PMID- 38469652
OWN - NLM
STAT- Publisher
LR  - 20240312
IS  - 1464-410X (Electronic)
IS  - 1464-4096 (Linking)
DP  - 2024 Mar 12
TI  - The SUB-urothelial DUrvalumab InjEction-1 (SUBDUE-1) trial: first-in-human trial 
      in patients with bladder cancer.
LID - 10.1111/bju.16325 [doi]
AB  - OBJECTIVES: To assess the safety of sub-urothelial injection of durvalumab and 
      examine the impact on tissue and circulating immune cell populations. PATIENTS 
      AND METHODS: The patients were chemotherapy and immunotherapy naive (bacille 
      Calmette-Guerin allowed) with non-metastatic muscle-invasive bladder cancer or 
      non-muscle-invasive bladder cancer planned for radical cystectomy (RC). The study 
      was a Phase Ib 3 + 3 dose-escalation design with sub-urothelial injection of 
      durvalumab at three pre-determined doses (25, 75, 150 mg) diluted in 25 mL normal 
      saline, injected at 25 locations (25 x 1 mL injections), at least 2 weeks before 
      RC. RESULTS: A total of 11 patients were recruited (10 male, one female). No 
      significant changes were reported on American Urological Association Symptom 
      Score or O'Leary Interstitial Cystitis Scale. In all, 14 adverse events (AEs) 
      were reported (10 Grade 1, three Grade 2, one Grade 3), none considered 
      immune-related. No Grade 4 or 5 AEs were recorded. All the patients underwent RC. 
      Tissue immune populations changed following durvalumab injection (P = 0.012), 
      with a statistically significant increase in M2-macrophage (CD163) when comparing 
      the 25-150 mg dose (P = 0.021). Basal/mixed cancers showed a larger CD163 
      increase than luminal cancers (P = 0.033). CONCLUSION: Sub-urothelial injection 
      of durvalumab is feasible and safe without immune-related AEs and shows local 
      immunological effects.
CI  - (c) 2024 The Authors. BJU International published by John Wiley & Sons Ltd on 
      behalf of BJU International.
FAU - Hayne, Dickon
AU  - Hayne D
AUID- ORCID: 0000-0002-4094-401X
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - South Metropolitan Health Service, Murdoch, Western Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Ong, Katherine
AU  - Ong K
AD  - South Metropolitan Health Service, Murdoch, Western Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Swarbrick, Nicole
AU  - Swarbrick N
AD  - School of Pathology and Laboratory Medicine, University of Western Australia, 
      Crawley, Western Australia, Australia.
AD  - Department of Anatomical Pathology, PathWest Laboratory Medicine, Perth, Western 
      Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - McCombie, Steve P
AU  - McCombie SP
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - South Metropolitan Health Service, Murdoch, Western Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Moe, Andrew
AU  - Moe A
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Hawks, Cynthia
AU  - Hawks C
AUID- ORCID: 0000-0001-7848-9537
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - South Metropolitan Health Service, Murdoch, Western Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Viswambaram, Pravin
AU  - Viswambaram P
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Conduit, Ciara
AU  - Conduit C
AUID- ORCID: 0000-0001-5258-4130
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
AD  - Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
AD  - Sir Peter MacCallum Department of Medical Oncology, University of Melbourne, 
      Melbourne, Victoria, Australia.
AD  - Personalised Oncology, Walter and Eliza Hall Institute of Medical Research, 
      Parkville, Victoria, Australia.
FAU - Liow, Elizabeth
AU  - Liow E
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
AD  - Monash Health, Clayton, Victoria, Australia.
FAU - Spalding, Lisa
AU  - Spalding L
AD  - Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia.
AD  - University of Western Australia Centre for Medical Research, Nedlands, Western 
      Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Lim, Jayne
AU  - Lim J
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Ferguson, Thomas
AU  - Ferguson T
AD  - South Metropolitan Health Service, Murdoch, Western Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Meehan, Katie
AU  - Meehan K
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - Harry Perkins Institute of Medical Research, Perth, Western Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
FAU - Davis, Ian D
AU  - Davis ID
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
AD  - Monash University, Melbourne, Victoria, Australia.
AD  - Eastern Health, Melbourne, Victoria, Australia.
FAU - Redfern, Andrew D
AU  - Redfern AD
AD  - UWA Medical School, University of Western Australia, Crawley, Western Australia, 
      Australia.
AD  - South Metropolitan Health Service, Murdoch, Western Australia, Australia.
AD  - Australian and New Zealand Urogenital and Prostate (ANZUP) Cancer Trials Group, 
      Camperdown, New South Wales, Australia.
LA  - eng
GR  - Spinnaker Health Research Foundation/
GR  - Australian and New Zealand Urogenital and Prostate Cancer Trials Group/
PT  - Journal Article
DEP - 20240312
PL  - England
TA  - BJU Int
JT  - BJU international
JID - 100886721
SB  - IM
OTO - NOTNLM
OT  - SUBDUE-1
OT  - anti-PD-L1
OT  - bladder cancer
OT  - clinical trial
OT  - durvalumab
OT  - immunotherapy
OT  - sub-urothelial injection
OT  - urothelial carcinoma
EDAT- 2024/03/12 06:43
MHDA- 2024/03/12 06:43
CRDT- 2024/03/12 04:13
PHST- 2024/03/12 06:43 [medline]
PHST- 2024/03/12 06:43 [pubmed]
PHST- 2024/03/12 04:13 [entrez]
AID - 10.1111/bju.16325 [doi]
PST - aheadofprint
SO  - BJU Int. 2024 Mar 12. doi: 10.1111/bju.16325.