Pembro/Carbo/Taxol in Endometrial Cancer

OUTLINE: This is a multi-center study. INVESTIGATIONAL TREATMENT: To ensure the safety of this combination treatment, an initial safety run-in will be conducted for the first 6 subjects. This initial cohort of 6 subjects will be enrolled and treated with standard doses as described below. Based on toxicity analysis of the initial 6 subjects following completion of 18 weeks of treatment, it will be determined if an extended safety run-in period would be beneficial. In the absence of receiving any prior therapy, eligible subjects will be treated as follows on D1 of cycles lasting 21 days (3 weeks) for a maximum of 6 cycles: * Pembrolizumab 200mg will be administered as a 30-minute intravenous (IV) infusion every 3 weeks. * Paclitaxel will be dosed at 175mg/m2 and be administered as a 3-hour continuous IV infusion. * Carboplatin will be dosed at area under the curve (AUC) of 6 and given as an IV infusion in 250ml of D5W over 30 minutes. Subjects who have had prior radiotherapy/platinum-based chemotherapy must initiate paclitaxel and carboplatin at the following reduced dose levels if they have had prior external radiotherapy involving the whole pelvis or abdomen or over 50% of their spine, and/or prior platinum-based chemotherapy for this, or any other cancer. Eligible subjects will be treated as follows on Day 1 (D1) of cycles lasting 21 days (3 weeks) for a maximum of 6 cycles: * Pembrolizumab 200mg administered as a 30-minute intravenous (IV) infusion every 3 weeks. * Paclitaxel will be dosed at 135mg/m2 and be administered as a 3-hour continuous IV infusion. * Carboplatin will be dosed at an AUC of 5 and given as an IV infusion in 250ml of D5W over 30 minutes. Subsequent doses of paclitaxel and carboplatin may be escalated to the higher doses as indicated above, provided these subjects do not exhibit hematologic or nonhematologic toxicity \> Grade 1, except alopecia. The following laboratory values must be obtained within 14 days prior to registration for protocol therapy: Hematopoietic: * Hemoglobin (Hgb) \> 9 g/dL (without transfusion or erythropoietin (EPO) dependency within 7 days of assessment) * Platelets \> 100 K/mm3 * Absolute neutrophil count (ANC) ≥ 1.5 K/mm3 Renal: * Creatinine or measured/calculated creatinine clearance (as calculated by institutional standard) ≤ 1.5 X institutional upper limits of normal (ULN) OR ≥60mL/min for subjects with creatinine levels \> 1.5 x institutional ULN Hepatic: * Serum total bilirubin ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN * Aspartate aminotransferase (AST), alanine transaminase (ALT) or alkaline phosphatase (ALP) \< 2.5 x ULN OR ≤ 5 x ULN for subjects with liver metastases * Albumin ≥ 2.5 mg/dL Coagulation (Blood Clotting) Tests: * International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants * Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless subject is receiving anti-coagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants