pReOperative Dostarlimab and Novel Therapies in EndOmetrial Cancer

1. Patient is at least 18 years of age.
2. Patient is able to provide informed consent and able to comply with treatment and follow up schedule.
3. Patients with surgically operable FIGO (2009) stage 3-4 endometrial cancer.
4. Must not have received any systemic anti-cancer treatment (including chemotherapy, hormonal therapy, immunotherapy, surgical intervention, radiotherapy) for the current diagnosis of endometrial cancer.
5. Histological diagnosis of advanced epithelial endometrial cancer (excluding carcinosarcoma).
6. CT or MRI proven disease (measurable or non-measurable).
7. Willing to provide tissue from archival diagnostic sample, a newly obtained core or excisional biopsy of a tumour lesion at screening and also collection of tissue during surgery.
8. Mismatch repair status must be known at time of enrolment. Patients can be screened based on local MMR/MSI testing results using immunohistochemistry (IHC), polymerase chain reaction (PCR), or next generation sequencing (NGS) performed in a certified local laboratory, i. MMR status must be assessed by immunohistochemistry (IHC) for MMR protein expression (MLH1, MSH2, MSH6, PMS2) where loss of one or more proteins indicates dMMR; dMMR may be determined locally.

   ii. MSI status as determined by polymerase chain reaction (PCR) or by tissue Next generation sequencing (NGS).

   Note: Patients who are known to have Lynch syndrome and have been found to carry a specific germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2) and have dMMR or MSI-H in the tumour are eligible to participate.
9. Patient must have a negative serum pregnancy test within 24 hours prior to the date of the first dose of trial medication; unless they are of non-childbearing potential.

   Non-childbearing potential is defined as:

   i. ≥ 45 years of age and has not had menses for \> 1 year. ii. Amenorrheic for \< 2 years without a hysterectomy and oophorectomy and have a follicle-stimulating hormone (FSH) value in the postmenopausal range upon pre-trial evaluation.
10. Patients should have adequate bone marrow and laboratory functions defined as:

    * Absolute neutrophil count (ANC) ≥1.5×109/L
    * Haemoglobin ≥9 g/dL ≥5.6 mmol/L
    * Platelets ≥100×109/L
    * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5×ULN
    * Bilirubin ≤1.5×ULN (isolated bilirubin \>1.5×ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%)
    * For patients not taking warfarin: International normalized ratio (INR) \<1.5 or prothrombin time (PT) \<1.5×ULN and partial thromboplastin (PTT) \<1.5×ULN. Patients taking warfarin may be included on a stable dose with a therapeutic INR \<3.5.
    * Renal function parameters of GFR ≥30 mL/min/1.73m2 (institutional creatinine ≤1.5×ULN)
    * Albumin \> 30
11. ECOG Performance Status 0 or 1.
12. Life expectancy of at least 3 months.