Trial in Patients With Relapsed Ovarian Cancer

Inclusion criteria

• Platinum-sensitive disease: defined as disease progression ≥ 6 months following the last administered dose of platinum-based therapy. Patients must have received atleast one line of chemotherapy for platinum-sensitive disease. OR
• Platinum-resistant disease: defined as disease progression < 6 months following the last administered dose of platinum-based therapy.

OR

• Platinum-refractory disease: defined as lack of response or disease progression while receiving the most recent therapy.

Other key inclusion criteria:

• Histological confirmed ovarian, fallopian tube or peritoneal cancers.
• Histological types: high-grade serious, high-grade endometriod, undifferentiated, carcinosarcoma or mixed histology.
• Subjects must have at least 1 measurable lesion as defined by RECIST guidelines. This should not be the same lesion used for biopsy.
• Patients entering cohort A: Archival tumour tissue must be screened for CD73 and only CD73 positive patients (defined as >10% of tumor cells positive) will enter this trial.
• Patient agrees to undergo all analysis (blood, serum, tissue); radiological examinations according to protocol.
• Mandatory tumour biopsy before treatment (before day 0) and at day 56 of treatment.
• Patients must give informed consent.
• Patients must be at least 18 years of age.
• ECOG performance status 0-1
• Serum albumin >30g/l.
• Adequate organ function
• Life expectancy of at least 12 weeks.
• Patients must be fit to receive Investigational medical products (IMPs)

Exclusion criteria

• Subjects using immunosuppressive medications within 14 days.
• Immunodeficiency or organ transplant
• Live vaccines within 28 days prior to the first dose.
• Major surgery within 28 days prior to the first dose.
• Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial can-cers.
• Cancer therapies (chemotherapy, radiotherapy, surgery, immunotherapy, biologic or hormonal therapy) within 28 days prior to the first dose.
• Concurrent treatment with an investigational agent or participation in another clinical trial.
• Previous malignant disease: patients are not eligible for the study if actively being treated of inva-sive cancer other than ovarian cancer. Patients with previous malignant disease other than ovarian cancer who are relapse-free and treatment-free for more than three years may enter this study. Pa-tients with previous history of in-situ carcinoma, stage 1A cervical cancer or non-invasive basal cell and squamous cell skin carcinoma can enter this trial.
• Active infection including tuberculosis
• History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months.
• History of clinically significant hemorrhage in the past 3 months.
• Untreated CNS disease, leptomeningeal disease or cord compression. Subjects with treated dis-ease should have at least 4 weeks of neurologic and radiographic stability and be off steroids for 14 days.
• Significant cardiovascular disease's.
• Persistance of clinically relevant therapy related toxicity from previous anticancer therapy (any grade 3-4 toxicity or grade ≥2 neuropathy).
• Known hypersensitivity to the trial drugs, or to their excipients.
• Has had prior exposure to IMPs, or any other immunotherapy.
• Active or prior documented autoimmune or inflammatory disorders
• For cohorts B and C: Medical condition requiring current systemic anticoagulation, or a history of congenital hypercoagulable condition. Subjects taking aspirin at doses < 325 mg per day are eli-gible provided that prothrombin time is within the institutional range of normal. Use of local anti-coagulation for port maintenance is permitted