A Study of Durvalumab With or Without Tremelimumab in Endometrial Cancer

Inclusion Criteria

• Subjects must have recurrent or persistent endometrial carcinoma (including: Endometrioid adenocarcinoma, serous adenocarcinoma, undifferentiated carcinoma, dedifferentiated carcinoma, clear cell adenocarcinoma, mixed epithelial carcinoma, adenocarcinoma not otherwise specified (N.O.S.), mucinous adenocarcinoma, squamous cell carcinoma, and transitional cell carcinoma) or endometrial carcinosarcoma). Histologic documentation of diagnosis of carcinoma is required. MSI-high patients will be identified based on immunohistochemistry or MSI testing of archival tumor specimens by department of pathology or via known mutations found in mismatch repair genes via the Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay through MSKCC IRB# 12-245.
• All patients must have measurable disease. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI.
• Patients must have at least one "target lesion" to be used to assess response on this protocol as defined by RECIST version 1.1. Tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
• Age ≥ 18 years and life expectancy of ≥ 12 weeks.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Resolution of (non-laboratory) adverse effects of recent surgery, radiotherapy, or chemotherapy to Grade ≤1 prior to first study treatment (with the exception of alopecia or neuropathy).
• Patients must have had one prior platinum-based chemotherapeutic regimen for management of endometrial carcinoma or carcinosarcoma. Initial treatment may include chemotherapy, chemotherapy and radiation therapy, and/or consolidation/maintenance 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 are not required to receive, three additional cytotoxic regimen for management of recurrent or persistent disease. Hormonal therapies will not count toward the prior regimen limit.
• Adequate normal organ and marrow function defined by the following laboratory results obtained within 14 days prior to first treatment:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L (> 1500 per mm^3)
• Platelet ≥ 100 x 10^9/L (>100, 000 per mm^3)
• Hemoglobin ≥ 9.0 g/dL
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). (Unless Gilbert's Syndrome,for which Bilirubin ≤ 3 x institutional upper limit of normal (ULN) without concurrent clinically significant liver disease)
• AST (SGOT)/ALT (SGPT) ≤ 3 x institutional upper limit of normal unless (ULN) unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine ≤ 1.5 x institutional upper limit of normal (ULN)
• Female subjects must either be of non-reproductive potential (ie, post-menopausal by history: ≥55 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
• Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Patients must have been enrolled, or agree to consent to the companion genomic profiling study MSKCC IRB# 12-245. Results must be available before starting treatment on protocol.
• Patients must have signed an approved informed cons