Tisleizumab Combined With Lenvatinib and XELOX Regimen (Oxaliplatin Combined With Capecitabine) in the First-line Treatment of Advanced and Unresectable Biliary Tract Tumors

Inclusion Criteria:

• To be eligible to participate in this study, a patient must meet all of the followingcriteria:

1. Able to provide written informed consent and able to understand and agree tocomply with study requirements and assessment schedules
2. Histologically or cytologically confirmed unresectable or postoperative recurrentlocally advanced or metastatic biliary tract tumors, includingcholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer;
3. Aged 18-75 years old, male or female;
4. Eastern Cooperative Oncology Group (ECOG) fitness status score (PS score) 0-1;
5. Expected survival ≥ 3 months;
6. At least one measurable lesion according to RECIST V1.1;
7. No previous systemic therapy, including chemotherapy, targeted therapy,immunotherapy;
8. Adequate organ function as indicated by the following laboratory values ≤ 7 daysprior to the first dose of study drug: a. Patients must not have required a transfusion of blood product or growthfactor support within the 14 days before sample collection during the ScreeningPeriod and met all of the following criteria: i. Absolute neutrophil count（ANC）≥ 1.5 × 10^9/L ii. Platelets ≥ 75 × 10^9/L iii. Hemoglobin ≥ 90 g/L b. Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance > 50 μmol/L c. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 ×ULN; if there is a lesion in liver, ALT or AST ≤ 5 × ULN; d. Serum total bilirubin ≤ 1.5 × ULN; e. International normalized ratio (INR) ≤ 1.5 or prothrombin time (PT) ≤ 1.5 ×ULN f. Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN g. Cardiac Doppler ultrasound evaluation score (LVEF) ≥ 50%.
9. Patients with positive hepatitis B surface antigen (HBsAg) or previous history ofHBV infection must receive antiviral agents before the first dose of study drugand continue treatment during the study.
10. Females of childbearing potential must agree to practice highly effectivecontraception during the study and for ≥ 120 days after the last dose of studydrug and have a negative serum pregnancy test ≤ 7 days of the first study drugadministration
11. Nonsterilized male patients must agree to practice highly effective contraceptionfor the duration of the study and for ≥ 120 days after study drug administration
12. Good compliance and family agrees to cooperate with survival follow-up.

Exclusion Criteria:

• To be eligible to participate in this study, a patient cannot meet any of thefollowing exclusion criteria:

1. Any active malignancy ≤ 2 years prior to the first dose of study drug, except thespecific cancers evaluated in this study and any curatively treated locallyrecurrent cancer (eg, resected basal or squamous cell skin cancer, superficialbladder cancer, carcinoma in situ of the cervix or breast).
2. Participation in other clinical trials within four weeks prior to the first doseof study drug;
3. Patients with any evidence or history of bleeding diatheses regardless ofseverity; patients with any bleeding or bleeding event ≥ CTCAE grade 3 within 4weeks before the first dose; patients with gastrointestinal diseases such asunhealed wound, fracture, active gastric and duodenal ulcer, ulcerative colitisor active bleeding of unresected tumor, or other conditions that may causegastrointestinal bleeding and perforation judged by the investigator;
4. Patients with uncontrolled brain metastasis, spinal cord compression,carcinomatous meningitis or brain or leptomeningeal disease found by CT or MRIwithin 4 weeks before the first dose of study drug;
5. Patients with any severe and/or uncontrolled disease, including: a) patients withunsatisfactory blood pressure control (systolic blood pressure ≥ 150 mmHg ordiastolic blood pressure ≥ 90 mmHg); b) unstable angina pectoris, myocardialinfarction, ≥ grade 2 congestive heart failure, or arrhythmia requiring treatment (including QTc ≥ 480 ms) within 6 months before the first dose of study drug; c)severe chronic or active infection (including tuberculosis infection, etc.)requiring systemic antibacterial, antifungal or antiviral therapy within 14 daysbefore the first dose of study drug, Note: patients with viral hepatitis areallowed to receive antiviral therapy; d) positive HIV test; e) poor control ofdiabetes (fasting blood glucose ≥ CTCAE grade 2); f) urine routine indicatingurine protein ≥ 1 +, and confirmed 24-hour urine protein quantification > 1.0 g;
6. Patients with any active autoimmune disease or a history of autoimmune disease (such as, but not limited: autoimmune hepatitis, interstitial pneumonia,enteritis, vasculitis, nephritis; patients with asthma requiring medicalintervention with bronchodilators can not be included); patients with thefollowing are allowed: vitiligo, psoriasis, alopecia without systemic treatment,well-controlled type I diabetes, hypothyroidism after replacement therapy;
7. If HCV RNA is detectable, the presence of HCV infection is confirmed and suchpatients are not eligible;
8. Uncontrolled pleural effusion, pericardial effusion or peritoneal effusionrequiring frequent drainage or medical intervention (clinically significantrecurrence,requiring additional intervention within two weeks after intervention,excluding exfoliative cytology of exudates) within 7 days before the first doseof study drug;
9. Has any condition that required systemic treatment with corticosteroids (> 10mg/day prednisone or equivalent) or other immunosuppressive medications within 14days before the first dose of study drug.
10. Use of Chinese herbal medicines or Chinese patent medicines with antitumoractivity approved by the China National Medical Products Administration (NMPA),regardless of the type of cancer, within 14 days before the first dose of studydrug
11. Has been administered a live vaccine within 28 days prior to study drugadministration
12. Has a History of severe hypersensitivity reaction or any contraindication to anycomponent of the tislelizumab or lenvatinib formulation or any component of thecontainer;
13. Patients with concomitant diseases that seriously jeopardize the patient's safetyor affect the patient's completion of the study judged by the investigator;
14. Pregnant and lactating women;
15. Malabsorption syndrome or inability to take oral medications for other reasons.