A Trial of Cadonilimab Plus Regorafenib in Patients With Hepatocellular Carcinoma Who Failed Camrelizumab Combined With Apatinib

Inclusion Criteria:

1. Sign a written informed consent form before enrollment;
2. Age \>18 years old, both sex;
3. Histological or pathological confirmed intermediate or advanced hepatocellular carcinoma, or patients with cirrhosis who meet the clinical diagnostic criteria for hepatocellular carcinoma of the American Association for the Study of Liver Diseases (AASLD);
4. Have progressed on the combination treatment of camrelizumab and apatinib for HCC
5. Child-Pugh Class A;
6. ECOG PS score: 0\~1;
7. At least 1 measurable lesion (RECIST1.1)
8. Expected survival period≥12 weeks
9. The function of vital 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 ≥75×109/L Hemoglobin ≥ 90g/L; 2. Liver and kidney function: Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 10 times the upper limit of normal (ULN); urine protein \< 2+; if urine protein ≥ 2+, 24-hour urine protein quantification shows that the protein must be ≤ 1g; 10. Normal coagulation function, no active bleeding or thrombosis disease

1. International normalized ratio INR≤1.5×ULN;
2. Partial thromboplastin time APTT≤1.5×ULN;
3. Prothrombin time PT≤1.5×ULN; 11. Non-surgical sterilization or female patients of childbearing age 12. Subjects voluntarily join this study, have good compliance, and cooperate with safety and survival follow-up

Main Exclusion Criteria:

1. Containing components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma that have been previously confirmed by histology/cytology;
2. Have a history of hepatic encephalopathy;
3. Have a history of liver transplantation;
4. There is clinically significant pericardial effusion, and there are clinical symptoms of pleural effusion that require drainage;
5. Clinically apparent ascites is defined as meeting the following criteria: ascites can be detected by physical examination during screening or ascites needs to be drained during screening;
6. Simultaneous infection with HBV and HCV (having a history of HCV infection but negative HCV RNA can be considered as not being infected with HCV);
7. Presence of central nervous system metastasis or meningeal metastasis
8. Bleeding from esophageal or gastric varices caused by portal hypertension has occurred within 6 months before the first dose
9. Patients with any bleeding or bleeding event ≥CTCAE grade 3 within 4 weeks before the first dose
10. Arterial and venous thromboembolic events occurred within 6 months before the first dose
11. Uncontrolled high blood pressure
12. Symptomatic congestive heart failure
13. Severe bleeding tendency or coagulation disorder
14. Have a history of gastrointestinal perforation and/or fistula, intestinal obstruction within 6 months before the first dose
15. Active autoimmune disease or a history of autoimmune disease
16. Patients with HIV
17. According to the investigator's judgment, patients with other serious concomitant diseases that endanger the patient's safety or affect the patient's completion of the study.