Cadonilimab With Chemotherapy in Treating Advanced Biliary Cancer

Exclusion Criteria

• •1. Diagnosis of malignant diseases other than extrahepatic bile duct cancer, excluding completely resected basal cell carcinoma, squamous cell carcinoma of the skin, and/or in situ carcinoma within the past 5 years.
• •2. Tumors located in the ampulla of Vater.
• •3. Currently participating in an interventional clinical study or received other investigational drugs or investigational device treatment within 4 weeks prior to the first dose of study drug.
• •4. Previously received therapy with anti-PD-1, anti-PD-L1, or anti-PD-L2 agents, or drugs targeting another T-cell receptor with inhibitory or co-stimulatory function (e.g., CTLA-4, OX-40, CD137).
• •5. Previously received palliative radiotherapy for biliary tumors, excluding postoperative adjuvant radiotherapy.
• •6. Received traditional Chinese medicine or immune modulatory drugs with anti-tumor indications within 2 weeks prior to the first dose of study drug (including thymosin, interferon, interleukins), except for local use to control pleural effusion.
• •7. Active autoimmune diseases requiring systemic treatment within 2 years prior to the first dose of study drug, or known history of primary immunodeficiency diseases. Patients with positive autoimmune antibodies alone will be evaluated by the investigator to determine if they have autoimmune diseases.
• •8. Currently receiving systemic corticosteroid therapy (excluding intranasal, inhaled, or topical corticosteroids) or any other form of immunosuppressive therapy within 4 weeks prior to the first dose of study drug. Physiological doses of corticosteroids (≤10 mg/day prednisone or equivalent) are permitted.
• •9. Uncontrolled pleural effusion or ascites that requires drainage or has not shown a significant increase in the past 3 days in patients who do not require drainage or whose drainage has been stopped.
• •10. Prior solid organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
• •11. Known hypersensitivity to the study drug, Candonilimab active substance, or excipients.
• •12. Insufficient recovery from any toxicities and/or complications related to previous interventions before starting treatment (i.e., ≤ Grade 1 or returning to baseline, excluding fatigue or alopecia).
• •13. Known history of human immunodeficiency virus (HIV) infection (i.e., positive for HIV 1/2 antibodies).
• •14. Untreated active hepatitis B defined as positive HBsAg and detectable HBV-DNA levels above the upper limit of normal at the study center. Note: The following HBV-infected patients may be included:
• •HBV viral load \<2.5 × 10\^3 copies/mL (500 IU/mL) prior to the first dose of study drug, and patients should receive anti-HBV therapy throughout the study treatment.
• •For patients who are anti-HBc positive, HBsAg negative, anti-HBs negative, and HBV DNA negative, no prophylactic anti-HBV therapy is required, but viral reactivation needs to be closely monitored.
• •15. Active hepatitis C infection (positive for hepatitis C virus (HCV) antibodies and HCV-RNA levels above the lower limit of detection).
• •16. Vaccination with live attenuated vaccines within 4 weeks prior to the first dose of study drug.
• •17. Pregnant or lactating women.
• •18. Presence of any severe or uncontrolled systemic diseases, including:
• •Resting electrocardiogram with significant and symptomatic abnormalities in rhythm, conduction, or morphology, such as complete left bundle branch block, grade II or higher cardiac conduction block, ventricular arrhythmia, or atrial fibrillation.
• •Unstable angina, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) classification ≥ Grade 2.
• •Any arterial thrombosis, embolism, or ischemia event within the past 6 months prior to enrollment, such as myocardial infarction, unstable angina, cerebrovascular accident, or transient ischemic attack.
• •Major surgery (e.g., craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study drug or unhealed wounds, ulcers, or fractures. Minor surgical procedures, including venous puncture for intravenous infusion, within 7 days prior to the first dose of study drug are excluded.
• •Poor blood pressure control (systolic blood pressure \>140 mmHg, diastolic blood pressure \>90 mmHg).
• •Active pulmonary tuberculosis. Active or uncontrolled infections requiring systemic treatment. Clinical active diverticulitis, intra-abdominal abscess, or gastrointestinal obstruction.
• •Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis.
• •Poorly controlled diabetes (fasting blood glucose \>10 mmol/L). Urine analysis showing urinary protein ≥++ and confirmed 24-hour urinary protein \>1.0 g.
• •Presence of psychiatric disorders that would hinder compliance with treatment.
• •19. Any medical history, evidence of disease, or abnormal laboratory values that could interfere with the study results, hinder the subject's full participation in the study, or pose other potential risks as determined by the investigator.