Overview

To evaluate the efficacy and safety of Cadonilimab Injection in combination with Regorafenib in the treatment of intermediate to advanced hepatocellular carcinoma that has failed at least one prior systemic therapy .

Eligibility

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 advanced hepatocellular carcinoma.
4. intermediate to advanced HCC previously treated with anti-PD-1/PD-L1 combined with anti-vascular targeting agents for HCC, with disease progression.
5. Child-Pugh A or B.
6. with measurable lesions (≥10 mm long diameter on CT scan for non-lymph node lesions and ≥15 mm short diameter on CT scan for lymph node lesions according to RECIST 1.1 criteria).
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 the use 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
          1. International normalised ratio INR ≤ 1.5 x ULN.
          2. partial thromboplastin time APTT ≤ 1.5 x ULN.
          3. prothrombin time PT ≤ 1.5 x ULN. 11. Female patients who are non-surgically sterilised
             or 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 treatment
             period; female patients of childbearing age who are non-surgically sterilised must
             have a negative serum or urine HCG test within 7 days prior to study entry; and must
             be non-lactating; male patients who are non-surgically sterilised or of childbearing
             age Patients, need to agree to use a medically approved form of contraception with
             their spouse during and for 3 months after the end of the study treatment period.
        12. The subject is voluntarily enrolled in the study, is compliant and cooperates with
        safety and survival follow-up Exclusion criteria： 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 cell
             carcinoma of the skin and carcinoma in situ of the cervix).
          2. the subject has received previous immunotherapy other than anti-PD-1/PD-L1 monoclonal
             antibody; the subject is known to have a previous allergy to macromolecular protein
             agents, 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; the
             subject 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 asthma
             requiring medical intervention with bronchodilators cannot be included).
          4. subjects who are on immunosuppressive, or systemic, or absorbable topical hormone
             therapy for immunosuppressive purposes (doses >10 mg/day of prednisone or other
             isotonic hormones) and who continue to use them within 2 weeks prior to enrolment
          5. have clinically symptomatic ascites or pleural effusion requiring therapeutic puncture
             or requiring frequent drainage of ascites (≥1 time/month)
          6. subjects with clinically symptomatic cardiac conditions or diseases that are not well
             controlled, such as (1) NYHA class 2 or higher heart failure (2) unstable angina
             pectoris (3) previous myocardial infarction within 1 year (4) patients with clinically
             significant supraventricular or ventricular arrhythmias requiring treatment or
             intervention
          7. subjects with active infection or unexplained fever >38.5 degrees during screening and
             prior to the first dose (subjects with fever arising from a tumour may be enrolled, as
             judged by the investigator)
          8. patients with previous and current objective evidence of a history of pulmonary
             fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related
             pneumonia, 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 drug
             administration 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 indication
             within 2 weeks prior to the first dose .
        14 Patients who, in the opinion of the investigator, should be excluded from the study, for
        example, subjects who, in the judgment of the investigator, have other factors that may
        force the study to be terminated, e.g., other serious illnesses (including psychiatric
        illnesses) requiring comorbid treatment, severe fundic esophageal varices, serious
        laboratory test abnormalities, accompanying family or social factors that would compromise
        the safety of the subject, or the collection of data and samples.