Clinical Efficacy Study of PD-1 Inhibitor Combined With Neoadjuvant Chemotherapy in Advanced Endometrial Cancer

Inclusion Criteria:

1. Endometrial cancer initially diagnosed as stage III non-operable resectable, stageIV (FIGO, 2009 criteria) after imaging evaluation

2. Pathologically confirmed endometrial cancer that looks like endometrial carcinoma

3. Patient age ≥18 years and ≤75 years old

4. ECOG status score of 0-1

5. tolerate surgery and radiotherapy

6. Laboratory tests: WBC ≥3.5×109/L, NEU ≥1.5×109/L, PLT ≥80×109/L, serum ≥80×109/L,serum ≥80×109/L, serum ≥80×109/L, serum ≥80×109/L.

×109/L, serum bilirubin ≤1.5 times the high limit of normal value, transaminase ≤1.5times the high limit of normal value, BUN ≤1.5 times the high limit of normal value.

1.5 times of the high limit of normal value, BUN, Cr≤normal value;

7. Able to follow up and good compliance;

8. Able to sign the informed consent form, including compliance with the requirementsand restrictions listed in the informed consent form and the program.

Exclusion Criteria:

1. Subjects with an active, known, or suspected autoimmune disease, or a history of anautoimmune disease, except for: vitiligo, alopecia areata, Graves' disease,psoriasis, or eczema that has not required systemic therapy within the last 2 years,hypothyroidism that is asymptomatic or requires only stable doses of hormonereplacement therapy (due to autoimmune thyroiditis), type 1 diabetes that requiresonly stable doses of insulin replacement therapy, asthma that subsides completely inchildhood and does not require intervention in adulthood, or diseases that do notrecur in the absence of external triggers;

2. Prior treatment with immune checkpoint inhibitors, including, but not limited to,other anti-PD-1, anti-PD-L1 antibodies, CTLA-4 antibodies, or any treatment directedagainst immune co-stimulators (e.g., antibodies directed against ICOS, CD40, CD137,GITR, OX40 targets, etc.) that target any mechanism of immune action against tumors;

3. Known hypersensitivity to any component and/or any excipient of the trial regimen;

4. Immunosuppressive drugs or systemic corticosteroids for immunosuppression (>10mg/day of prednisone or other equivalent) within 2 weeks prior to trial dosing;topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroids arepermitted;

5. Received herbs with antitumor effects or drugs with immunomodulatory effects (e.g.,thymidine, interferon, interleukin-2) within 2 weeks prior to the trial;

6. Active systemic infection requiring systemic treatment;

7. Serious infection within 4 weeks prior to the first dose, including but not limitedto complications requiring hospitalization, sepsis, or severe pneumonia;

8. Patients with untreated chronic hepatitis B, or HBV carriers with chronic hepatitisB virus (HBV) DNA greater than 1,000 IU/mL, or patients with active hepatitis C.Inactive HBsAg carriers, treated hepatitis B patients with stable disease (HBV DNA < 1000 IU/mL), and cured hepatitis C patients will be eligible for enrollment. HCVantibody-positive subjects will be eligible for the study only if they have anegative HCV RNA test;

9. Known active tuberculosis (TB), patients with suspected active TB should undergochest X-ray and sputum examination in conjunction with clinical signs and symptomsfor exclusion;

10. Immunodeficiency or human immunodeficiency virus (HIV antibody positive);

11. Subjects with active inflammatory bowel disease or a history of such disease (e.g.,Crohn's disease, ulcerative colitis, or chronic diarrhea). Subjects who are unableto swallow or who have malabsorption syndrome, uncontrolled nausea, vomiting,diarrhea, or other gastrointestinal disorders that severely interfere with drugintake and absorption;

12. Known interstitial lung disease that is symptomatic or may interfere with detectionor treatment of immune-associated pneumonia;

13. Treatment with a live or attenuated vaccine administered within 4 weeks prior to thefirst trial dose, inactivated seasonal influenza virus vaccine is permitted;

14. Patients who have received a prior allogeneic bone marrow transplant or solid organtransplant;

15. History of primary malignant tumor within the last 5 years;

16. Subjects who have undergone major surgery (e.g., open abdomen, open chest, organresection, etc.) and severe trauma within 28 days prior to the first dose ofimplantable infusion devices are permitted;

17. Subjects with a history of gastrointestinal perforation, gastrointestinal fistula,or female genital fistula;

18. Uncontrolled other co-morbidities, symptoms, or medical history, including: (1)Persons with one of the following cardiovascular diseases or cardiovascular riskfactors: myocardial infarction, unstable angina pectoris, pulmonary embolism,acute/continuous myocardial ischemia, cerebral vascular accident, transient ischemicattack, theor other clinically significant/required drug intervention arterial orvenous thrombosis, embolism or cerebral ischemic events; symptoms of congestiveheart failure (NYHA class III or higher) within 6 months (ii) clinically significantbleeding symptoms or a history of significant bleeding characteristics, such asgastrointestinal bleeding, gastric ulcer bleeding, or vasculitis, within 1 monthprior to the first dose; (iii) clinically active hemoptysis, active diverticulitis,abdominal abscess, and gastrointestinal obstruction; (iv) uncontrolled pleuraleffusion, pericardial effusion, or ascites requiring repeated drainage; (v)abnormalities of hepatic or renal development, or a history of surgery;

19. Female patients who are pregnant or breastfeeding; women of childbearing age whorefuse to accept contraceptive measures during neoadjuvant immunotherapy;

20. Concurrent participation in other interventional clinical trials; participation inobservational and non-interventional clinical trials is permitted;

21. Any condition that, in the opinion of the Investigator, may result in risk in thereceipt of the study drug or that would interfere with the evaluation of the safetyof the study drug or the interpretation of the study results. In the judgment of theInvestigator, it is unlikely that Patients who, in the judgment of the Investigator,are less likely to comply with the study steps, restrictions, and requirements shallnot be permitted to participate in this study.