A Study of the Application of HAIC in Advanced HCC Previously Treated With ICIs and Antiangiogenic Agents

Inclusion Criteria: Cytohistological confirmation is required for diagnosis of HCC. Patients with advanced (unresectable and/or metastatic, stage C based on Barcelona-Clinic Liver Cancer [BCLC]staging classification) hepatocellular carcinoma. At least one tumor lesion meeting measurable disease criteria as determined by RECIST v1.1. Current cirrhotic status of Child-Pugh class A-B, with no encephalopathy. Ascitescontrolled by diuretics is permitted in this study. Availability of a representative tumor tissue specimen (archival tumor tissue is allowed)at pre-screening. Eastern Cooperative Oncology Group Scale for Assessment of Patient Performance Status ≤ 2. Both men and women enrolled in this trial must use adequate barrier birth control measuresduring the course of the trial and 4 weeks after the completion of trial. Adequate bone marrow, liver and renal function as assessed by central lab by means of thefollowing laboratory requirements from samples within 7 days prior to procedure: Hemoglobin > 100g/L Absolute neutrophil count >3.0 ×109/L Neutrophil count > 1.5 ×109/LPlatelet count ≥ 50.0 ×109/L Total bilirubin < 51 μmol/L Alanine transaminase (ALT) andaminotransferase (AST) < 5 x upper limit of normal Albumin > 28 g/L Prothrombin time (PT)-international normalized ratio (INR) < 2.3, or PT < 6 seconds above control Serumcreatinine < 110 μmol/L Willing and able to comply with scheduled visits, treatment planand laboratory tests.

Exclusion Criteria: Local treatments for HCC have been performed within 4 weeks, including surgical resection (including liver transplantation), local ablation, transcatheter arterial chemoembolization (TACE or TAE), radiotherapy (including brachytherapy). A history of liver decompensation, such as refractory ascites, gastrointestinal bleeding,or hepatic encephalopathy; Uncontrolled complications, including but not limited to:Persistent or activity (except the HBV and HCV) infection, symptoms of congestive heartfailure and uncontrolled diabetes, uncontrolled hypertension, unstable angina, uncontrolledarrhythmias, active ILD, severe chronic GI disease accompanied by diarrhea, or compliancewith requirements may limit the research, resulted in significant increase risk of AE orinfluence Subjects provided psychiatric/social problem status on their ability to providewritten informed consent. A history of active primary immunodeficiency or humanimmunodeficiency virus; Active or previous records of autoimmune disease or inflammatorydiseases, including inflammatory bowel disease (e.g., colitis or Crohn's disease],diverticulitis, except [diverticulosis], systemic lupus erythematosus (SLE), sarcoidosissyndrome or Wegener syndrome (e.g., granulomatous vasculitis, gray's disease, rheumatoidarthritis, the pituitary gland inflammation and uveitis]). Known to produce allergic or hypersensitive reactions to any study drug or any excipientthereof. Significant clinical gastrointestinal bleeding or a potential risk of bleeding wasidentified by the investigator during the 30 days prior to study entry. Tumors of the central nervous system, including metastatic brain tumors. Pregnant women orbreast-feeding patients. Complicated with other malignant tumors: Malignant tumors that have been treated for therapeutic purposes, have no known activedisease for 5 years prior to the first administration of the study drug, and have a lowpotential risk of recurrence. Fully treated non-melanoma skin cancer or malignant freckle moles with no evidence ofdisease. Fully treated carcinoma in situ without evidence of disease. Is currently using, or has used an immunosuppressive drug within 14 days prior to the firstdose of the investigational drug. This standard has the following exceptions: intranasal, inhaled, topical or topical steroids. (e.g., intraarticular) Systemiccorticosteroid therapy not exceeding 10 mg/ day of prednisone or its physiologicalequivalent as a prophylactic use of steroids for hypersensitivity. (e.g., CT scanpretherapy medication) Steroids as a prophylactic for allergic reactions. A live attenuatedvaccine was administered within 30 days prior to the first administration of the studydrug. Note: If enrolled, patients shall not receive live attenuated vaccine within 30 daysof receiving study drug therapy and after the last administration of study drug. Uncontrolled hypertension: systolic pressure ≥ 160 mmHg or diastolic pressure ≥ 100 mmHgdespite anti-hypertension medications ≤ 28 days before randomization or first dose of drug. Pregnant or lactating women, or fertile men or women who do not want to use high-efficiencycontraceptives, 6 months after the last dosing of study treatment, from screening to studytreatment. Based on the patient's preferred and customary lifestyle, abstinence duringtreatment and washout is an acceptable contraceptive method.