Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer

Exclusion Criteria

• •Previous failure of chemotherapy, or refusal to undergo chemotherapy or chemo-naive patients not suitable for chemotherapy.
• •WHO performance 0-1
• •Adequate organ system function as measured within 28 days prior to administration of study treatment, as defined below:
• •* Haemoglobin ≥ 10.0 g/dL, with no blood transfusion in the past 28 days.
• •* Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• •* Platelet count ≥ 100 x 109/L
• •* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (not applicable to Gilbert's syndrome)
• •* Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x ULN unless liver metastases are present in which case they must be ≤ 5x ULN
• •* Patients must have creatinine clearance estimated of ≥51 mL/min estimated using the Cockcroft-Gault equation or 24 hr urine clearance.
• •Life expectancy of at least 16 weeks.
• •Measurable disease as defined by RECIST 1.1 criteria
• •Able to swallow and retain oral medication.
• •A female is eligible to enter and participate in this study if there is:
• •Participation in another clinical study with an investigational product during the last month or previous enrolment in the present study.
• •Any previous treatment with PARP inhibitor, including olaparib and/or any previous treatment with a PD1 or PD-L1 inhibitor
• •History of another primary malignancy except for malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of investigational product and of low potential risk for recurrence or adequately treated non-melanoma skin cancer, lentigo maligna or carcinoma in situ.
• •History of leptomeningeal carcinomatosis, symptomatic uncontrolled brain metastases (≤2mg/ day corticosteroids started ≥4 weeks prior to treatment is accepted) and spinal cord compression (unless received definitive treatment and clinically stable for 28 days) .
• •Resting ECG with QTc \> 470 msec on 2 or more time points within a 24 hour period or family history of long QT syndrome
• •Concomitant use of known strong or moderate CYP3A inhibitors and inducers.