Cadonilimab in Combination With Ramucirumab for the Treatment of Advanced Hepatocellular Carcinoma That Has Failed at Systemic Therapy

Inclusion Criteria:

1. written informed consent signed prior to enrolment.
2. age > 18 years, both sexes
3. patients with histologically or pathologically confirmed intermediate to advancedhepatocellular carcinoma.
4. Previously received systemic drug treatment for HCC, with disease progression orintolerable toxicity
5. Child-Pugh A or B7
6. with measurable lesions (≥10 mm long diameter on CT scan for non-lymph node lesionsand ≥15 mm short diameter on CT scan for lymph node lesions according to RECIST 1.1criteria).
7. ECOG PS score: 0 to 1.
8. expected survival of >12 weeks.
9. function of vital organs in accordance with the following requirements (excluding theuse of any blood components and cell growth factors within 14 days).

1. Blood count. Neutrophils ≥ 1.5 x 109/L Platelet count ≥ 60×109/L haemoglobin ≥ 90 g/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) Glutamic aminotransferase (AST) or glutamic aminotransferase (ALT) levels ≤ 10 times the upper limit of normal (ULN);urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantification must show ≤ 1 g of protein.

10. normal coagulation function, no active bleeding or thrombotic disease
11. International normalised ratio INR ≤ 1.5 x ULN.
12. partial thromboplastin time APTT ≤ 1.5 x ULN.
13. prothrombin time PT ≤ 1.5 x ULN. 11. Female patients who are non-surgically sterilisedor of childbearing age are required to use a medically approved contraceptive (e.g.IUD, pill or condom) during and for 3 months after the end of the study treatmentperiod; female patients of childbearing age who are non-surgically sterilised musthave a negative serum or urine HCG test within 7 days prior to study entry; and mustbe non-lactating; male patients who are non-surgically sterilised or of childbearingage Patients, need to agree to use a medically approved form of contraception withtheir spouse during and for 3 months after the end of the study treatment period.
14. The subject is voluntarily enrolled in the study, is compliant and cooperates withsafety and survival follow-up

Exclusion Criteria: Patients with any of the following are not eligible for enrollment in this study.

1. Subjects with previous or concurrent other malignancies (except cured basal cellcarcinoma of the skin and carcinoma in situ of the cervix).
2. the subject has received previous immunotherapy other than anti-PD-1/PD-L1 monoclonalantibody; the subject is known to have a previous allergy to macromolecular proteinagents, or is known to be allergic to the components of the drug applied.
3. The subject has any active autoimmune disease or history of autoimmune disease (e.g.the following, but not limited to: autoimmune hepatitis, interstitial pneumonia,uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis,hyperthyroidism, hypothyroidism, previous thyroid surgery cannot be included; thesubject has vitiligo or has complete remission of asthma in childhood and in adulthood (subjects who do not require any intervention can be included; subjects with asthmarequiring medical intervention with bronchodilators cannot be included).
4. subjects who are on immunosuppressive, or systemic, or absorbable topical hormonetherapy for immunosuppressive purposes (doses >10 mg/day of prednisone or otherisotonic hormones) and who continue to use them within 2 weeks prior to enrolment
5. have clinically symptomatic ascites or pleural effusion requiring therapeutic punctureor requiring frequent drainage of ascites (≥1 time/month)
6. subjects with clinically symptomatic cardiac conditions or diseases that are not wellcontrolled, such as (1) NYHA class 2 or higher heart failure (2) unstable anginapectoris (3) previous myocardial infarction within 1 year (4) patients with clinicallysignificant supraventricular or ventricular arrhythmias requiring treatment orintervention
7. subjects with active infection or unexplained fever >38.5 degrees during screening andprior to the first dose (subjects with fever arising from a tumour may be enrolled, asjudged by the investigator)
8. patients with previous and current objective evidence of a history of pulmonaryfibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-relatedpneumonia, or severely impaired lung function
9. subjects with congenital or acquired immune deficiency, e.g. HIV infection
10. subjects who have received a live vaccine less than 4 weeks prior to study drugadministration or possibly during the study period
11. subjects with a known history of psychotropic substance abuse, alcoholism or drug use
12. patients who are unable to administer the drug orally
13. have received herbal or proprietary Chinese medicine with an anti-tumour indicationwithin 2 weeks prior to the first dose .

14 Patients who, in the opinion of the investigator, should be excluded from the study, forexample, subjects who, in the judgment of the investigator, have other factors that mayforce the study to be terminated, e.g., other serious illnesses (including psychiatricillnesses) requiring comorbid treatment, severe fundic esophageal varices, seriouslaboratory test abnormalities, accompanying family or social factors that would compromisethe safety of the subject, or the collection of data and samples.