• Number of patients who experience Adverse Events after one dose of Pembrolizumab [ Time Frame: 3 weeks ]
  The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
• Change in number of Tumor Infiltrating Lymphocytes by endometrial cancer sub-types [ Time Frame: 3 weeks ]
  Count and compare associations of (1) pre-treatment Tumor Infiltrating Lymphocyte (TIL) numbers (2) clonality of TILs and (3) change in number and phenotype of TILs with pembrolizumab treatment between Microsatellite Instability (MSI) and DNA Polymerase ε Endometrial Cancers (EC) versus MSI low/stable ECs versus Copy Number High ECs.
• Correlation of Programmed Cell Death-1 (PD-1) Expression with TILs [ Time Frame: 3 weeks ]
  Compare possible associations of PD-1, Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) messenger Ribonucleic Acid (mRNA) expression with (1) pre-treatment TIL numbers (2) clonality of TILs and (3) change in number and phenotype of TILs.
• Correlation of Immune and Obesity/Inflammation EC Signatures with TILs [ Time Frame: 3 weeks ]
  Compare possible associations of immune and obesity/inflammation EC signatures with (1) Body Mass Index (BMI) (2) pre-treatment TIL numbers (3) clonality of TILs and (4) change in number and phenotype of TILs.
• Correlation of Microbiota Profiles with TILs [ Time Frame: 3 weeks ]
  Compare possible associations of gut, vaginal and uterine microbiota profiles with (1) BMI (2) pre-treatment TIL numbers (3) clonality of TILs and (4) change in number and phenotype of TILs.
• Overall Response Rate of Pembrolizumab with Paclitaxel and Carboplatin [ Time Frame: 3 weeks ]
  Calculate the overall response rate of pembrolizumab in combination with paclitaxel and carboplatin following hysterectomy and surgical staging in (1) stage I/II, serous/clear cell EC and (2) stage III, Grade 3 (serous, clear cell or endometrioid histologies) EC. Response is measured as: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis <10mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

• Number of patients who experience Adverse Events after one dose of Pembrolizumab [ Time Frame: 3 weeks ]
  The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
• Change in number of Tumor Infiltrating Lymphocytes by endometrial cancer sub-types [ Time Frame: 3 weeks ]
  To assess possible associations of (1) pre-treatment Tumor Infiltrating Lymphocyte (TIL) numbers (2) clonality of TILs and (3) change in number and phenotype of TILs with pembrolizumab treatment between Microsatellite Instability (MSI) and DNA Polymerase ε Endometrial Cancers (EC) versus MSI low/stable ECs versus Copy Number High ECs.
• Correlation of Programmed Cell Death-1 (PD-1) Expression with TILs [ Time Frame: 3 weeks ]
  To investigate possible associations of PD-1, Programmed Death Ligand 1 (PD-L1) and Programmed Death Ligand 2 (PD-L2) messenger Ribonucleic Acid (mRNA) expression with (1) pre-treatment TIL numbers (2) clonality of TILs and (3) change in number and phenotype of TILs.
• Correlation of Immune and Obesity/Inflammation EC Signatures with TILs [ Time Frame: 3 weeks ]
  To investigate possible associations of immune and obesity/inflammation EC signatures with (1) Body Mass Index (BMI) (2) pre-treatment TIL numbers (3) clonality of TILs and (4) change in number and phenotype of TILs.
• Correlation of Microbiota Profiles with TILs [ Time Frame: 3 weeks ]
  To evaluate possible associations of gut, vaginal and uterine microbiota profiles with (1) BMI (2) pre-treatment TIL numbers (3) clonality of TILs and (4) change in number and phenotype of TILs.
• Overall Response Rate of Pembrolizumab with Paclitaxel and Carboplatin [ Time Frame: 3 weeks ]
  To estimate the overall response rate of pembrolizumab in combination with paclitaxel and carboplatin following hysterectomy and surgical staging in (1) stage I/II, serous/clear cell EC and (2) stage III, Grade 3 (serous, clear cell or endometrioid histologies) EC. Response is measured as: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis <10mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

• Endometrial Cancer
• Uterine Cancer

• Drug: Pembrolizumab

  A single dose of Pembrolizumab (200 mg) will be administered IV over 30 min (-5 /+10 min) approximately 3 weeks prior to the scheduled hysterectomy.

  Pembrolizumab (200 mg) will be administered IV over 30 min (-5/+10 min) every three weeks in combination with paclitaxel and carboplatin as adjuvant therapy over 6 cycles. Pembrolizumab should be given on D1 of each cycle after the infusion of cytotoxics.

  Other Name: Keytruda
• Procedure: Hysterectomy
  Hysterectomy/Surgical Staging per institutional standard of care.

Inclusion Criteria:

• Age ≥ 18 years at the time of consent.
• ECOG Performance Status of ≤ 1 (See Appendix 11.4).
• Diagnosis of histologically confirmed FIGO stage 1, grade 3, endometrioid, serous or clear cell cancer of the uterus.
• A medically appropriate candidate for hysterectomy and surgical staging as determined by an attending gynecologic oncologist.
• Has received no prior therapy for uterine cancer.
• Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 72 hours prior to initiating study treatment.

• A female participant is eligible to participate if she is not pregnant not breastfeeding, and at least one of the following conditions applies:

  1. Not a woman of childbearing potential (WOCBP)
  2. A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Have an available endometrial biopsy for correlative studies and willing to undergo a research biopsy prior to initiating study treatment. The research biopsy procedure must be deemed medically safe by the investigator.
• Subjects is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.

Exclusion Criteria:

• Active infection requiring systemic therapy.
• Pregnant or breastfeeding
• Has received a live vaccine within 30 days prior to the first dose of study drug.

Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Subject is receiving prohibited medications or treatments that cannot be discontinued/replaced by an alternative therapy.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a known history of Human Immunodeficiency Virus (HIV). Note: No HIV testing is required unless mandated by local health authority.
• Has a known history of Hepatitis B (defined as Hepatitis B surface antigen; HBsAg reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Has a history of symptomatic congestive heart failure (e.g. congestive heart failure defined as New York Heart Association (NYHA) Class III or IV functional status), unstable angina pectoris or cardiac arrhythmia.