Lenvatinib Combined With PD-1 Inhibitors as First-line Treatment for Unresectable/Advanced Biliary Tract Carcinoma

Lenvatinib Combined With PD-1 Inhibitors as First-line Treatment for Unresectable/Advanced Biliary Tract Carcinoma：a Multicenter,Single-arm,Phase II Study

This is a multi-center, single-arm,phase Ⅱ study to evaluate the efficacy and safety of Lenvatinib in combination with PD-1 inhibitors as first-line treatment in patients with unresectable advanced Biliary Tract Carcinoma (BTC)

Inclusion Criteria:

1. Patients had good compliance, understood the study procedure, and signed written informed consent

2. Eastern Cooperative Oncology Group (ECOG) Performance Status of 2, Patients cannot tolerate chemotherapy or refuse to receive chemotherapy for any reason.

3. Pathologically or cytologically confirmed biliary tract cancer

4. Patients who are advanced and/or unresectable after imaging and multidisciplinary consultation

5. Patients must have at least one measurable lesion as defined by RECIST 1.1

6. Survival expectation of 12 weeks or longer after beginning of study treatment

7. The major organs meeting the following criteria:

   Adequate bone marrow function,defined as: Hemoglobin (HGB) ≥80g/L;Neutrophil absolute count (ANC) ≥1.0×10^9/L;Platelet (PLT) ≥60×10^9/L

   Adequate liver function, defined as: aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 2.5× upper limit of normal (ULN) ( ≤ 5.0 × ULN for participants with the liver transplantion);Serum total bilirubin（STB） <1.5×ULN

   Adequate renal function ，defined as：Serum creatinine was within 1.5 times the normal range

8. Patients requiring biliary stent implantation must complete the procedure at least 14 days before enrollment

Exclusion Criteria:

1. Allergy to Lenvatinib or PD-1 inhibitors
2. Patients who have had other malignancies within the past 2 years (except cured carcinoma in situ and basal cell carcinoma of the skin)
3. Patients who have previously received systemic therapy, except for permitted neoadjuvant/adjuvant therapy, neoadjuvant/adjuvant therapy should be completed at least 4 months before diagnosis of advanced and/or unresectable disease
4. Patients with ampullary carcinoma are excluded (patients with mixed HCC/ BTC may be considered)
5. Active autoimmune disease requiring systemic treatment (i.e. corticosteroids or immunosuppressive drugs) within the past 2 years.Alternative therapies (e.g., thyroxine, insulin, or physical corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic and permitted
6. Major surgery prior to initiation of the study intervention and insufficient recovery from surgery and/or surgical complications
7. Radiation therapy was received within 2 weeks prior to initiation of study therapy. Or the subject must have recovered from all radiation-related toxicity, not required corticosteroids, and have not experienced radiation pneumonia; Palliative radiotherapy for non-central nervous system (CNS) disease (≤2 weeks) allows a washout period of 1 week (if deemed safe by the investigator)
8. Patients after organ transplantation
9. Known to have active tuberculosis (TB: tubercle bacilli)
10. Complete or incomplete intestinal obstruction
11. Have serious comorbidities that may affect study administration or evaluation of study results, such as HIV positive, active chronic HBV/HCV, clinically severe (i.e., active) heart disease, uncontrolled epilepsy, central nervous system disease, or psychiatric disorders;
12. Patients considered unsuitable for study judged by the researcher