Hepatocellular Carcinoma
Conditions
Interventions
Group A:GPC3-CART-2*10^6
Group B:GPC3-CART-5*10^6
Group C:GPC3-CART-1*10^7
Sponsors
Zhongshan Hospital, Fudan University
Eligibility
Sex/Gender
All
Age
40 Years to 70 Years
Inclusion criteria
Inclusion criteria: 1. Aged 40~70 years old; 2. Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology or cytology are not suitable for surgery or local treatments (including ablation, interventional and radiotherapy), and have progressed or become intolerant after receiving standard treatments in the past Affected patients; 3. The previous PD-1 monoclonal antibody treatment was ineffective and the treatment was terminated for more than 28 days; 4. According to the RECIST1.1 standard, there is at least one target lesion that can be evaluated stably, which is defined as: the longest diameter of non-lymph node lesions >=10 mm, or the short diameter of lymph node lesions >=15 mm; the intrahepatic lesions require arterial phase enhanced imaging; 5. The tumor tissue sample was tested positive for GPC3 by immunohistochemistry (IHC); 6. According to the Barcelona Liver Cancer Grading Standard (BCLC), it is classified as Grade C or Grade B that is not suitable for local treatment/local treatment progress; 7. Estimated survival time> 12 weeks; 8. Child-Pugh score of liver cirrhosis A grade; 9. ECOG physical status score 0~1; 10. If the patient is HBsAg positive or HBcAb positive, HBV-DNA =2.5x10^9/L, PLT>=60x10^9/L, Hb>=9.0 g/dL, LY>=0.4x10^9/L; 13. Blood biochemistry: serum Alb >=30 g/L, serum lipase and amylase =40mL/min, ALT<=5 ULN, AST<=5 ULN, total bilirubin Element <=2.5 ULN, prothrombin time extension <=4 s; 14. Female subjects of childbearing age must undergo a serum pregnancy test within 14 days before the screening period and start of study medication, and the result is negative, and are willing to use reliable methods of contraception during the test period (within 12 months after cell infusion (M12)); For male subjects whose partners are women of childbearing age, they should have undergone sterilization or agreed to use reliable methods of contraception during the trial; 15. Able to understand and sign informed consent.
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria cannot be selected for this study: 1. Pregnant or lactating women; 2. HCV-RNA, HIV antibody or syphilis antibody test is positive; 3. Any uncontrollable active infection, including but not limited to active tuberculosis; 4. Received systemic steroids equivalent to >15 mg of prednisone within 2 weeks before apheresis, except for inhaled steroids; 5. Allergy to immunotherapy and related drugs, previous history of severe allergy, allergy to ß-lactam antibiotics; 6. Past or present hepatic encephalopathy; 7. There is currently clinically significant ascites, which is defined as: ascites with positive signs of ascites on physical examination or ascites that requires intervention (for example, paracentesis or drug therapy) to control (only those with ascites shown by imaging and without intervention are acceptable Included); 8. The results of imaging examination: The proportion of liver being replaced by tumor >=50%, or tumor thrombus in the main portal vein, or tumor thrombus invading the mesenteric vein/inferior vena cava; 9. Central nervous system metastasis and central nervous system diseases of clinical significance; 10. At present, there is a heart disease requiring treatment or a poorly controlled hypertension (systolic blood pressure>160mmHg or diastolic blood pressure>100mmHg) as judged by the researcher; 11. Patients with known active autoimmune diseases need to be treated with immunosuppressive agents including biological agents; 12. Patients who have a history of organ transplantation or are waiting for organ transplantation (including liver transplantation); 13. The treatment for the research disease has been carried out within 2 weeks before apheresis, including but not limited to: surgical treatment, interventional treatment, radiotherapy, chemotherapy and immunotherapy; 14. Received targeted GPC3 therapy, TCR-T therapy, CAR-T therapy within the past 1 month; 15. Have been receiving anti-PD-1/PD-L1 monoclonal antibody treatment within the past 28 days; 16. Suffered from other uncured malignant tumors in the past 5 years or at the same time, except for cervical cancer in situ and basal cell carcinoma of the skin; 17. Other serious diseases that may restrict subjects from participating in this trial (such as poorly controlled diabetes (after treatment with glycosylated hemoglobin HbA1c> 7%), severe cardiac insufficiency (left ventricular ejection fraction (LVEF) <45%) , Myocardial infarction or unstable arrhythmia or unstable angina pectoris, pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease, pulmonary function test FEV1 accounted for <60% of the expected value in the past 6 months, gastric ulcer, A history of gastrointestinal bleeding or a clear tendency to gastrointestinal bleeding); 18. The investigator assessed that the patient was unable or unwilling to comply with the requirements of the research protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| safety and tolerability; | — |
Countries
China
Contacts
Public ContactWeizhong Wu
Zhongshan Hospital, Fudan University
Outcome results
None listed