trial is to evaluate the safety and efficacy of GPC3-CAR-T cells therapy in patients with hepatocellular carcinoma. The primary endpoint is the safety of CAR-T cells including the effect ratio of CRS and ICANS, ORR. The secondary endpoint is the CAR-T ratio and CAR gene copied number in PB, PFS, OS and DOR.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Tsinghua Changgung Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age ≧18years, gender unlimited.
2. Failure or intolerance after at least first-line treatment.
3. GPC3 positive(IHC)
4. Patients must have at least one target lesion available for evaluation.
5. BCLC B or C.
6. Child-Pugh grade A or B
7. ECOG is 0 or 1 (one week before enrollment.)
8. Estimated life expectancy ≥ 3 months.
9. Functioning of major organs are normal.
10. Women of childbearing age (15-49 years old) must receive a pregnancy test within 7 days prior to initiation of treatment and the results are negative; male and female patients with fertility must use an effective contraceptive to ensure 3 months after discontinuation of treatment during the study period not pregnant inside.
11. Patients who voluntarily sign informed consent and are willing to comply with treatment plans, visit arrangements, laboratory tests and other research procedures.

Exclusion Criteria:

1. There are uncontrollable active infections that need systemic treatment.
2. HIV antibody is positive or syphilis antibody is positive.
3. Pregnant or lactating women.
4. hepatic encephalopathy.

5. patients with organ failure:

   • Heart: NYHA heart function grade IV;
   • Liver: Grade C that achieves Child-Turcotte liver function grading;
   • Kidney: kidney failure and uremia;
   • Lung: symptoms of respiratory failure;
   • Brain: a person with a disability.
6. It is undergoing systemic hormones therapy.
7. Impact results show that over 50% of the liver is occupied by tumor .
8. Patients who are still in the observation stage of other antitumor drugs 30 days before blood collection.
9. Patients were received other gene therapy products, or are participating in other clinical trials within 4 weeks prior to cell infusion.
10. Abnormal thyroid function ≧Level 3.
11. Active autoimmune diseases require systemic treatment during the first two years of screening.
12. Patients have mental illness or history of drug abuse.
13. Patients are participating in other clinical studies.
14. The researchers found that it was unsuitable for the recipients to be enrolled.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: GPC3-CAR-T cells; Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells will be intravenously infused with a escalated dose of 1×106 /3×106/10×106GPC3-CAR-T cells. Tumor markers and GPC3-CAR-T cell proliferation will be monitored in the scheduled time (day 0, day 4, day 7, day 10, day 14,day 21, day 28).	Biological: GPC3-CAR-T cells; Patients with hepatocellular carcinoma will be enrolled, and GPC3-CAR-T cells will be intravenously infused with a escalated dose of 1×106 /3×106/10×106GPC3-CAR-T cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of adverse events	Percentage of participants with adverse events.	12months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Remission Rate(ORR)	The percentage of participants who achieved complete remission (CR) and partial remission over all participants.	12months
Proliferation ratio of CAR-T cells		12months

Collaborators and Investigators

• Sponsor: Beijing Tsinghua Chang Gung Hospital
• Collaborators: China Immunotech (Beijing) Biotechnology Co., Ltd.
• Investigators: Study Director: Gong Li, M.A., Beijing Tsinghua Changgeng Hospital

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): June 10, 2022
• Primary Completion (ANTICIPATED): June 10, 2023
• Study Completion (ANTICIPATED): October 10, 2023

Study Registration Dates

• First Submitted: August 6, 2020
• First Submitted That Met QC Criteria: August 7, 2020
• First Posted (ACTUAL): August 10, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 29, 2022
• Last Verified: January 1, 2022

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: HXYT-009

Drug and device information, study documents

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