Bevacizumab Plus Nab-paclitaxel and Tegafur Gimeracil Oteracil Potassium Capsule (S-1) as Second-line Treatment for Advanced Biliary Tract Cancer: a Phase Ⅱ Clinical Trial

Inclusion Criteria:

• Aged ≥18 years at the time of signing the informed consent form (ICF).
• Histologically confirmed or clinically diagnosed biliary tract adenocarcinoma.
• Unresectable disease and not suitable for locoregional therapy, or disease progression after locoregional therapy.
• Child-Pugh class A or class B with a score of 7.
• Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1.
• Radiographic disease progression or intolerance after first-line treatment.

• Adequate bone marrow, hepatic, and renal function, as defined by:

  1. Absolute neutrophil count (ANC) ≥1.5 × 10^9/L, platelet count ≥75 × 10^9/L, and hemoglobin ≥85 g/L;
  2. Serum total bilirubin ≤1.5 × the upper limit of normal (ULN);
  3. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN;
  4. Estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m²;
  5. International normalized ratio (INR) ≤1.5 or prothrombin time (PT) ≤1.5 × ULN;
  6. Activated partial thromboplastin time (aPTT) ≤1.5 × ULN.
• For patients with hepatitis B virus (HBV) infection, HBV deoxyribonucleic acid (DNA) <500 IU/mL (or <2,500 copies/mL).
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Women of childbearing potential must use highly effective contraception during the study and for at least 120 days after the last dose of study treatment and must have a negative urine or serum pregnancy test within 7 days before the first dose of study treatment. Non-sterilized male participants must agree to use highly effective contraception during the study and for at least 120 days after the last dose of study treatment.

Exclusion Criteria:

• Histologically or cytologically confirmed fibrolamellar, sarcomatoid, or mixed cholangiocarcinoma.
• Active autoimmune disease or a history of autoimmune disease with the potential for recurrence.
• Any condition requiring systemic treatment with corticosteroids at a dose of >10 mg/day of prednisone or equivalent, or other immunosuppressive agents, within 14 days before the first dose of study treatment.
• Inadequately controlled hypertension despite medical therapy, defined as systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg.
• Active gastrointestinal disorders, including active gastric or duodenal ulcer or ulcerative colitis; active bleeding from an unresected tumor; or any other condition considered by the investigator to pose a risk of gastrointestinal bleeding or perforation. Patients with a history of gastrointestinal perforation or gastrointestinal fistula that had not healed after surgical treatment were also excluded.
• A history of arterial thrombosis or deep vein thrombosis within 6 months before enrollment, or evidence or a history of bleeding tendency within 2 months before enrollment, regardless of severity.
• Any clinical or laboratory abnormality or compliance issue that, in the investigator's judgment, made the participant unsuitable for participation in the study.