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

Study of GPC-3 CAR-T Cells in Advanced Hepatocellular Carcinoma

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.

Study Overview

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

Detailed Description

Hepatocellular carcinoma is a highly heterogeneous disease. Treatment strategies for advanced hepatocellular carcinoma are limited. Resulting in a poor prognosis. 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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Li Yu, Dr; Phone Number: +8675521839178; Email: liyu@vip.163.com

Study Locations

• China
  • Guangdong
    • Shenzhen, Guangdong, China, 518000
      • Recruiting
      • Li Yu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 40~70 years old;
2. 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;
3. Patients who have been terminated for more than 28 days due to previous ineffective PD-1 monoclonal antibody treatment;
4. 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;
5. Tumor tissue samples were positive for GPC3 by immunohistochemistry (IHC);
6. Grade C according to Barcelona liver cancer grading standard (BCLC) or Grade B which is not suitable for local treatment/progression of local treatment;
7. Estimated survival time > 12 weeks;
8. Cirrhotic state Child Pugh score Grade A
9. ECOG physical status score 0~1;
10. 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);
11. Single vein access;
12. Blood routine test: WBC ≥ 2.5 × 109/L， PLT≥60 × 109/L， Hb≥9.0 g/dL，LY≥0.4 × 109/L；
13. 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;
14. 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
15. Be able to understand and sign the informed consent form

HBsAg positive patients must receive antiviral treatment according to the Guidelines for the Prevention and Treatment of Chronic Hepatitis B (2015);

11. Single vein access;

12. Blood routine test: WBC ≥ 2.5 × 109/L， PLT≥60 × 109/L， Hb≥9.0 g/dL，LY≥0.4 × 109/L；

13. 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;

14. 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

15. Be able to understand and sign the informed consent form

Exclusion Criteria:

1. Pregnant or lactating women;
2. HCV-RNA, HIV antibody or syphilis antibody are positive;
3. Any uncontrollable active infection, including but not limited to active tuberculosis;
4. Have received systemic steroids equivalent to>15 mg prednisone within 2 weeks before single collection, except inhaled steroids;
5. Allergies to immunotherapy and related drugs, previous severe allergies β- Allergy to lactam antibiotics;
6. Previous or current hepatic encephalopathy;
7. 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);
8. 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;
9. Central nervous system metastasis and diseases of central nervous system with clinical significance;
10. 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);
11. Patients with known active autoimmune diseases need to be treated with immunosuppressants including biological agents;
12. Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
13. 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;
14. Received targeted GPC3 treatment, TCR-T treatment and CAR-T treatment in the past month;
15. Being treated with anti PD-1/PD-L1 monoclonal antibody in the past 28 days;
16. Other incurable malignant tumors in the past 5 years or at the same time, excluding cervical carcinoma in situ and skin basal cell carcinoma;
17. Other serious diseases that may restrict the subjects from participating in this trial (such as diabetes under poor control (HbA1c>7% after treatment), severe cardiac insufficiency (LVEF<45%), myocardial infarction or unstable arrhythmia or unstable angina pectoris in the last 6 months, pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease Pulmonary function test FEV1 accounts for less than 60% of the estimated value, gastric ulcer, history of gastrointestinal bleeding disease or clear gastrointestinal bleeding tendency);
18. The investigator assessed that the patient was unable or unwilling to comply with the requirements of the study protocol.

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: Treatment group; GCP3 CAR-T cells	Biological: GPC3 CAR-T cells; patients treated with GPC3 CAR-T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE/SAE	adverse event/sever adverse event	from cell infusion to 30 days after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	overall response rate	From admission to the end of follow up, up to 2 years.

Collaborators and Investigators

• Sponsor: Shenzhen University General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2022
• Primary Completion (Anticipated): October 31, 2025
• Study Completion (Anticipated): October 31, 2028

Study Registration Dates

• First Submitted: November 11, 2022
• First Submitted That Met QC Criteria: November 11, 2022
• First Posted (Actual): November 17, 2022

Study Record Updates

• Last Update Posted (Actual): November 22, 2022
• Last Update Submitted That Met QC Criteria: November 17, 2022
• Last Verified: November 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: HEM-ONCO-023

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