Chidamide Plus Sintilimab for Chemotherapy-refractory Advanced High-grade Neuroendocrine Neoplasm

Inclusion Criteria:

1. Age ≥ 18 years;
2. Histologically confirmed advanced and metastatic high-grade neuroendocrine neoplasm;
3. Receive ≤ 2 types of chemotherapy for high-grade neuroendocrine tumors and had tumor progression;
4. ECOG ≤ 2;
5. Have at least one measurable lesion according to RECIST version 1.1;
6. Absolute neutrophil count ≥ 1.5×109 / L, platelet count ≥ 100×109 / L, hemoglobin ≥ 90 g/L;
7. Provide tumor samples for pathological diagnosis and PD-L1 biomarker detection;
8. Have ability to sign a written informed consent.

Exclusion Criteria:

1. Small cell lung cancer;
2. Have surgery or trauma within 4 weeks before enrollment, or are expected to receive surgical treatment;
3. Previous use of HDAC inhibitors;
4. Previous use of PD-1/PD-L1/PD-L2/CTLA-4 inhibitors;
5. Allergy to related drug components;
6. Have a medical history of immune deficiency diseases, or organ transplantation;
7. Have active autoimmune diseases requiring treatment or a medical history of autoimmune diseases in the past 2 years;
8. Have uncontrolled or significant cardiovascular disease;
9. Abnormal liver function (total bilirubin \> 1.5×upper limit of normal); Transaminases (ALT/AST) \>2.5×upper limit of normal (\>5x upper limit of normal for patients with liver metastases), abnormal renal function (serum creatinine \> 1.5×upper limit of normal);
10. Pregnancy ;
11. Receive any live or live attenuated vaccine within 4 weeks before enrollment;
12. Have serious diseases that may endanger the safety of patients, or affect patients to complete the research;
13. Any serious mental or cognitive disorder;
14. Patients are currently enrolled in another drug clinical trial within 4 weeks prior to enrollment;
15. Any other condition which is inappropriate for the study in the opinion of the investigators.