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 hepatocellularcarcinoma, or patients with cirrhosis who meet the clinical diagnostic criteria forhepatocellular 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 ofany blood components and cell growth factors within 14 days):

10. 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 ofnormal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); Totalbilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN); Aspartateaminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 10 times the upperlimit of normal (ULN); urine protein < 2+; if urine protein ≥ 2+, 24-hour urineprotein quantification shows that the protein must be ≤ 1g; 10. Normal coagulationfunction, no active bleeding or thrombosis disease

11. International normalized ratio INR≤1.5×ULN;

12. Partial thromboplastin time APTT≤1.5×ULN;

13. Prothrombin time PT≤1.5×ULN; 11. Non-surgical sterilization or female patients ofchildbearing age 12. Subjects voluntarily join this study, have good compliance, andcooperate with safety and survival follow-up

Main Exclusion Criteria:

1. Containing components such as fibrolamellar hepatocellular carcinoma, sarcomatoidhepatocellular carcinoma, and cholangiocarcinoma that have been previously confirmedby 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 clinicalsymptoms of pleural effusion that require drainage;

5. Clinically apparent ascites is defined as meeting the following criteria: ascitescan be detected by physical examination during screening or ascites needs to bedrained during screening;

6. Simultaneous infection with HBV and HCV (having a history of HCV infection butnegative 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 hasoccurred within 6 months before the first dose

9. Patients with any bleeding or bleeding event ≥CTCAE grade 3 within 4 weeks beforethe first dose

10. Arterial and venous thromboembolic events occurred within 6 months before the firstdose

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, intestinalobstruction 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 concomitantdiseases that endanger the patient's safety or affect the patient's completion ofthe study.