Inclusion Criteria:
1. For unresectable or metastatic or postoperative recurrence, histologically confirmed advanced ICC, provide enough tissue samples for PD-L1, CTLA-4 immunohistochemistry, and exome sequencing
2. The standard systemic treatment of advanced ICC (gemcitabine or platinum or fluorouracil) failed due to disease progression or toxicity
3. There are measurable lesions defined by RECIST standard v1.1
4. For patients with a history of liver chemoembolization, radiofrequency ablation/intervention, or radiotherapy, there must be measurable lesions outside the chemoembolization or radiotherapy area or measurable progression lesions at the chemoembolization or radiotherapy site
5. ECOG physical strength status ≤ 1
6. Life expectancy\> 3 months
7. Adequate renal function: creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60mL/min/1.73 m2
8. Sufficient liver function: bilirubin ≤ 1.5 × ULN and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × ULN
9. Sufficient bone marrow reserve: absolute value of neutrophils (ANC)\> 1500/mcl, platelets (Plts)\> 75,000/mcl, hemoglobin (Hgb) ≥ 9.0g/dl
10. Prothrombin time/activated partial thromboplastin time (PT/PTT) \<1.5 × ULN
11. Age ≥18 years old
12. HBV infected persons must meet the following criteria to be eligible to participate in the study:
Chronic hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen \[HBsAg\] positive and/or detectable HBV DNA) subjects must have HBV viral load below 2000 IU/ml before the first dose of the study intervention. Active HBV-treated subjects with a viral load of less than 2000 IU/ml should receive antiviral therapy throughout the study intervention period and check the HBV viral load every 6 weeks. Subjects whose HBV infection is clinically cured (defined as HBsAg negative and anti-HBc positive) and whose HBV viral load cannot be detected during screening should be checked for HBV viral load every 6 weeks. If the viral load exceeds 2000 IU/ml, HBV treatment should be carried out. Antiviral treatment after completing the research intervention should follow local guidelines.
13. The toxicity of the previous treatment has been restored to ≤1 grade (if there is surgery, the wound has completely healed)
14. Female subjects of childbearing age must undergo a pregnancy test within 2 weeks before starting the study medication, and the result is negative, and are willing to use a medically approved high-efficiency contraceptive method during the study period and within 24 weeks after the last study drug administration (Such as intrauterine device, contraceptive pills or condoms); for male subjects whose partners are females of childbearing age, they should agree to use effective methods of contraception during the study period and within 24 weeks after the last study administration
15. Subjects voluntarily joined the study, signed an informed consent form, had good compliance, and cooperated with follow-up.
Exclusion Criteria:
1. Past treatment with CTLA-4 mAb
2. Hilar cholangiocarcinoma or extrahepatic cholangiocarcinoma or periampullary carcinoma or gallbladder cancer
3. Major surgery or radiotherapy within 4 weeks before enrollment
4. Active, known, or suspected autoimmune diseases
5. Congestive heart failure or symptomatic coronary artery disease within 3 months before enrollment
6. Cerebrovascular accident occurred in the past 6 months
7. Clinically significant bleeding, bleeding event, or thromboembolic disease occurred within 6 months
8. History of bowel perforation
9. A history of (non-infectious) pneumonia requiring steroid treatment or current pneumonia
10. Known history of human immunodeficiency virus (HIV) infection
11. History of severely impaired lung function or interstitial lung disease
12. Diagnosed concurrent malignant tumors in the past 5 years (except for fully treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder and cervical carcinoma in situ \[CIS\]) or any currently active malignant tumors
13. HCV RNA positive test indicates the active period
14. Patients who have previously received allogeneic bone marrow transplantation or solid organ transplantation
15. Uncontrollable or symptomatic hypercalcemia
16. Known uncontrollable or symptomatic active central nervous system (CNS) metastasis
17. Symptomatic advanced patients who are at risk of life-threatening complications in the short term (including patients with uncontrollable large amounts of exudate \[thoracic cavity, pericardium, abdominal cavity\])
18. Known allergies to study drugs or excipients or known severe allergic reactions to any monoclonal antibody
19. Severe infections during screening, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc.
20. Have received any other experimental drug treatment or participated in another interventional clinical study within 4 weeks before signing the ICF
21. Live attenuated vaccine within 4 weeks before enrollment or planned during the study period and 60 days after the end of study drug treatment
22. Known mental illness, alcohol abuse, inability to quit smoking, drug or drug abuse, etc.
23. Past or current evidence indicates that any conditions, treatments, or laboratory abnormalities that may confuse the research results, interfere with the subject's participation in the entire research process, or the researcher believes that participating in this research is not in the subjects' best interests.
