| Eligibility |
Inclusion Criteria:
- 1. Male or female aged 18-70 2. The patient must sign an informed consent form before
joining the group, understand and be willing to sign a written informed consent form
3. Potentially resectable locally advanced BTC (including ICC, PBDT and GBC) confirmed
by histology or cytology, agree to provide previously stored tumor tissue specimens or
fresh biopsy tumor lesions for biomarker detection 4. Local progress, failure to
achieve R0 resection, and no distant metastasis, with potential resection 5. At least
one measurable lesion (RECIST 1.1) 6. Have never received systemic treatment for
biliary tumors in the past 7. Eastern Cooperative Oncology Group (ECOG) performance
status score ECOG PS 0-1 8. Liver function classification is Child-Pugh A 9. The bone
marrow, liver and kidneys are fully functional and reach the following clinical
laboratory 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 meet
the requirements for entry, it can be considered for entry:
10. 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, such
subjects cannot be included in the group.
11. If you are a fertile woman (that is, physically capable of getting pregnant), you must
agree to take effective contraceptive measures during the study period and within 120 days
after the last administration, and have urine within 7 days before the first study drug
administration Or the serum pregnancy test is negative.
12. If you are a non-sterilized male, you need to agree to take effective contraceptive
measures during the study period and 120 days after the last dose.
13. Life expectancy = 3 months
Exclusion Criteria:
- 1. Diagnosed as mixed type of periampullary carcinoma, hepatocellular carcinoma and
cholangiocarcinoma 2. Have received systemic treatment for biliary tumors in the past
3. Have previously received gemcitabine-based chemotherapy or TKI therapy or any tumor
immunotherapy (for example, PD-1/L1 inhibitors, CTLA-4 inhibitors, etc.) 4. Have a
history of severe hypersensitivity to other monoclonal antibodies 5. Allergy to
tislelizumab or any of its excipients; allergy to oxaliplatin and any of its
excipients; allergy to gemcitabine and any of its excipients; allergy to lenvatinib
and any of its excipients 6. The presence of pericardial effusion, uncontrollable
pleural effusion or clinically obvious ascites within 7 days before treatment is
defined as meeting the following criteria: (a) Ascites can be detected by physical
examination during screening, or (b) during screening, Ascites requires puncture
fluid.
7. There is no clinical evidence of portal hypertension with esophageal or gastric
varices within 6 months before starting treatment.
8. Any bleeding or thrombotic disease or any anticoagulant (such as warfarin or
similar drugs) that needs to monitor the international standardized ratio during
treatment within 6 months before the start of treatment 9. Has suffered from any
malignant tumors, except for the BTC studied in this clinical trial and locally
recurring cancers that have been cured (such as resected basal cell or squamous cell
skin cancer, superficial bladder cancer, cervical or breast cancer) Carcinoma in situ,
occult carcinoma of the thyroid).
10. Any known central nervous system metastasis and/or leptomeningeal disease have
been present before treatment.
11. A history of any active immunodeficiency or autoimmune disease and/or any
immunodeficiency 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 (eg
vitiligo, psoriasis, hair loss) Any other disease that will not recur without external
triggers 12. Any disease requiring systemic treatment with corticosteroids (dose higher
than 10mg/day of prednisone or equivalent doses of similar drugs) or other
immunosuppressive agents in the 14 days before treatment.
Remarks: Subjects who have currently or previously used any of the following steroid
regimens 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 absorption
Prophylactic short-term use (=7 days) corticosteroids (for example, allergy to contrast
agents) or for the treatment of non-autoimmune conditions (for example, delayed
hypersensitivity reactions caused by contact allergens) 13. There is a history of
interstitial lung disease or non-infectious pneumonia.
14. Any serious chronic infection or active infection (excluding viral hepatitis) that
requires systemic antibacterial, antifungal or antiviral therapy (such as tuberculosis)
before starting treatment.
15. The electrocardiogram during screening showed that the QT interval (QTc) corrected
according to the heart rate (corrected according to the Fridericia method) exceeded 450
msec.
Note: If any patient finds that the QTc interval exceeds 450 msec during the first ECG
examination, the ECG will be repeated to confirm the result.
16. Any of the following cardiovascular risk factors: Cardiogenic chest pain in the 28 days
before treatment, defined as moderate pain that restricts daily activities (ADL)
Symptomatic pulmonary embolism occurred within 28 days before treatment A history of acute
myocardial infarction occurred within 6 months before treatment.
Any history of heart failure reaching New York Heart Association grade III or IV within 6
months of treatment Ventricular arrhythmia of grade =2 occurred within 6 months before
treatment Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within
6 months before treatment.
17. Have received organ transplantation or hematopoietic stem cell transplantation (HSCT)
or any major surgery within 28 days before treatment.
18. Known mental or substance abuse disorders that may interfere with test compliance.
19. Live vaccine has been vaccinated 28 days before treatment. Note: Seasonal influenza
vaccines are generally inactivated influenza vaccines and are allowed to be used.
20. Known history of human immunodeficiency virus infection (HIV) or syphilis infection.
21. The history or evidence of any disease, treatment, or laboratory abnormality that may
confuse the test results, interfere with the participation of the subject during the entire
trial, or the main investigator believes that it does not meet the subject's best benefit.
22. Currently participating in and receiving treatment, or participating in or
participating in other drug or device research within 4 weeks after the first
administration of the research drug.
23. From the screening visit to 120 days after the last drug administration, pregnancy or
breastfeeding, or expectation of pregnancy or childbirth within the planned duration of the
trial.
24. The investigator judges that the compliance is not good, or there are other conditions
that make the patients unsuitable to participate in this trial.
25. There are various medical contraindications that prevent the use of enhanced imaging
(CT or MRI).
26. There are surgical contraindications, and the researchers believe that it is not
suitable for surgical patients.
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