A Multicentre Phase II Trial of Durvalumab Versus Physician's Choice Chemotherapy in Recurrent Ovarian Clear Cell Adenocarcinomas

Patient Inclusion Criteria Patients will be eligible for inclusion in this study if all of the following criteria apply: 1. Provision of signed, written and dated informed consent prior to any study specific procedure 2. Female aged 18 years (21 years in Singapore) or older 3. Have histologically documented diagnosis of ovarian clear cell carcinoma as evidenced by WT1 negativity. For tumors with a mixed histology, at least 70% of the tumor must consist of clear cell carcinoma. 4. Provision of an archived tumour tissue block (or at least 10 newly cut unstained slides) where such samples exist in a quantity sufficient to allow for analysis 5. Patients must have had a prior line of platinum-based chemotherap y in the course of their treatment paradigm 6. A maximum of 4 prior lines of systemic treatment regimens will be allowed and may include chemotherapy and biologics (prior immune checkpoint inhibitor treatment will not be permitted). 7. Meet RECIST criteria (version 1.1) within 28 days of start of treatment by having measurable disease defined as one or more lesions that can be accurately measured at baseline as ≥ 10mm in the longest diameter (except lymph nodes which must have a short axis of ≥ 15mm with CT or MRI and which is suitable for repeated measurements). Patients must have radiographic evidence of disease progression following most recent line of treatment. Areas of previous radiation may not serve as measurable disease unless there is evidence of progression post radiation. 8. At time of registration, if the patient has had previous treatment it must have been at least 4 weeks since major surgery or radiation therapy; four weeks from any other previous anti-cancer therapy including biologics. Patients must have recovered from their treatment-related events to ≤1 with the exception of alopecia and neuropathy (≤ 2 sufficient). 9. Have clinically acceptable laboratory screening results within certain limits specified below: * AST and ALT ≤ 2.5 times upper limit of normal (ULN), with the exception of: i. Patients with documented liver metastasis: AST and/or ALT ≤ 5 X ULN * Total bilirubin ≤ ULN; patients with known Gilbert disease who have serum bilirubin level ≤ 3 X ULN may be enrolled * Creatinine ≤ 1.5 x UL * Absolute neutrophil count ≥ 1500 cells/mm * Platelets ≥ 100,000/mm3 * Hemoglobin ≥ 9.0 g/dl 10. Have an ECOG performance status of ≤ 2. 11. Women of child-producing potential who are sexually active with a non sterilized male partner must agree to use at least one highly effective contraceptive method prior to study entry, during study participation, and for at least 90 days after the last administration of durvalumab 12. A serum pregnancy test within 72 hours prior to the initiation of therapy will be required for women of childbearing potential 13. Have the ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments. 14. Life expectancy greater than 12 weeks Patient Exclusion Criteria Patients will not be eligible for inclusion in this study if any of the following criteria apply: 1. Women who are pregnant or nursing 2. Prior exposure to an immune checkpoint inhibitor (anti-PD-1 or anti-PDL-1 antibody) 3. Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1 4. Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. 5. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) 6. Have active, acute, or chronic clinically significant infections or bleeding including but not limited to active bleeding diatheses, patients known to have evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), 7. History of primary immunodeficiency 8. History of allogeneic organ transplant 9. Known history of previous clinical diagnosis of tuberculosis 10. Have uncontrolled hypertension (systolic blood pressure greater than 150mmHg or diastolic blood pressure greater than 100mmHg); 11. Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months or unstable angina 12. Chronic atrial fibrillation or QTc interval corrected for heart rate of greater than 470 msec. calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction. • By Fridericia's formula: QTc = QT/(RR\^0.33) Where - RR interval = 60 / HR ; HR = Heart rate in beats per minute. 13. Have additional uncontrolled serious medical or psychiatric illness. 14. Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of investigational product 15. Require therapeutic doses of anti-coagulation with warfarin or warfarin derivatives. However, treatment with low molecular weight heparin (LMWH) is allowed. 16. Brain metastases or spinal cord compression unless asymptomatic, treated and stable off steroids and anti-convulsants for at least 1 month prior to entry into the study 17. History of leptomeningeal carcinomatosis 18. History of another primary malignancy unless treated with curative intent and with no known active disease ≥5 years except: * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease * Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ 19. Absence of a tumour sample (archival and/or recent). 20. Current or prior use of systemic immunosuppressive medications within 28 days before the first dose of durvalumab (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) * Patients on systemic corticosteroids at physiological doses, which do not exceed 10 mg/day of prednisone, or an equivalent corticosteroid are allowed * The use of inhaled corticosteroids and mineralocorticoids (e.g., fludrocortisone) is allowed. 21. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab 22. Patients who are pregnant, breast-feeding or of reproductive potential who are not employing an effective method of birth control 23. Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results