285TiP - DANUBE: A Phase 3 randomised study of first-line durvalumab (MEDI4736) ± tremelimumab vs standard of care (SoC) chemotherapy (CT) in patients (pts)...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Drug Development
Urothelial Cancers
Cancer Immunology and Immunotherapy
Presenter Se Hoon Park
Authors S.H. Park1, D. Castellano2, D.P. Petrylak3, M.D. Galsky4, M.S. van der Heijden5, Y. Loriot6, O. Ogawa7, W. Su8, W. Huang9, W. Levin9, S. Ferro9, Y. Ben9, J. Bellmunt10, T. Powles11
  • 1Department Of Medicine, Samsung Medical Center, 06351 - Seoul/KR
  • 2Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid/ES
  • 3Department Of Medicine, Yale University, New Haven/US
  • 4Department Of Medicine, Icahn School of Medicine at Mount Sinai, New York/US
  • 5Department Of Medical Oncology, Netherlands Cancer Institute, Amsterdam/NL
  • 6Department Of Cancer Medicine, Institut Gustave Roussy, Villejuif/FR
  • 7Department Of Urology, Kyoto University, Kyoto/JP
  • 8Department Of Internal Medicine, National Cheng Kung University Hospital, Tainan/TW
  • 9Global Medicines Development, AstraZeneca, Gaithersburg/US
  • 10Bladder Cancer Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston/US
  • 11Experimental Cancer Medicine Centre, Barts Cancer Institute, Queen Mary University of London, London/GB

Abstract

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-lymphocyte-associated antigen-4 (CTLA-4) checkpoints may provide for non-redundant pathway blockade and potential additive or synergistic effects. Durvalumab is a selective, high-affinity, engineered human IgG1 mAb that blocks programmed cell death ligand-1 (PD-L1) 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 tremelimumab combination 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-naïve 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 75 mg i.v. q4w for 4 doses, followed by durvalumab 1500 mg i.v. q4w for up to 12 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 (RECIST v1.1). Secondary endpoints include overall survival; proportion of pts alive and progression free at 12 months, objective response rate, duration of response and disease control rate using investigator assessment; time to second progression; health-related quality of life; pharmacokinetics; immunogenicity; and safety and tolerability. Recruitment is ongoing.

Clinical trial indentification

NCT02516241