Study of GPC-3 CAR-T Cells in Treating With Hepatocellular Carcinoma

NCT05620706 | Recruiting

• 1 other identifier: HEM-ONCO-023
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma is a highly heterogeneous disease. Treatment strategies for advanced hepatocellular carcinoma are limited. Phosphatidylinositol proteoglycan 3 (GPC3) is a heparan sulfate glycoprotein (HSPG) on the surface of the cell membrane. It is highly expressed in liver cancer tissues, but hardly expressed in normal liver tissues. It is an ideal target for tumor treatment. Investigators aimed to test the safety and efficacy of GPC3 CAR-T cells in patients with advanced hepatocellular carcinoma.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• AE/SAE

  adverse event/sever adverse event

  from cell infusion to 30 days after infusion

Secondary Outcomes (1)

• ORR

  From admission to the end of follow up, up to 2 years.

Study Arms (1)

Treatment group

EXPERIMENTAL

GCP3 CAR-T cells

Biological: GPC3 CAR-T cells

Interventions

GPC3 CAR-T cells BIOLOGICAL

patients treated with GPC3 CAR-T cells

Treatment group

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \~70 years old;
• Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology, who are not suitable for surgery or local treatment (including ablation therapy, interventional therapy and radiotherapy), and who have experienced progress or intolerance after receiving standard treatment in the past;
• Patients who have been terminated for more than 28 days due to previous ineffective PD-1 monoclonal antibody treatment;
• At least one target lesion that can be evaluated stably according to RECIST 1.1 standard is defined as: the longest diameter of non lymph node lesions ≥ 10mm, or the short diameter of lymph node lesions ≥ 15mm; Intrahepatic lesions require enhanced imaging in arterial phase;
• Tumor tissue samples were positive for GPC3 by immunohistochemistry (IHC);
• Grade C according to Barcelona liver cancer grading standard (BCLC) or Grade B which is not suitable for local treatment/progression of local treatment;
• Estimated survival time \> 12 weeks;
• Cirrhotic state Child Pugh score Grade A
• ECOG physical status score 0\~1;
• If the patient is HBsAg positive or HBcAb positive, HBV-DNA\<200IU/ml. HBsAg positive patients must receive antiviral treatment according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2015);
• Single vein access;
• Blood routine test: WBC ≥ 2.5 × 109/L， PLT≥60 × 109/L， Hb≥9.0 g/dL，LY≥0.4 × 109/L；
• Blood biochemistry: serum Alb ≥ 30 g/L, serum lipase and amylase ≤ 1.5 ULN, serum creatinine ≤ 1.5 ULN and endogenous creatinine clearance rate ≥ 40mL/min, ALT ≤ 5ULN, AST ≤ 5ULN, total bilirubin ≤ 2.5ULN, prothrombin time extension ≤ 4s;
• The women of childbearing age must carry out serum pregnancy test within the screening period and 14 days before starting the study medication, and the result is negative. They are willing to use reliable methods of contraception during the test period (within 12 months (M12) after cell infusion); For male subjects whose partners are women of childbearing age, they should have undergone sterilization or agree to use reliable methods of contraception during the trial
• Be able to understand and sign the informed consent form

You may not qualify if:

• Pregnant or lactating women;
• HCV-RNA, HIV antibody or syphilis antibody are positive;
• Any uncontrollable active infection, including but not limited to active tuberculosis;
• Have received systemic steroids equivalent to\>15 mg prednisone within 2 weeks before single collection, except inhaled steroids;
• Allergies to immunotherapy and related drugs, previous severe allergies β- Allergy to lactam antibiotics;
• Previous or current hepatic encephalopathy;
• At present, there is ascites with clinical significance, which is defined as: ascites with positive signs on physical examination or ascites that need to be controlled by intervention (such as puncture or drug therapy) (only those with ascites shown on imaging without intervention can be included);
• Imaging examination results: the proportion of liver being replaced by tumor ≥ 50%, or portal trunk tumor thrombus, or tumor thrombus invading mesenteric vein/inferior vena cava;
• Central nervous system metastasis and diseases of central nervous system with clinical significance;
• At present, there is a heart disease that needs treatment or hypertension that is judged by the researcher to be poorly controlled (systolic blood pressure\>160mmHg or diastolic blood pressure\>100mmHg);
• Patients with known active autoimmune diseases need to be treated with immunosuppressants including biological agents;
• Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
• Have received treatment for the study disease within 2 weeks before single collection, including but not limited to surgical treatment, interventional treatment, radiotherapy, chemotherapy and immunotherapy;
• Received targeted GPC3 treatment, TCR-T treatment and CAR-T treatment in the past month;
• Being treated with anti PD-1/PD-L1 monoclonal antibody in the past 28 days;

Sponsors & Collaborators

• Shenzhen University General Hospital: lead

Study Sites (1)

Li Yu

Shenzhen, Guangdong, 518000, China

RECRUITING

Study Officials

• Li Yu, Dr

  Shenzhen University General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Yu, Dr

CONTACT

+8675521839178; liyu@vip.163.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 11, 2022
• First Posted: November 17, 2022
• Study Start: November 1, 2022
• Primary Completion: October 31, 2025
• Study Completion (Estimated): October 31, 2028
• Last Updated: November 22, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)