Safety and Efficacy Evaluation of IM83 CAR-T Cells for Patients With Advanced Liver Tumors

Inclusion Criteria:

• ≥ 18 years old, male or female.
• Patients with advanced hepatocellular carcinoma (HCC) diagnosed by histopathology orcytology, Barcelona stage B-C.
• Progression or intolerance after receiving standardized systematic treatment in thepast (at least first-line treatment fails, and PD-1 / PD-L1 drugs can be used).
• Patients in car-t combined treatment group need to have not received the combineddrugs before.
• At least one measurable target lesion according to RECIST1.1.
• Tumor cells expressed GPC3 antigen.
• Child Pugh score of liver function ≤ 7.
• ECOG 0-1.
• Estimated survival ≥ 12 weeks;
• Laboratory inspection shall at least meet the following specified indicators: ANC≥ 1.5 × 10 ^ 9 / L，platelet ≥ 75 × 10 ^ 9 / L ，Hemoglobin ≥ 90 g / L，Serum creatinine ≤ 1.5 ULN，serum bilirubin ≤ 3 ULN，INR≤ 2，AST and ALT)≤ 5.0 ULN，Creatinine clearance rate ≥ 60ml / min.
• The left ventricular ejection fraction was > 50%.

Exclusion Criteria:

• The researcher has determined that the subject has autoimmune diseases that are notsuitable to participate in this study, such as systemic lupus erythematosus,rheumatoid arthritis, ulcerative colitis.
• History of epilepsy or other central nervous system diseases that may affect the testin the judgment of the investigator.
• The washout period of chemotherapy, molecular targeted therapy, immunotherapy, hepaticartery chemoembolization, radiofrequency ablation, radiotherapy for non target lesionsor other anti-tumor drugs within 1 week before blood collection is less than 5 halflives.
• Systemic glucocorticoids (local use is allowed) or other immunosuppressants were usedwithin 3 days before apheresis.
• Other incurable malignant tumors in the past 5 years or at the same time, exceptcervical carcinoma in situ, skin basal cell carcinoma and breast ductal carcinoma insitu.
• The investigator assessed that the subject had poorly controlled pleural effusion,ascites or pericardial effusion.
• Hypertension with poor drug control (systolic blood pressure > 160mmhg and / ordiastolic blood pressure > 90mmHg) or cardiovascular and cerebrovascular diseases withclinical significance (such as active) within 6 months before signing the informedconsent, such as cerebrovascular accident, myocardial infarction, unstable anginapectoris, or severe arrhythmia, which cannot be controlled by drugs or has potentialimpact on the study treatment.
• Combined with other serious organic diseases or mental diseases.
• Subjects with HBsAg or HBcAbpositive and peripheral blood HBV DNA titers of >2000IU/ml (HBsAg positive but HBV DNA titer <2000 IU/ml of peripheral blood and eligiblefor antiviral treatment according to chronic hepatitis B prevention guideline 2019Edition). HCV antibody positive and HCV RNA in peripheral blood > 500 IU / ml.Syphilis antibody positive.
• Male subjects who are pregnant or breastfeeding during the screening period, or whoplan pregnancy during treatment or within 1 year after the end of treatment, or whosepartner plans pregnancy within 1 year after the end of treatment.
• There were active or uncontrollable infections requiring systemic treatment within 1week before cell apheresis.
• Other researchers believe that it is not suitable for inclusion.