Comparing the Combination of Trastuzumab and Regorafenib With Regorafenib Monotherapy for Advanced Hepatocellular Carcinoma After First-line Treatment

Inclusion Criteria:

* Sign a written informed consent form;
* Age ≥ 18 years old, both male and female are eligible;
* Hepatocellular carcinoma (HCC) diagnosed by organization/pathology or imaging that meets the AASLD diagnostic criteria;
* HCC that has received targeted immunotherapy in the past (regardless of whether local treatment is received or not, excluding neoadjuvant therapy), including atezolizumab+bevacizumab, sintilizumab+bevacizumab analogs, carizolizumab+apatinib, and other PD-1/L1 drugs+TKI, and whose disease progression has been confirmed by imaging;
* Child Pugh score ≤ 7;
* According to RECIST 1.1 criteria, there must be at least one measurable lesion;
* ECOG PS score 0-1;
* Expected survival period greater than 12 weeks;
* The function of important organs meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days):

  1. Blood routine:

     Neutrophils ≥ 1.5 × 109/L Platelet count ≥ 80 × 109/L Hemoglobin ≥ 90g/L;
  2. Liver and kidney function:

Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance rate ≥ 50 ml/min (Cockcroft Gault formula); Total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN); AST or ALT levels ≤ 5 times the upper limit of normal (ULN); Urinary protein\<2+; If urine protein is ≥ 2+, the 24-hour urine protein quantification must show protein ≤ 1g;

* Normal coagulation function, no active bleeding or thrombotic diseases

  1. International Standardization Ratio INR ≤ 1.5 × ULN;
  2. Partial thromboplastin time APTT ≤ 1.5 × ULN;
  3. Prothrombin time PT ≤ 1.5 × ULN;
* Non surgical sterilization or female patients of childbearing age are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 3 months after the end of the study treatment period; Female patients of childbearing age who undergo non-surgical sterilization must have a negative serum or urine HCG test within 7 days prior to enrollment in the study; And it must be during non lactation period; Non surgical sterilization or male patients of childbearing age need to agree to use a medically approved contraceptive measure with their spouse during the study treatment period and within 3 months after the end of the study treatment period.

Exclusion Criteria:

* The subject has previous or concurrent malignant tumors (excluding cured skin basal cell carcinoma and cervical carcinoma in situ);
* It is known that the subject has a history of allergies to large molecule protein preparations, or is known to be allergic to the investigational drug or drug components;
* Within the past 6 months, there have been incidents of esophageal or gastric variceal bleeding caused by portal hypertension; Within 3 months prior to the first administration, severe (G3) varicose veins were identified through endoscopic examination; Evidence of portal hypertension (including imaging findings of splenomegaly), assessed by researchers as high-risk for bleeding
* Any life-threatening bleeding events that have occurred within the past 3 months, including the need for blood transfusion therapy, surgery or local treatment, and continuous medication therapy
* Subjects with any active autoimmune disease or history of autoimmune disease (such as but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, those who have undergone thyroid surgery in the past cannot be included; subjects with vitiligo or complete remission of childhood asthma without any intervention in adulthood can be included; subjects with asthma requiring bronchodilators for medical intervention cannot be included);
* The subject is currently using immunosuppressants, systemic, or absorbable local hormone therapy to achieve immunosuppression (dose\>10mg/day prednisone or other therapeutic hormones), and has continued to use it within 2 weeks before enrollment;
* Ascites or pleural effusion with clinical symptoms that require therapeutic puncture or regular drainage (≥ 1 time/month);
* Patients with uncontrolled clinical symptoms or diseases of the heart, such as: (1) NYHA grade 2 or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, and (4) clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
* The subject has an active infection or an unexplained fever greater than 38.5 degrees Celsius during the screening period or before the first administration (according to the researcher's judgment, the subject can be included if the fever is caused by the tumor);
* Patients with objective evidence of past and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc;
* Subjects with congenital or acquired immune dysfunction, such as HIV infected individuals;
* Within less than 4 weeks before the study medication, or possibly during the study period, receiving a live vaccine;
* The subject is known to have a history of substance abuse, alcoholism, or drug use;
* Have received Chinese herbal medicine or traditional Chinese patent medicines and simple preparations with anti-tumor indications within 2 weeks before the first administration.