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CompletedNCT03884751Updated Feb 24, 2022

Chimeric Antigen Receptor T Cells Targeting Glypican-3

A Phase 1 interventional study of CAR-GPC3 T Cells in Hepatocellular Carcinoma, sponsored by CARsgen Therapeutics Co., Ltd.. Completed at 6 sites in China. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2022-02-24.

Sponsored by CARsgen Therapeutics Co., Ltd. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
9
Allocation
Not applicable
Ages
18 Years to 70 Years
Sex
All
01

Study summary

A Phase I Clinical Study of Chimeric Antigen Receptor T Cells Targeting Glypican-3 (CAR-GPC3 T Cells) in Patients with Advanced Hepatocellular Carcinoma

Read the detailed description

This is a phase I open-label, single-arm, multicenter clinical trial designed to observe and evaluate the safety, cell metabolokinetics, and efficacy of CAR-GPC3 T cells infused intravenously at single escalating doses in patients with advanced hepatocellular carcinoma.

Primary objectives:

  • To evaluate the safety and tolerability of CAR-GPC3 T cells infused intravenously at escalating doses in patients with advanced hepatocellular carcinoma.

Secondary objectives:

  • To evaluate the metabolic kinetics of single infusion of CAR-GPC3 T cells
  • To evaluate the overall safety and tolerability of infusion of CAR-GPC3 T cells
  • To observe the efficacy of CAR-GPC3 T cells in the treatment of advanced hepatocellular carcinoma
02

Conditions studied

  • Hepatocellular Carcinoma

Keywords

  • Hepatocellular Carcinoma
  • CAR-T
03

In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 9 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

Browse Carcinoma studies →

Lead sponsor

CARsgen Therapeutics Co., Ltd. is the lead sponsor of 13 studies on the registry; 5 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Aged 18 to 70 years, male or female;
  2. Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology who are not suitable for surgery or local treatment (including ablation, intervention, and radiotherapy), have developed progressive disease or intolerability after standard systemic therapies (including but not limited to systemic chemotherapy, molecular targeted therapy) and have no effective treatment at the time of enrollment;
  3. According to RECIST 1.1, patients have at least one evaluable target lesion, defined as: the longest diameter of non-lymph node lesion ≥ 10 mm, or the shortest diameter of lymph node lesion ≥ 15 mm); hepatic lesions require arterial phase contrast enhancement;
  4. In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
  5. According to Barcelona Clinic Liver Cancer staging(BCLC), the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
  6. Expected survival is > 12 weeks;
  7. Cirrhosis status Child-Pugh score: Grade A;
  8. Eastern Cooperative Oncology Group(ECOG) Performance Status score: 0 to 1 point;
  9. Without active hepatitis B and/or Hepatitis C;
  10. Have venous accesses for pheresis;
  11. Acceptable routine blood test showing no contraindication to the lymphodepletion pretreatment;
  12. Adequate liver, renal, cardiovascular, respiratory function;
  13. Subjects of childbearing age must undergo a serum pregnancy test within 14 days before the initiation of the study and the result must be negative. In addition, they should be willing to use a reliable method of contraception during the trial (within 24 months (M24) after cell infusion); male subjects whose spouses are women of childbearing age should undergo sterilization surgery or agree to use a reliable method of contraception during the trial;
  14. Understand and sign informed consent.

Exclusion criteria

Exclusion Criteria:

  1. Pregnant or breast-feeding women;
  2. HCV-RNA(Hepatitis C Virus RNA ), HIV antibodies or Syphilis Serological tests are positive;
  3. HBV(Hepatitis B) and HCV(Hepatitis C virus ) infection exist simultaneously;
  4. Any uncontrollable active infection
  5. Patients who had received systemic steroids or other immunosuppressive agents
  6. Previous or present hepatic encephalopathy;
  7. Current clinically significant ascites;
  8. ≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
  9. Metastases to the central nervous system and clinically significant central nervous system diseases;
  10. Patients with existing heart disease in need of treatment or hypertension that be poorly controlled
  11. Patients with known active autoimmune diseases which require to be treated with immunosuppressive agents including biological agents;
  12. Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
  13. Patients with local treatments such as surgical treatment, interventional therapy, radiotherapy, ablation or systemic chemotherapy were performed for the studied disease within 2 weeks prior to apheresis;Or received immunotherapy (PD-1/ PD-L1 monoclonal antibody, see Section 15) or any Chinese herbal or proprietary medicine for the control of liver cancer within 1 week prior to apheresis;Or received sorafenib, regofenib, ramvastinib and other tyrosine kinase inhibitor targeted drugs within 1 week prior to apheresis;Targeted therapy with anti-angiogenic monoclonal antibodies such as bevacizumab or its analogue 4 weeks prior to apheresis;
  14. Patiens with previous treatment with targeted GPC3, TCR-T or CAR-T;
  15. Patients who previously received anti-PD-1/ PD-L1 monoclonal antibody therapy within 4 weeks prior to apheresis;
  16. Patients who had uncured malignant tumors in the past 5 years or at the same time, excluding in situ cervical cancer and skin basal cell carcinoma;
  17. Other serious illnesses that may limit subjects to participate in the trial (such as poorly controlled diabetes mellitus, severe cardiac insufficiency , myocardial infarction or unstable arrhythmia or unstable angina pectoris within the last 6 months, lung embolism, chronic obstructive pulmonary diseases, interstitial pulmonary diseases,gastric ulcer, a history of gastrointestinal bleeding or a clear tendency to gastrointestinal bleeding;
  18. According to the investigators' evaluation, patients are unable or unwilling to comply with the requirements of the study protocol.
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
9 participants (actual)

Study arms

  • Experimental
    CAR-GPC3 T Cells

    The subjects are enrolled into 2 dose levels cohorts in sequence

    Biological: CAR-GPC3 T Cells

Interventions

  • BiologicalCAR-GPC3 T Cells

    CAR-GPC3 T Cells injection

    Also known as: Chimeric Antigen Receptor T Cells Targeting Glypican-3

06

What researchers measure

Primary outcomes

  1. Dose-limiting toxicity (DLT)

    Safety

    Time frame: After 28 days of single infusion

  2. Maximum tolerated dose (MTD)

    tolerability

    Time frame: After 28 days of single infusion

Secondary outcomes

  1. Pharmacokinetics (the copies of cells in vivo)

    Pharmacokinetics is the"Implantation endpoint" which is defined as the number of copies of CAR-GPC3 DNA in peripheral blood at each visit after infusion until any two consecutive test results are negative or below the detection limit. It aims to calculate the Peak Plasma Concentration (Cmax)

    Time frame: Day0~Week 26

  2. Pharmacokinetics ( the duration of survival of cells in vivo)

    Duration of CAR-GPC3 T cell persistence is the period from the day of infusion to the first negative test result or result lower than the detection limit.It aims to calculate the area under the plasma concentration versus time curve (AUC)

    Time frame: Day0~Week 26

  3. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Adverse events up to 24 months of follow-up visit judged by the investigator to be associated with CAR-GPC3T cell infusion, such as abnormalities or changes in laboratory examinations, physical examinations, vital signs, etc.

    Time frame: Month 24

  4. Antitumor efficacy-Progression-free survival (PFS)

    The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.

    Time frame: Month 24

  5. Antitumor efficacy-Duration of response (DOR)

    The period from the first evaluation of CR or PR to the first evaluation of PD(Progressive Disease) or death of any cause.

    Time frame: Month 24

  6. Antitumor efficacy-Duration of disease control (DDC)

    The period from the first evaluation of CR, PR, or SD to the first evaluation of PD or any cause of death.

    Time frame: Month 24

  7. Antitumor efficacy-Overall survival (OS)

    The period from the first infusion to any cause of death

    Time frame: Month 24

  8. Antitumor efficacy-Objective response rate (ORR);

    The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%). In the event of PR or CR, the subjects should confirm it no less than 4 weeks after the first evaluation

    Time frame: Month 24

  9. Antitumor efficacy-Disease control rate (DCR)

    The number of cases in which response (PR + CR) and stable disease (SD) are achieved from the start of cell infusion/the total number of evaluable cases (%).

    Time frame: Month 24

07

Study locations

6 sites
  • Nanfang Hospital of Southern Medical University
    Guangzhou, Guangdong 510000, China
  • The First Affiliated Hospital of Zhengzhou University
    Zhengzhou, Henan 450000, China
  • The 81st Hospital of Chinese PLA
    Nanjing, Jiangsu 210002, China
  • Renji Hospital Shang Hai Jiaotong Unversity of Medicine
    Shanghai, Shanghai 200001, China
  • Zhongshan Hospital of Fudan University
    Shanghai, Shanghai 200001, China
  • The First Affiliated Hospital Zhejiang University
    Hangzhou, Zhejiang 310006, China
08

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 24, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03884751
Lead sponsor
CARsgen Therapeutics Co., Ltd.
Collaborators
NanJing PLA 81 Hospital, First Affiliated Hospital of Zhejiang University, RenJi Hospital
Responsible party
Sponsor
First posted
Mar 21, 2019
Start date
Aug 15, 2019
Primary completion
May 28, 2021
Completion
Dec 3, 2021
Last update
Feb 24, 2022

Study contacts

Qin shukui, Pro
principal investigator · The 81st Hospital of PLA
Zhai bo, Pro
principal investigator · RenJi Hospital

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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