Tucidinostat Plus PD-1 Inhibitor and Bevacizumab for Advanced Esophagus Cancer, AEG, Gastric Cancer

Inclusion Criteria:

1. Age ≥18 years, ≤ 75 years
2. Histologically or cytologically confirmed Esophageal squamous cell cancer, adenocarcinoma of esophagogastric junction and Gastric adenocarcinoma, unresectable, recurrent or metastatic disease.
3. Can provide at least 5 pieces of pathological section or fresh tumor tissue
4. Eastern Collaborative Oncology Group (ECOG) ≤ 1.
5. ≤2 systemic chemotherapy for advanced disease (total number of treatment lines for advanced disease ≤4).
6. Patients who have previously used PD-1 antibodies, PD-L1 antibodies, PD-L2 antibodies, or CTLA-4 antibodies (or any other antibodies acting on T cell co-stimulation or checkpoint pathways) or require a duration of ≥16 weeks;
7. Adequate organ function.
8. Life expectancy is more than 3 months.
9. For females of child bearing potential, a negative urine or serum pregnancy test result within 3 days before study treatment.
10. Willing and able to provide written informed consent.

Exclusion Criteria:

1. Allergies to any monoclonal antibody or Tucidinostat preparation have been known, and hypersensitivity reactions of more than 3 levels have occurred
2. Previously received immunotherapy and had grade 3 or above immune-related adverse events.
3. Previously received histone deacetylase inhibitors,or toripalimab, or angiogenesis inhibitors.
4. Subjects with any active, known or suspected autoimmune disease or history of autoimmune disease.
5. Known active CNS metastases and/or carcinomatous meningitis.
6. Received a live vaccine within 4 weeks of the first dose of study medication.
7. Major surgery received or severe traumatic injury, fracture, or ulcer occurred within 4 weeks of the first dose of study medication.
8. Pregnant or lactating female.
9. Uncontrolled clinically significant systemic diseases, including active infection, unstable angina, angina occurred within 3 months,≥ NYHA II congestive heart failure, myocardial infarction occurred within 6 months, severe arrhythmia, liver, kidney, or metabolic disease.
10. Participate in other clinical trials currently or within 4 weeks prior to enrollment.