Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer

Exclusion Criteria

• •1. Endometrial carcinosarcoma or sarcoma;
• •2. Known MMR(mismatch repair)/MSI status with dMMR(deficient mismatch repair) or MSI-H(microsatellite instability-high);
• •3. Toxicities related to prior anticancer therapy did not recover to ≤CTCAE Grade 1, except alopecia and oxaliplatin-induced peripheral neurotoxicity ≤CTCAE Grade 2;
• •4. Received systemic anti-tumor therapy approved within 4 weeks before randomization;
• •5. Other malignancies within the past 5 years;
• •6. Previous or screening central nervous system (CNS) metastases;
• •7. Radical radiotherapy within 4 weeks before randomization
• •8. Previously received any anti-programmed cell death receptor-1 (PD-1) antibody, anti-PD-L1(programmed death ligand-1) antibody, anti-PD-L2(programmed death ligand-2) antibody, or anti cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody or any other antibody acting on T cell costimulation or checkpoint pathways (eg, OX40, CD137, etc) or small molecule vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors;
• •9. Symptomatic or treatment-requiring thyroid dysfunction at screening;
• •10. Use of immunosuppressive agents within 4 weeks before randomization
• •11. Presence of any active autoimmune disease requiring systemic treatment or history of autoimmune disease within the past 2 years;
• •12. Systemic immunostimulants within 4 weeks before randomization;
• •13. Administration of any live or live-attenuated vaccine within 4 weeks before randomization or planned during the study;
• •14. Major surgical procedures within 4 weeks before randomization;
• •15. Uncontrolled malignant pleural effusion, ascites or pericardial effusion;
• •16. Patients with current hypertension uncontrolled by medication;
• •17. Patients with any current disease or condition affecting drug absorption, or patients unable to take oral medications;
• •18. Receiving strong inducers of cytochrome P450 3A4 enzyme;
• •19. Patients with gastrointestinal diseases or unresected tumors with active bleeding, or other conditions that may cause gastrointestinal bleeding and perforation as judged by the investigator; or with gastrointestinal perforation or gastrointestinal fistula, which is not recovered after surgical treatment;
• •20. Active bleeding within 3 weeks before randomization, or melena, or bleeding from a tumor within 2 weeks before the first dose ;
• •21. Tumor invading major vascular structures and is judged by the investigator to be at greater risk of massive haemorrhage;
• •22. Patients who had arterial thrombosis or deep venous thrombosis within 6 months before randomization; or patients who had stroke events and/or transient ischemic attack within 12 months; patients who had thrombosis caused by implantable intravenous infusion pump or catheter, except patients who had stable thrombosis after conventional anticoagulant therapy;
• •23. Clinically significant cardiovascular disease;
• •24. Clinically significant electrolyte abnormalities as judged by the investigator;
• •25. Active infection or fever of unknown origin before randomization;
• •26. Patients with active pulmonary tuberculosis (TB) receiving anti-tuberculosis treatment or anti-tuberculosis treatment within 1 year before randomization;
• •27. Patients with previous and current history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired pulmonary function, which may interfere with the detection and management of suspected drug-related pulmonary toxicity; previous or current (non-infectious) pulmonary inflammation requiring steroid hormone therapy;
• •28. Positive human immunodeficiency virus (HIV) antibody screening;
• •29. Known history of clinically significant liver disease
• •30. Known hypersensitivity to any of the study drugs or any of their excipients, or previous history of serious hypersensitivity to any other monoclonal antibody;
• •31. Patients who have received other clinical drugs that have not been approved or marketed within 4 weeks before randomization;
• •32. Women who are pregnant (positive pregnancy test before medication) or breastfeeding;
• •33. Patients who have received tissue/organ transplantation;
• •34. Patients with known psychiatric disorders or substance abuse disorders that could affect study compliance;
• •35. Patients who, in the opinion of the investigator, have other reasons that would make them inappropriate for this clinical study.