Durvalumab and Olaparib in Metastatic or Recurrent Endometrial Cancer

Inclusion criteria:

* Written informed consent
* Age \> 18 years old
* Histologically confirmed diagnosis of endometrial cancer or carcinosarcoma of the endometrium.
* Metastatic disease or locally advanced tumor not amenable to local therapy.
* Documented progressive disease before enrolment.
* Measurable lesions outside irradiated field or progressive measurable lesions in irradiated area
* Not eligible for hormonal therapy (because of negative hormone receptor/poor differentiation, or after failure of hormonal therapy).
* 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:

Exclusion criteria:

* 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.
* Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.
* Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab (except intranasal and inhaled corticosteroids or systemic prednisone ≤ 10 mg/day)
* Major surgery ≤2 weeks of starting study treatment
* History of active primary immunodeficiency
* Active or prior documented autoimmune or inflammatory disorders, with exception of: vitiligo or alopecia, hypothyroidism stable on hormone replacement, any chronic skin condition that does not require systemic therapy, celiac disease controlled by diet alone
* Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
* Active infection including tuberculosis, hepatitis B/C and HIV
* Patients with an expected or known hypersensitivity to olaparib or durvalumab or any of the excipients of the products.
* Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
* Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
* Pregnancy or breastfeeding