HAIC Combined With Second-line "Target Immunity" for HCC With TACE Standard Treatment Low Response or Failure

Inclusion Criteria:

* Voluntarily participate in this study and sign the informed consent;
* Age ≥18 years old to 70 years old;
* Patients diagnosed with primary liver cancer by histopathology, cytology or imaging;
* The China liver cancer staging is IIb-IIIa;
* Patients with intermediate and advanced liver cancer who must receive at least one cycle of TACE combined with first-line "target immune" therapy and are assessed as partial remission (PR), stable disease (SD）(low response), and progressive disease (PD) (failure) according to mRECIST criteria;
* At least one measurable (based on RECIST 1.1 criteria and mRECIST criteria) lesions, tumor lesions located at the local treatment site, if progressed, considered measurable;
* Local treatment (surgery, radiotherapy, radiofrequency/microwave ablation, cryoablation, percutaneous ethanol injection) can be used in the past, but it must be completed before 3 months;
* ECOG PS score ≤ 2;
* Child-Pugh liver function classification: grade A/B (≤9 points);
* Expected survival \> 3 months;
* Patients with active hepatitis B virus (HBV) infection: HBV DNA ≤2000 IU/mL (104 cps/ml) obtained within 28 days prior to initiation of study treatment, and receiving anti-HBV treatment for at least 14 days prior to study entry (based on local standard treatment) and willing to continue to receive treatment during the study;

Exclusion Criteria:

* Have received HAIC treatment in the past;
* Known allergy to possible therapeutic drugs;
* Previously received regorafenib treatment;
* According to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), the toxicity grade caused by TACE combined with first-line "target immunity" treatment is \> grade 3;
* Patients with liver decompensation, including esophageal or gastric variceal bleeding or hepatic encephalopathy, pregnancy or breastfeeding and other aggressive malignant diseases;
* Use immunosuppressive drugs and high-dose hormone therapy within 2 weeks before randomization to achieve the purpose of immunosuppression (dose\>10mg/day prednisone or other hormones with equivalent efficacy);
* CART treatment within 3 months before randomization;
* Laboratory test values 1 week before randomization: blood routine: ① leukocyte \<3.0×109/L; ② absolute neutrophil count \<1.5×109/L; ③ platelets \<75×109/L; ④ hemoglobin \< 90g/L; liver function: ①serum albumin\<30g/L; ②ALT and AST\>5×ULN; renal function: ①serum creatinine\>1.5×ULN; ②Cr clearance rate\<50ml/min; ③estimated renal small Globular filtration rate (eGFR) \<30 mL/min/1.73 m2; coagulation function: ① international normalized ratio (INR)\> 2; ② prothrombin time (PT) exceeding the range of normal control\> 6 seconds;
* Uncontrolled hypertension (systolic blood pressure \> 180 mmHg, diastolic blood pressure \> 110 mmHg);
* Uncontrollable diabetes;
* Active heart disease, including myocardial infarction, unstable angina pectoris, NYHA class II and above heart failure, and poorly controlled arrhythmias (including QTcF interval \>450 ms in men and \>470 ms in women);
* Women are pregnant or breastfeeding;
* History of any active autoimmune disease or autoimmune disease, including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, vasculitis, glomerulonephritis, hyperthyroidism, or hypothyroidism, asthma requiring bronchodilator treatment, etc;
* Uncontrolled clinically significant ascites (uncontrolled with diuretics or paracentesis);
* Combined with active infection, except HBV and HCV;
* Arterial or venous thrombosis or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep venous thrombosis or pulmonary embolism, occurred 6 months before starting drug treatment;
* Known central nervous system (CNS) metastasis or meningeal metastasis;
* The patient cannot receive follow-up or is participating in other clinical trials;
* The investigator believes that the patient has other conditions that make it inappropriate to participate in this study.