Tislelizumab（Anti PD-1), Lenvatinib and GEMOX Transformation in the Treatment of Potentially Resectable, Locally Advanced Biliary Tract Cancer

Inclusion Criteria:

• 1. Male or female aged 18-70 2. The patient must sign an informed consent form beforejoining the group, understand and be willing to sign a written informed consent form

3. Potentially resectable locally advanced BTC (including ICC, PBDT and GBC) confirmedby histology or cytology, agree to provide previously stored tumor tissue specimens orfresh biopsy tumor lesions for biomarker detection 4. Local progress, failure toachieve R0 resection, and no distant metastasis, with potential resection 5. At leastone measurable lesion (RECIST 1.1) 6. Have never received systemic treatment forbiliary tumors in the past 7. Eastern Cooperative Oncology Group (ECOG) performancestatus score ECOG PS 0-1 8. Liver function classification is Child-Pugh A 9. The bonemarrow, liver and kidneys are fully functional and reach the following clinicallaboratory evaluation standards within 7 days before treatment: Blood indicators: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L, platelet ≥ 90 × 109/L, hemoglobin ≥ 90 g/L. Liver function indicators: AST and ALT are both ≤3×ULN (upper limit of normal value); total bilirubin ≤1.5×ULN Kidney function indicators: Serum creatinine≤1.5×ULN Coagulation index: International normalized ratio (INR) ≤ 1.2 or prothrombin time (PT) ≤ 1.2×ULN Obstructive jaundice, after PTCD or ERCP treatment, if the liver function indicators meetthe requirements for entry, it can be considered for entry:
4. If the subject has HBV or HCV infection, the following conditions must be met: For inactive/asymptomatic carriers of HBV, chronic, or active HBV: HBV deoxyribonucleic acid (DNA) <2000 copies/mL during the screening period. Remarks:Patients with HBV DNA>2000 copies/mL should be treated according to treatment guidelines.Patients who received antiviral drug treatment at the time of screening should have HBV-DNA <2000 copies/mL and continue treatment during the study period. For subjects infected with HCV: If the infection is confirmed based on the detectable HCV ribonucleic acid RNA, suchsubjects cannot be included in the group.
5. If you are a fertile woman (that is, physically capable of getting pregnant), you mustagree to take effective contraceptive measures during the study period and within 120 daysafter the last administration, and have urine within 7 days before the first study drugadministration Or the serum pregnancy test is negative.
6. If you are a non-sterilized male, you need to agree to take effective contraceptivemeasures during the study period and 120 days after the last dose.
7. Life expectancy ≥ 3 months

Exclusion Criteria:

• 1. Diagnosed as mixed type of periampullary carcinoma, hepatocellular carcinoma andcholangiocarcinoma 2. Have received systemic treatment for biliary tumors in the past

3. Have previously received gemcitabine-based chemotherapy or TKI therapy or any tumorimmunotherapy (for example, PD-1/L1 inhibitors, CTLA-4 inhibitors, etc.) 4. Have ahistory of severe hypersensitivity to other monoclonal antibodies 5. Allergy totislelizumab or any of its excipients; allergy to oxaliplatin and any of itsexcipients; allergy to gemcitabine and any of its excipients; allergy to lenvatiniband any of its excipients 6. The presence of pericardial effusion, uncontrollablepleural effusion or clinically obvious ascites within 7 days before treatment isdefined as meeting the following criteria: (a) Ascites can be detected by physicalexamination during screening, or (b) during screening, Ascites requires puncturefluid.
4. There is no clinical evidence of portal hypertension with esophageal or gastricvarices within 6 months before starting treatment.
5. Any bleeding or thrombotic disease or any anticoagulant (such as warfarin orsimilar drugs) that needs to monitor the international standardized ratio duringtreatment within 6 months before the start of treatment 9. Has suffered from anymalignant tumors, except for the BTC studied in this clinical trial and locallyrecurring cancers that have been cured (such as resected basal cell or squamous cellskin cancer, superficial bladder cancer, cervical or breast cancer) Carcinoma in situ,occult carcinoma of the thyroid).
6. Any known central nervous system metastasis and/or leptomeningeal disease havebeen present before treatment.
7. A history of any active immunodeficiency or autoimmune disease and/or anyimmunodeficiency or autoimmune disease that may recur at the time of screening Note: Subjects with the following diseases can be selected: Type I diabetes Hypothyroidism (if only hormone replacement therapy can be used to control)Controlled celiac disease Skin diseases that do not require systemic treatment (egvitiligo, psoriasis, hair loss) Any other disease that will not recur without externaltriggers 12. Any disease requiring systemic treatment with corticosteroids (dose higherthan 10mg/day of prednisone or equivalent doses of similar drugs) or otherimmunosuppressive agents in the 14 days before treatment. Remarks: Subjects who have currently or previously used any of the following steroidregimens can be selected: In the absence of active autoimmune diseases, adrenaline replacement steroids are allowed (prednisone ≤10mg/day or equivalent dose of similar drugs) Local, ophthalmic,intra-articular, intranasal and inhaled corticosteroids with minimal systemic absorptionProphylactic short-term use (≤7 days) corticosteroids (for example, allergy to contrastagents) or for the treatment of non-autoimmune conditions (for example, delayedhypersensitivity reactions caused by contact allergens) 13. There is a history ofinterstitial lung disease or non-infectious pneumonia.
8. Any serious chronic infection or active infection (excluding viral hepatitis) thatrequires systemic antibacterial, antifungal or antiviral therapy (such as tuberculosis)before starting treatment.
9. The electrocardiogram during screening showed that the QT interval (QTc) correctedaccording to the heart rate (corrected according to the Fridericia method) exceeded 450msec. Note: If any patient finds that the QTc interval exceeds 450 msec during the first ECGexamination, the ECG will be repeated to confirm the result.
10. Any of the following cardiovascular risk factors: Cardiogenic chest pain in the 28 daysbefore treatment, defined as moderate pain that restricts daily activities (ADL)Symptomatic pulmonary embolism occurred within 28 days before treatment A history of acutemyocardial infarction occurred within 6 months before treatment. Any history of heart failure reaching New York Heart Association grade III or IV within 6months of treatment Ventricular arrhythmia of grade ≥2 occurred within 6 months beforetreatment Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within 6 months before treatment.
11. Have received organ transplantation or hematopoietic stem cell transplantation (HSCT)or any major surgery within 28 days before treatment.
12. Known mental or substance abuse disorders that may interfere with test compliance.
13. Live vaccine has been vaccinated 28 days before treatment. Note: Seasonal influenzavaccines are generally inactivated influenza vaccines and are allowed to be used.
14. Known history of human immunodeficiency virus infection (HIV) or syphilis infection.
15. The history or evidence of any disease, treatment, or laboratory abnormality that mayconfuse the test results, interfere with the participation of the subject during the entiretrial, or the main investigator believes that it does not meet the subject's best benefit.
16. Currently participating in and receiving treatment, or participating in orparticipating in other drug or device research within 4 weeks after the firstadministration of the research drug.
17. From the screening visit to 120 days after the last drug administration, pregnancy orbreastfeeding, or expectation of pregnancy or childbirth within the planned duration of thetrial.
18. The investigator judges that the compliance is not good, or there are other conditionsthat make the patients unsuitable to participate in this trial.
19. There are various medical contraindications that prevent the use of enhanced imaging (CT or MRI).
20. There are surgical contraindications, and the researchers believe that it is notsuitable for surgical patients.