Pembrolizumab in Ultramutated and Hypermutated Endometrial Cancer

Inclusion Criteria

• Patients must have histologically confirmed endometrial cancer that is recurrent or progressive following at least one prior chemotherapy regimen.
• Patients with the following histologic epithelial cell types are eligible: Endometrioid adenocarcinoma, serous adenocarcinoma, clear cell carcinoma, undifferentiated carcinoma, mixed epithelial carcinoma, carcinosarcoma, and adenocarcinoma not otherwise specified (N.O.S.).
• Tumors must demonstrate ultramutation (POLE/POLD1-mutation) and/or hyper-mutation (due to MMR gene defect) in a representative primary or metastatic tumor site by next generation sequencing (NGS) and Comprehensive Genomic Profiling (CGP) testing, and/or standard PCR-based DNA microsatellite instability (MSI) and immunohistochemistry (IHC).
• All patients must have measurable disease by RECIST 1.1.
• Patients must have a ECOG performance status of 0 or 1.
• Women of childbearing potential must have a negative urine and serum pregnancy test within 72 hours prior to receiving first dose and must be willing to use contraceptive through 120 days of last dose of Pembrolizumab.
• Patients must have recovered from effects of recent surgery, radiotherapy, or chemotherapy. Patients with ≥ Grade 2 neuropathy are eligible.
• Patients may have received prior radiation therapy for treatment of endometrial cancer. Prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy. All radiation therapy must be completed at least 4 weeks prior to the first date of study therapy.
• Patients may have received prior hormonal therapy for treatment of endometrial carcinoma. All hormonal therapy must be discontinued at least one week prior to the first date of study therapy.
• Patients may have received prior therapy (including chemotherapy, biologic/targeted therapy and immunotherapy) for treatment of endometrial cancer. All therapy must be discontinued at least 3 weeks prior to the first date of study therapy. Any investigational agent must be discontinued at least 30 days prior to the first date of study therapy.
• Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen.
• Patients are allowed to receive, but not required to receive, up to 4 additional lines of therapy.
• At least 4 weeks must have elapsed since the patient underwent any major surgery (e.g., major: laparotomy, laparoscopy) There is no delay in treatment for minor procedures (e.g., tumor FNA or core biopsy, venous access device placement).
• Have demonstrated adequate organ function. All screen labs should be performed within 14 days of treatment initiation
• Patients must have signed an approved informed consent and authorization permitting release of personal health information.
• Patients must be 18 years or older

Exclusion Criteria

• Patients who have had prior therapy with nivolumab, pembrolizumab or with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways.
• History of severe hypersensitivity reaction to any monoclonal antibody.
• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients who are pregnant or nursing. The effects of pembrolizumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP should use an adequate method to avoid pregnancy fo