285Tip DANUBE: A Phase 3 Randomised Study of First-Line Durvalumab (MEDI4736) 6 Tremelimumab Vs Standard of Care (soc) Chemotherapy (CT) in Patients (pts) with Stage IV Urothelial Carcinoma (UC)

Background Standard first-line treatment options for metastatic UC (cisplatin-based CT or carboplatin-based CT for cisplatin-ineligible pts) are associated with suboptimal long-term outcomes. New first-line therapies are urgently needed. Immune checkpoint blockade is a promising anticancer strategy that has shown activity in CT-resistant UC. Targeting both programmed cell death-1 (PD-1) and cytotoxic T-lymphocyteassociated antigen-4 (CTLA-4) checkpoints may provide for non-redundant pathway blockade and potential additive or synergistic effects. Durvalumab is a selective, highaffinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PDL1) binding to PD-1 and CD80. Tremelimumab is an anti-CTLA-4 lgG2 kappa mAb. In a Phase 1/2 study (NCT01693562), single-agent durvalumab showed preliminary evidence of activity across multiple tumour types, including UC. Manageable tolerability was reported in a Phase 1b study of durvalumab and tremelimumabcombination regimens in advanced NSCLC, with clinical activity observed in patients with high and low/no tumour PD-L1 expression (NCT02000947). Trial design: DANUBE is a randomised, open-label, multicentre, global Phase 3 study (NCT02516241) assessing durvalumab ± tremelimumab vs SoC CT in treatment-naive pts with unresectable and/or metastatic UC. Pts will be randomised 1:1:1 to durvalumab 1500 mg i.v. q4w for up to 12 months; durvalumab 1500 mg i.v. q4w + tremelimumab 75mgi.v.q4wfor4doses,followedbydurvalumab1500mgi.v. q4wforupto12 months; or SoC (cisplatin + gemcitabine or carboplatin + gemcitabine) for up to 6 cycles (stratification factors: cisplatin eligibility, PD-L1 expression and visceral metastasis). The primary endpoint is investigator-assessed progression-free survival (RECISTv1.1).Secondaryendpointsincludeoverallsurvival;proportionofptsalive and progression free at 12 months, objective response rate, duration of response and disease control rate using investigator assessment; time to second progression; health- relatedqualityoflife;pharmacokinetics;immunogenicity;andsafetyandtolerability. Recruitment is ongoing. Clinical trial indentification NCT02516241 Legal entity responsible for the study AstraZeneca PLC Funding AstraZeneca Disclosure D.P. Petrylak: Consulting/Advisory/Travel/Accommodation/Expenses/ Honoraria: Bayer, Bellicum Pharmaceuticals, Dendreon, Sanofi, J&J, Exelixis, Ferring, Medivation, Pfizer, OncoGenex, Progenics, Millennium, Celgene. M.D. Galsky: Consulting/Advisory: AZ, Genentech Research funding: BMS, Merck. M.S. van der Heijden: Consulting/Advisory: AZ/Medimmune, Roche/Genentech, Astellas, Bayer (paid to institute) Research funding: Astellas Pharma (Institute) Travel/ Accommodation/Expenses: MSD, Astellas. Y. Loriot: Honoraria: Astra Zeneca, Astellas, Roche, Janssen, Sanofi Consulting or advisory: Astra Zeneca, Astellas, Roche, Research funding: Astellas, Sanofi Travel, accommodations, expenses: Astellas, Roche, Sanofi. W. Huang: Employment: AstraZeneca Stock: AstraZeneca. W. Levin: Employment: AstraZeneca. S. Ferro: Employment: AstraZeneca Stock/Ownership: Amgen. Y. Ben: Employment: AstraZeneca Stock/Ownership: AstraZeneca. J. Bellmunt: Employment: Dana Farber Cancer Institute Honoraria: paid consultancy/adboard for AstraZeneca, Pfizer, Novartis, Genentech and Merck Research funding: Takeda, Novartis and Sanofi Travel/Accommodation: Expenses: Pfizer and Pierre Fabre. T. Powles: Honoraria: Roche/Genentech, Novartis, BMS Consulting/Advisory: Roche/Genentech; Novartis; BMS; Merck Research Funding: AZ; Roche/Genentech, GSK. All other authors have declared no conflicts ofinterest.