Phase I Clinical Trial of CT0180 Cells in the Treatment of Hepatocellular Carcinoma

Primary objectives:

Evaluate the safety and tolerance of CT0180 cells in patients with advanced hepatocellular carcinoma within 28 days after the first infusion

Secondary objectives:

• Evaluate the metabolic kinetics of CT0180 cells ; · Evaluate overall safety and tolerability ; · Evaluate the initial efficacy of CT0180 cell infusion in the treatment of advanced hepatocellular carcinoma with positive Glypican-3（GPC3 ）expression.

Inclusion criteria

• Aged 18 to 75 years, either sex；
• Patients with clinically or pathologically confirmed hepatocellular carcinoma were treated with surgery or local treatment It is not suitable for surgery or local radical treatment;
• Progression or intolerance after at least one previous systemic treatment, or due to specific reasons unable to receive systemic treatment. Systemic therapy can include: Programmed Death 1（PD-1） / programmed cell death-Ligand 1（PD-L1） monoclonal antibody Antibodies, molecular targeted drugs (e.g. sorafenib, regofinib, renvastinib)and conventional chemotherapy, etc;
• According to Barcelona Clinic Liver Cancer（BCLC）, the patients are classified into Grade C or Grade B unsuitable for local treatment/progressive disease after local treatment;
• In tumor tissue samples GPC3 is detected positive by immunohistochemistry (IHC);
• According to Response Evaluation Criteria in SolidTumors（RECIST1.1）,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;
• Expected survival is > 12 weeks;
• Cirrhosis status Child-Pugh score: Grade A;
• Eastern Cooperative Oncology Group（ ECOG） Performance Status score: 0 to 1 point;
• If the patient is HBsAg positive or HBcAb positive, HBV-DNA should be <2000 IU/ml. HBsAg positive patients must receive antiviral treatment ;
• Acceptable routine blood test showing no contraindication to the lymphodepletion pretreatment and adequate liver, renal, cardiovascular, respiratory function;
• Have venous accesses for apheresis;
• 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 52 weeks 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;
• Understand and sign informed consent.

Exclusion criteria

• Pregnant or breast-feeding women;
• Hepatitis virus C antibodies ,human immunodeficiency virus（HIV） antibodies or Syphilis Serological tests are positive;
• Any uncontrol active infection, including but not limited to active tuberculosis;
• Have clinically significant thyroid dysfunction except the stable control after treatment;
• Previous or present hepatic encephalopathy;
• Current clinically significant ascites;
• Imaging results:≥50% of the liver is replaced by tumor or portal vein main tumor thrombus, or metastases to the central nervous system, or tumor thrombus invasion of mesenteric vein / inferior vena cava;
• Patients with a history of organ transplantation or waiting for organ transplantation (including liver transplantation);
• The side effects caused by the previous treatment of the subjects did not return to Common Terminology Criteria for Adverse Events（CTCAE） ≤1; except hair loss and other tolerable events determined by investigator;
• Patients who had received systemic steroids or other immunosuppressive agents within 7 days before apheresis, except inhaled steroids;
• History of severe allergy ,allergic to CT0180 cell fluid adjuvant such as Dimethyl sulfoxide（DMSO）;
• Has signs of central nervous system disease or an abnormal neurological examination with clinical significance;
• Subjects with unstable or active ulcers, gastrointestinal bleeding, or pump inhibitor intolerance;
• Patients with a history of organ transplantation or waiting for organ transplantation;
• Previously received anti-PD-1/ PD-L1 monoclonal antibody therapy within 4 weeks or local treatment and systemic chemotheray within 2 weeks or immunotheray and molecular targeted drugs within 1 week before apheresis;
• Previously received GPC3 targeted therapy;
• Major surgery or significant trauma occurred within 4 weeks before apheresis, or it is expected that major surgery needs to be performed during the trial;
• Patients who had incurable malignant tumors in the past 5 years or at the same time, except cervical cancer in situ and basal cell carcinoma of skin;
• Other serious diseases that may restrict the subjects from participating in the trial ；
• The researcher assessed that the subjects were unable or unwilling to comply with the requirements of the trial protocol.