Efficacy and Safety of Chidamide+Sintilimab+Bev as Second-Line Therapy in Advanced Extrapulmonary Neuroendocrine Carcinoma

Inclusion Criteria: 1. Histologically or cytologically confirmed locally advanced, unresectable, or metastatic extrapulmonary neuroendocrine carcinoma (NEC). 2. Failure of first-line standard systemic therapy, with documented disease progression during or after treatment by imaging or clinical evidence (e.g., cytology of new ascites or pleural effusion). Patients who discontinued first-line therapy due to intolerable toxicity are eligible. 3. At least one measurable lesion per RECIST version 1.1. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Able to provide written informed consent and comply with study visits and procedures. 6. Age ≥ 18 years and ≤ 75 years. 7. Life expectancy ≥ 12 weeks. 8. Women of childbearing potential and men with female partners of childbearing potential must use effective contraception throughout the treatment period and for 6 months after the last dose of study treatment. 9. Adequate organ and bone marrow function within 7 days before enrollment, without support treatments (blood products, growth factors, albumin) within 14 days before testing: absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count (PLT) ≥ 100 × 10⁹/L; hemoglobin (HGB) ≥ 9.0 g/dL; serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); ALT/AST ≤ 3.0 × ULN (no liver metastasis) or ≤ 5.0 × ULN (with liver metastasis); serum albumin ≥ 25 g/L; serum creatinine (Cr) ≤ 1.5 × ULN; urine protein \< 2+ or 24-hour urine protein \< 1 g if urine protein ≥ 2+; INR ≤ 1.5 × ULN and APTT ≤ 1.5 × ULN. Exclusion Criteria: 1. Prior exposure to any anti-angiogenic therapy or histone deacetylase (HDAC) inhibitor. 2. Received any investigational drug within 4 weeks before the first dose of study treatment. 3. Simultaneously participating in another interventional clinical study (observational or follow-up studies are allowed). 4. Received last dose of anti-tumor therapy (chemotherapy, targeted therapy, immunotherapy, embolization, etc.) within 3 weeks before first dose. 5. Received radiotherapy within 4 weeks before first dose. 6. Residual radiation-related toxicity (e.g., pneumonitis, hepatitis, enteritis) from prior radiotherapy \> 4 weeks before first dose, including symptomatic cases or those requiring corticosteroids. 7. Received systemic immunosuppressive drugs within 4 weeks before first dose, except topical/inhaled corticosteroids or physiological systemic corticosteroids (≤ 10 mg/day prednisone equivalent). 8. Received or plans to receive live attenuated vaccines within 4 weeks before first dose or during the study. 9. Underwent major surgery within 4 weeks before first dose, or has unhealed wounds, ulcers, or fractures. 10. Resolved toxicity from prior anti-tumor therapy not recovered to NCI CTCAE version 5.0 grade ≤ 1 (except alopecia or non-clinically significant laboratory abnormalities). 11. Known symptomatic central nervous system (CNS) metastases or carcinomatous meningitis. Patients with treated and stable CNS metastases for ≥ 4 weeks and neurological symptoms recovered to grade ≤ 1 are allowed. 12. Active autoimmune disease requiring systemic therapy within 2 years before first dose; or primary immunodeficiency. Replacement therapy (e.g., thyroid hormone, insulin) is permitted. 13. Active tuberculosis, or anti-tuberculosis treatment within 1 year before first dose. 14. Interstitial lung disease requiring corticosteroid treatment. 15. Active hepatitis B (HBsAg positive and HBV DNA ≥ 200 IU/mL) or active hepatitis C (HCV antibody positive and HCV RNA positive). 16. Known HIV infection or syphilis. 17. Severe uncontrolled active infection, including hospitalization for infection within 4 weeks before first dose. 18. Significant malnutrition requiring intravenous nutrition, unless corrected for \> 4 weeks before first dose. 19. Symptomatic congestive heart failure (NYHA class II-IV), or symptomatic/uncontrolled arrhythmia. 20. Uncontrolled arterial hypertension despite optimal treatment (systolic BP ≥ 150 mmHg or diastolic BP ≥ 100 mmHg). 21. Any arterial thromboembolic event (myocardial infarction, pulmonary embolism, unstable angina) within 6 months before enrollment. 22. History of deep vein thrombosis or other severe thromboembolism within 3 months before enrollment (catheter-related or superficial vein thrombosis excluded). 23. Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh B or C cirrhosis. 24. History of gastrointestinal perforation/fistula, peptic ulcer, bowel obstruction, extensive bowel resection, Crohn's disease, ulcerative colitis, intra-abdominal abscess, or chronic diarrhea within 6 months before enrollment; or intestinal stent placement. 25. Uncontrolled metabolic disorders or other severe medical conditions that may increase study risk or confound result interpretation. 26. Hereditary bleeding tendency or coagulation disorder. 27. Any life-threatening bleeding event within 3 months before enrollment (requiring transfusion, surgery, or continuous treatment). 28. High bleeding risk per investigator assessment: severe esophageal/gastric varices, intermittent bleeding (e.g., hematochezia, hemoptysis). 29. Cerebrovascular accident (including transient ischemic attack) within 6 months before enrollment. 30. Use of aspirin (\> 325 mg/day) or other platelet inhibitors for 10 consecutive days within 10 days before first dose. 31. Use of oral or parenteral anticoagulants or thrombolytics for 10 consecutive days within 10 days before first dose (prophylactic anticoagulation allowed). 32. Symptomatic or drainable pleural effusion, ascites, or pericardial effusion (only small asymptomatic effusions by imaging are allowed). 33. History of other primary malignancy, except: Malignancy in complete remission for ≥ 2 years without treatment during study；adequately treated non-melanoma skin cancer or carcinoma in situ with no evidence of recurrence. 34. History of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. 35. Known hypersensitivity to any monoclonal antibody component or study drug excipients. 36. Pregnant or breastfeeding female patients. 37. History of alcoholism or drug abuse. 38. Any other acute or chronic disease, psychiatric disorder, or laboratory abnormality that, in the investigator's opinion, increases study risk or interferes with result interpretation.