Envofolimab and Lenvatinib Combined With Gemcitabine Plus Cisplatin for Advanced BTC as First-Line Treatment(ENLIGHTEN)

This is a phase 2, single-arm, open label study. The purpose is to investigate both the efficacy and safety of Envofolimab and Lenvatinib in combination with Gemcitabine plus Cisplatin for treatment of advanced biliary tract cancer as first-line treatment.

The trial will recruit 43 patients. At the first step, 10 patients will be recruited. Only when at least 4 patients achieve objective response will the trial enter the second step and continue to recruit other patients. After being enrolled, all patients giving written informed consent will receive treatment until progression of disease, unacceptable toxicity or death. The tumor response evaluation will be conducted on a regular basis until progression of disease. Long-term survival follow up will be conducted as well.

Eligibility Criteria:
Inclusion Criteria:

1. Written informed consent obtained from the patient prior to treatment.
2. Age \> 18 years at the time of study entry.
3. Pathologically confirmed advanced biliary tract cancer, not having received systemic therapy.
4. Measurable or evaluable lesions according to RECIST v1.1 criteria.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
6. Life expectancy ≥ 12 weeks.
7. Adequate hematologic (absolute neutrophil count ≥ 1,500/μL, platelets count ≥ 100,000/μL, hemoglobin ≥ 9.0 g/dL), renal (serum creatinine ≤ 1.5 × upper limit of normal (ULN) or creatinine clearance ≥ 50 mL/min (Cockcroft-Gault), urinary protein \< 2+ or ≤ 1g/24h) and hepatic function (total serum bilirubin ≤ 1.5 ×ULN, serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 2.5 × ULN).
8. Normal coagulation function (INR ≤ 1.5 × ULN, APTT ≤ 1.5 × ULN, PT ≤ 1.5 × ULN), without active bleeding or thrombotic diseases.
9. Willingness and ability to comply with the protocol.

Exclusion Criteria:

1. Diagnosis of any second malignancy, except for adequately treated basal cell skin cancer or in situ carcinoma of the cervix uteri.
2. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
3. Previous treatment with Chinese herbal medicine or immunomodulators within 2 weeks, or radiotherapy treatment within 4 weeks prior to the first dose of administration.
4. Abnormal thyroid function.
5. Uncontrolled hypertension.
6. Uncontrolled cardiac disease, including but not limited to heart failure (NYHA class II-IV), unstable angina pectoris, myocardial infarction within 1 year or cardiac arrhythmia.
7. Active or prior documented autoimmune or inflammatory disorders.
8. Any immunosuppressants or systemic steroid therapy (\> 10 mg daily dose of prednisone or equivalent) within 2 weeks prior to enrollment.
9. Central nervous system metastases.
10. Active infection or unknown fever(\>38.5℃) prior to the first dose of administration, except for cancerous fever.
11. History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-associated pneumonia or severely impaired lung function.
12. Inherited or acquired immunodeficiency disease, including but not limited to infection of HIV or active hepatitis (HBV DNA ≥ 1000 IU/ml or HCV RNA ≥ 1000 IU/ml).
13. Live vaccine administration within 4 weeks prior to the first dose of administration or probably during the study.
14. History of psychotropic substance abuse, alcohol abuse, or drug use.
15. Pregnancy or lactation
16. Exclusion from the study by the judgement of investigator, due to some factors that may lead to the forced termination of the study.