A Study of Pembrolizumab and Olaparib in People With Endometrial Cancer or Endometrial Carcinosarcoma

Exclusion Criteria

• •Patients must have had at least one but no more than three prior regimens for management of endometrial carcinoma (including neoadjuvant/adjuvant chemotherapy).
• •Patients must have had at least one but no more than three prior regimens for management of endometrial carcinoma (including neoadjuvant/adjuvant chemotherapy).
• •* Chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen.
• •* All chemotherapy must have been completed at least 3 weeks prior to the start of study therapy.
• •* Hormonal Therapy will NOT count as prior treatment line.
• •* All hormonal therapy for treatment of endometrial cancer must be discontinued at least one week prior to start of study therapy.
• •Have measurable disease based on RECIST 1.1.
• •Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• •Have adequate laboratory values as defined in the following table:
• •°Hematologic
• •Absolute neutrophil count (ANC) ≥1500/μL
• •Hemoglobin ≥10.0 g/dL
• •°Renal
• •Creatinine clearance (CrCL) or estimated Glomerular filtration rate (GFR) CrCL of ≥51 mL/minute estimated using either the Cockcroft-Gault equation, a 24 hour urine test or another validated test as per local practice (e.g., estimated GFR). Estimated CrCL =(140-age \[years\]) × weight (kg) × 0.85 (140-age \[years\]) × weight (kg) × 0.85 serum creatinine (mg/dL) × 72
• •°Hepatic
• •Total bilirubin ≤1.5 ×ULN (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
• •AST and ALT ≤3 × ULN (≤5 × ULN for participants with liver metastases)
• •TSH TSH within normal limits. If TSH is not within normal range despite no symptoms of thyroid dysfunction, normal free T4 level is required.
• •Age ≥ 18
• •A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• •* Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance
• •* For WOCBP: negative urine or serum pregnancy test is required
• •HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
• •Patients 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.
• •The participant provides written informed consent for the trial.
• •1. Has received prior therapy with an anti-PD-, anti-PD-L1 or anti-CTLA-4 agent.
• •2. Has received prior PARP inhibitor to include but not limited to olaparib, rucaparib, niraparib, talozaporib.
• •3. Has received prior lenvatinib or other VEGF TKI therapy to include but not limited to lucitinib, cederinib and cabozantonib in combination with anti-PD-1 or anti-PD-L1 therapy.
• •4. Has participated in a study of an investigational agent and received cancer directed study therapy within 4 weeks prior to start of study treatment.
• •5. Has received prior radiotherapy within 2 weeks of start of study treatment.
• •6. Has received a live vaccine within 30 days prior to the first dose of study drugs. 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.
• •7. 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 drugs.
• •* Steroids as CT scan contrast premedication is allowed
• •* The use of inhaled or topical corticosteroids is allowed
• •* The use of mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic hypotension or adrenocortical insufficiency is allowed.