Window of Opportunity Pilot Study of Pembrolizumab in Obesity-driven Endometrial Cancer

Inclusion Criteria:

* Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
* Female Age ≥ 18 years at the time of consent.
* ECOG Performance Status of ≤ 1 (See Appendix 11.4).
* Diagnosis of advanced stage and histologically confirmed endometrioid, serous, clear cell, carcinosarcoma (including mixed) cancer of the uterus in which neoadjuvant chemotherapy is planned.
* Has received no prior therapy for uterine cancer, including hysterectomy
* 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.
* 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.