TC Plus PD-1 Inhibitors Combined With Anlotinib for Advanced Advanced Esophageal Cancer

Inclusion Criteria: 1. Patients volunteered to participate in the study and signed the informed consent; 2. Age 18-75, both male and female; 3. Histologically or cytologically confirmed advanced or metastatic (stage IIIB, III C or IV) ESCC . 4. At least one measurable lesion according to RECIST 1.1,which should not be treated locally, such as radiotherapy. 5. ECOG PS 0-1- Page 3 of 5 \[DRAFT\] - 6. Expected survival ≥ 3 months 7. Patients who never received systemic therapy in the past, including radiotherapy ,chemotherapy, targeted therapy and immunotherapy , or patients who relapsed more than 6 months after adjuvant chemotherapy. 8. The main organ functions accorded with the following criteria within 7 days before treatment: (1)Blood routine examination ( without blood transfusion in 14 days): hemoglobin (HB) ≥ 90 g/L; neutrophil absolute value (ANC) ≥ 1.5 \*109/L; platelet (PLT) ≥80 \*109/L. (2) Biochemical tests should meet the following criteria: 1) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); 2) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 \*ULN, if accompanied by liver metastasis, ALT and AST ≤ 5\* ULN; 3) serum creatinine (Cr) ≤ 1.5\* ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;4) Serum albumin (≥35g/L). (3) Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥the low limit of normal value (50%). 9 Tissue samples should be provided for biomarker analysis (such as PD-L1 ) Patients who could not provide new tissues could provide 5-8 paraffin sections of 3-5 μm by archival preservation. Exclusion Criteria: 1. Severe allergic reactions to humanized antibodies or fusion proteins in the past 2. known to have hypersensitivity to any component contained in Endostar or antibody preparations; 3. Diagnosed of immunodeficiency or received systemic glucocorticoid therapy or any other form of immunosuppressive therapy within 14 days before the study, allowing physiological doses of glucocorticoids (≤10mg/day prednisone or equivalent); 4. Patients with active, known or suspected autoimmune diseases. Patients with type I diabetes, hypothyroidism requiring hormone replacement therapy, skin disorders requiring no systemic treatment(such as vitiligo, psoriasis or alopecia). Patients who would not triggers can be included. 5. Serious heart disease, include congestive heart failure, uncontrollable high-risk arrhythmia, unstable angina pectoris, myocardial infarction, and severe valvular disease. 6. Patients treated targeted drugs such as bevacizumab, sunitinib, sorafenib, imatinib, famitinib, regiffenil, apatinib and anlotinib 7. Patients recieved systemic antineoplastic therapy, including cytotoxic therapy, signal transduction inhibitors, immunotherapy (or mitomycin C within 6 weeks before the grouping),recieved over-extended-field radiotherapy (EF-RT) within 4 weeks before the grouping or limited-field radiotherapy to evaluate the tumor lesions within 2 weeks before the grouping 8. Positive hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus antibody (HCV Ab), indicating acute or chronic infection. 9. Patients with active pulmonary tuberculosis (TB) infection judged by chest X-ray examination, sputum examination and clinical physical examination. Patients with active pulmonary tuberculosis infection in the previous year should be excluded even if they have been treated; Patients with active pulmonary tuberculosis infection more than a year ago should also be excluded unless the course and type of antituberculosis treatment previously were appropriate. 10. Patients with brain metastases with symptoms or symptoms controlling less than 2 months