Study of Fruquintinib Plus Sintilimab for Treatment of Advanced Endometrial Cancer

Inclusion Criteria:

1. Have fully understood and voluntarily signed the informed consent form

2. Age 18 to 75 years (inclusive) ; Body mass index (BMI) ≥ 18.5kg/m^2;

3. Histologically or cytologically confirmed advanced or recurrent endometrial cancerwith measurable lesions

4. Patients who previously failed first-line systemic platinum-based therapy

5. ECOG PS (Eastern Cooperative Oncology Group performance status score) 0 or 1;

6. Need to provide tumor samples for central lab testing of biomarkers such asMSI(microsatellite instability) status;

7. Non-MSI-H(non-microsatellite instability-high) by central lab or previous testresult indicating pMMR(proficient mismatch repair);

8. Adequate function of the major organs;

9. Expected survival ≥ 12 weeks;

10. Female patients of childbearing potential must have a negative serum pregnancy testwithin 7 days before randomization.

Exclusion Criteria:

1. Endometrial carcinosarcoma or sarcoma;

2. Known MMR(mismatch repair)/MSI status with dMMR(deficient mismatch repair) orMSI-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 deathligand-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 ofautoimmune 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 beforerandomization 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, orpatients 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 asjudged by the investigator; or with gastrointestinal perforation or gastrointestinalfistula, which is not recovered after surgical treatment;

20. Active bleeding within 3 weeks before randomization, or melena, or bleeding from atumor within 2 weeks before the first dose ;

21. Tumor invading major vascular structures and is judged by the investigator to be atgreater risk of massive haemorrhage;

22. Patients who had arterial thrombosis or deep venous thrombosis within 6 monthsbefore randomization; or patients who had stroke events and/or transient ischemicattack within 12 months; patients who had thrombosis caused by implantableintravenous infusion pump or catheter, except patients who had stable thrombosisafter 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-tuberculosistreatment or anti-tuberculosis treatment within 1 year before randomization;

27. Patients with previous and current history of pulmonary fibrosis, interstitialpneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severelyimpaired pulmonary function, which may interfere with the detection and managementof 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, orprevious history of serious hypersensitivity to any other monoclonal antibody;

31. Patients who have received other clinical drugs that have not been approved ormarketed 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 couldaffect study compliance;

35. Patients who, in the opinion of the investigator, have other reasons that would makethem inappropriate for this clinical study.