Gemcitabine-Cisplatin Plus Envafolimab in Resectable Biliary Tract Malignancies (GENE)

Inclusion Criteria:

• Participants who have signed a written Informed Consent Form (ICF);
• Male or female participants aged 18-80 years;
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0/1;
• Biliary Tract Cancer (BTC) diagnosed by puncture pathology prior to enrollment;
• Participants must meet the following requirements for major vital organ function: a. Absolute neutrophil count (ANC) ≥ 1.5×10⁹/L; platelet count ≥ 90×10⁹/L; hemoglobin ≥ 9 g/dL; b. Coagulation function: international normalized ratio (INR) ≤ 1.2; c. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3 times the upper limit of normal (ULN); d. Serum albumin ≥ 3.5 g/dL; total bilirubin ≤ 1.5 times the ULN. Patients with obstructive jaundice who meet the eligibility criteria after percutaneous transhepatic cholangial drainage or endoscopic retrograde cholangiopancreatography treatment are also eligible for enrollment; e. Child-Pugh class A or B; f. Serum creatinine ≤ 1.5 times the ULN;
• Patients with high-risk factors for recurrence. The criteria are defined as meeting at least one of the following: a. Preoperative CA19-9 ≥ 200 U/mL; b. Tumor diameter ≥ 5 cm or multiple tumor nodules on imaging; c. Regional lymph node metastasis with a short-axis diameter ≥ 1.0 cm on imaging; d. Vascular invasion (portal vein or hepatic artery) on imaging; e. Low or undifferentiated histologic grade;
• Participants who have at least 1 measurable lesion (RECIST v1.1);
• Be able to provide fresh stool samples and liver samples if undergoing surgery.

Exclusion Criteria

• Pathological diagnosis of hepatocellular carcinoma, mixed hepatocellular carcinoma, and other non-cholangiocarcinoma malignant tumor components;
• Prior systemic therapy for BTC, including immunotherapy, targeted therapy, or chemotherapy;
• History of other prior or concurrent malignancies, except those with complete treatment and disease-free survival for more than 5 years;
• Presence of an active, known or suspected autoimmune disease, or requirement for long-term systemic corticosteroid therapy (equivalent to ≥ 10 mg prednisone daily) or other immunosuppressive agents. Participants using inhaled or topical corticosteroids will not be excluded;
• Presence of ascites, hepatic encephalopathy, sclerosing cholangitis, or other concurrent organ dysfunctions that would preclude tolerance of general anesthesia or hepatectomy;
• Women who are breastfeeding or pregnant;
• Any other factors that, in the investigator's judgment, may compromise participant safety or trial compliance, including serious comorbidities requiring ongoing treatment, clinically significant laboratory abnormalities, or relevant social or family-related issues.