Overview

To evaluate the efficacy and safety of Cadonilimab Injection in combination with Regorafenib in the treatment of intermediate to advanced biliary systemic tumours 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 Biliary Systemic Tumours
4. Failed at least one prior systemic therapy
5. 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).
6. ECOG PS score: 0 to 1.
7. expected survival of >12 weeks.
8. 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.
        9. 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. 10. 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.
        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.
        11.Clinical diagnosis of Alzheimer's Disease 12. Must be able to swallow tablets 13. The
        subject is voluntarily enrolled in the study, is compliant and cooperates with safety 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 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 with Insulin dependent diabetes
              15. Patients with hyroid disease
              16. 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.