Background: Perioperative treatment of muscle-invasive bladder carcinoma (MIBC) remains cisplatin-based chemotherapy, but recent evidences suggest that immune checkpoint inhibitors could be incorporated in this setting. Durvalumab is a PD-L1 blocking antibody active in advanced urothelial carcinoma pretreated with platinum-containing chemotherapy and currently under evaluation in first-line, both as monotherapy and in combination with tremelimumab. Olaparib is a PARP inhibitor especially important in tumors with deficiencies in DNA repair mechanisms. Preliminary results from combination trials suggest that these drugs could have synergistic effect dependent on an immunogenic modulation related with STING pathway, and an increase of neoantigens. Unexpected toxicities have not been described. Methods:Design: Open label phase II single arm clinical trial. Primary Objective: To assess the impact of neoadjuvant treatment with durvalumab plus olaparib in the molecular profile of MIBC. Secondary Objectives: Efficacy (Radiological and pathological responses); Safety. Exploratory objective: To identify predictive and prognostic biomarkers. Key correlative studies: Independent central pathologist for histological review and assessment of immunohistochemistry for PD1, PD-L1 and PD-L2; Genomic characterization (WES) and Expression assessment (RNAseq) of the tumors pre and post treatment; Assessment of soluble biomarkers and their evolution during the treatment: flow cytometry for immune cells; immunoassays for cytokines; HLA genotyping. Treatment: Durvalumab 1500 mg iv Q4W & Olaparib 150 mg bid orally during 6 to a maximum of 8 weeks pre-cystectomy. Recruitment: 29 patients. Collaborating institutions: 10 (members of Spanish Oncology Genitourinary Group). Key Inclusion Criteria: Subjects with histological confirmation of T2-T4a MIBC aimed for cystectomy without neoadjuvant chemotherapy; Available samples for correlative studies; Adequate medullary, renal and hepatic function. Key Exclusion Criteria: Use of immunosuppressive medication; Documented autoimmune disorders. Clinical trial information: NCT03534492