Study of Induction PD-1 Blockade (Nivolumab) in Patients With Surgically Complete Resectable Mismatch Repair Deficient Endometrial Cancer (NIVEC)

Inclusion Criteria:

1. Explicit and voluntary consent to participation in the trial obtained by signing anddating a consent form that clearly and completely describes the purpose, potentialrisks, and other important issues related to the trial.

2. Sex: female

3. Age (at the time of informed consent): 20 years and older

4. Subjects with histologically-or cytologically-confirmed endometrial cancer orcarcinosarcoma(Mixed Mullerian Tumor)

5. Clinical stage: Stage I - IIIC2 and surgically completely resectable

6. No evidence of distant metastases

7. MMRd or MSI-H subtype (defined by either deficient/loss expression of mismatchrepair (MMR) proteins MLH1, PMS2, MSH2, MSH6 or microsatellite instability-high (MSI-H) by polymerase chain reaction assay for 5 microsatellite markers)

8. ECOG Performance Status Score 0 or 1

9. Patients with a life expectancy of at least 3 months

10. Patients whose latest laboratory data meet the below criteria within 7 days beforefirst dose. If the date of the laboratory tests at the time of enrollment is notwithin 7 days before the first dose of the investigational product, testing must berepeated within 7 days before the first dose of the investigational product, andthese latest laboratory tests must meet the following criteria. Of note, laboratorydata will not be valid if the patient has received a granulocyte colony-stimulatingfactor (G CSF) or blood transfusion within 14 days before testing.

• White blood cells ≥2,000/mm3 and neutrophils ≥1,500/mm3

• Platelets ≥100,000/mm3

• Hemoglobin ≥9.0 g/dL

• AST (GOT) and ALT (GPT) ≤3.0-fold the upper limit of normal (ULN) of the studysite (or ≤5.0-fold the ULN of the study site in patients with liver metastases)

• Total bilirubin ≤1.5-fold the ULN of the study site

• Creatinine ≤1.5-fold the ULN of the study site or creatinine clearance (eitherthe measured or estimated value using the Cockcroft-Gault equation) >45 mL/min

11. Women of childbearing potential (including women with chemical menopause or nomenstruation for other medical reasons)#1 must agree to use contraception#2 from thetime of informed consent until 5months or more after the last dose of theinvestigational product. Also, women must agree not to breastfeed from the time ofinformed consent until 5 months or more after the last dose of the investigationalproduct.

• Women of childbearing potential are defined as all women after the onset ofmenstruation who are not postmenopausal and have not been surgically sterilized (e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy).Post-menopause is defined as amenorrhea for ≥12 consecutive months withoutspecific reasons. Women using oral contraceptives, intrauterine devices, ormechanical contraception such as contraceptive barriers are regarded as havingchildbearing potential.

• The subject must consent to use any one of the following methods ofcontraception: a condom for the subject's partner (male), an intrauterinedevice (IUD) for female subjects, or skin implantation of a rod contraceptive (Implanon).

• Complete sexual abstinence is also acceptable: Sexual abstinence is consideredhighly effective only if it is defined as abstaining from sexual intercoursewith the opposite sex for the entire duration of the trial treatment-relatedrisks. The reliability of sexual abstinence in relation to the duration of thetrial needs to be evaluated, and sexual abstinence should be a preferred androutine lifestyle of the subjects.

Exclusion Criteria:

1. Patients with multiple primary cancers (with the exception of completely resectedbasal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ,intramucosal carcinoma, or superficial bladder cancer, or any other cancer that hasnot recurred for at least 5 years)

2. Patients with residual adverse effects of prior therapy or effects of surgery thatwould affect the safety evaluation of the investigational product in the opinion ofthe investigator or sub-investigator.

3. Patients with current or past history of severe hypersensitivity to any otherantibody products

4. Patients with concurrent autoimmune disease or history of chronic or recurrentautoimmune disease

5. Patients with a current or past history of interstitial lung disease or pulmonaryfibrosis diagnosed based on imaging or clinical findings. Patients with radiationpneumonitis may be randomized if the radiation pneumonitis has been confirmed asstable (beyond acute phase) without any concerns about recurrence.

6. Patients with concurrent diverticulitis or symptomatic gastrointestinal ulcerativedisease

7. Patients with pericardial fluid, pleural effusion, or ascites requiring treatment

8. Patients with uncontrollable, tumor-related pain

9. Patients who have experienced a transient ischemic attack, cerebrovascular accident,thrombosis, or thromboembolism (pulmonary arterial embolism or deep vein thrombosis)within 180 days before randomization

10. Patients with a history of uncontrollable or significant cardiovascular diseasemeeting any of the following criteria:

• Myocardial infarction within 180 days before randomization

• Uncontrollable angina pectoris within 180 days before randomization

• New York Heart Association (NYHA) Class III or IV congestive heart failure

• Uncontrollable hypertension despite appropriate treatment (e.g., systolic bloodpressure ≥150mmHg or diastolic blood pressure ≥ 90 mmHg lasting 24 hours ormore)

• Arrhythmia requiring treatment

11. Patients receiving or requiring anticoagulant therapy for a disease. Patientsreceiving antiplatelet therapy including low-dose aspirin may be enrolled.

12. Patients with uncontrollable diabetes mellitus

13. Patients with systemic infections requiring treatment

14. Patients who have received systemic corticosteroids (except for temporary use, e.g.,for examination or prophylaxis of allergic reactions) or immunosuppressants within 28 days before randomization

15. Patients who have received antineoplastic drugs (e.g., chemotherapy agents,molecular-targeted therapy agents, or immunotherapy agents) within 28 days beforerandomization

16. Patients who have undergone surgical adhesion of the pleura or pericardium within 28days before randomization

17. Patients who have undergone surgery under general anesthesia within 28 days beforerandomization

18. Patients who have undergone surgery involving local or topical anesthesia within 14days before randomization

19. Patients who have received radiotherapy within 28 days before randomization, orradiotherapy to bone metastases within 14 days before randomization

20. Patients who have received any radiopharmaceuticals (except for examination ordiagnostic use of radiopharmaceuticals) within 56 days before randomization

21. Patients with a positive test result for any of the following: HIV-1 antibody, HIV-2antibody, HTLV-1 antibody, HBs antigen, or HCV antibody

22. Patients with a negative HBs antigen test but a positive test result for either HBsantibody or HBc antibody with a detectable level of HBV-DNA

23. Women who are pregnant or breastfeeding, or possibly pregnant

24. Patients who have received any other unapproved drug (e.g., investigational use ofdrugs, unapproved combined formulations, or unapproved dosage forms) within 28 daysbefore randomization

25. Patients who have previously received Nivolumab, anti-PD-1 antibody, anti-PD-L1antibody, anti-PD L2 antibody, anti-CD137 antibody, anti-CTLA-4 antibody or othertherapeutic antibodies or pharmacotherapies for regulation of T-cells

26. Patients judged to be incapable of providing consent for reasons such as concurrentdementia

27. Other patients judged by the investigator or sub-investigator to be inappropriate assubjects of this study

28. Patient with current or past history of hypersensitivity to Nivolumab.

29. WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation.If the urine test is positive or cannot be confirmed as negative, a serum pregnancytest will be required.