1087P - A mechanism of action study of intra-tumoral or intravenous dosing of enadenotucirev, an oncolytic adenovirus in patients with colon, lung, bladder...

Date 09 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Immunotherapy
Therapy
Presenter Rocio Garcia-Carbonero
Citation Annals of Oncology (2016) 27 (6): 359-378. 10.1093/annonc/mdw378
Authors R. Garcia-Carbonero1, V. Boni2, I. Duran3, M. Gil4, M. Espinosa3, R. Salazar4, A. Cubillo2, M. Jurado5, B. Champion6, S. Alvis6, K. Fisher6, J. Beadle6, G. Pover6, H. McElwaine-Johnn6, C. Ellis6, C. Blanc6, E. Calvo2
  • 1Servicio De Oncología Médica, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 2Oncology, START-Madrid, Madrid/ES
  • 3Oncology, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 4Medical Oncology, Catalan Institute of Oncology, 08907 - L´Hospitalet/ES
  • 5Clinical Research, Pivotal, Madrid/ES
  • 6Research & Development, PsiOxus Therapeutics Limited, OX14 4SD - Abingdon/GB

Abstract

Background

Demonstrating intravenous (IV) delivery in patients is key for the development of enadenotucirev (EnAd), a tumor selective chimeric Ad11/Ad3 group B adenovirus. Initial results from colon cancer (CC) patients receiving intra-tumoral (IT) or IV administration have been reported [ESMO 2015 Abstract 1086P]. Here we report the full study results, including an expansion to include lung (NSCLC), bladder and renal (RCC) cancer patients. The primary study objective was to describe the pattern of EnAd delivery within tumors.

Methods

Patients with histologically confirmed cancer scheduled for surgical removal of primary tumor received either 1x1012 viral particles (VP) IV over 5 min on D 1, 3 and 5; or 1011 VP/mL IT with a variable volume injected based on the tumor surface area on D 1. Immunohistochemistry (IHC) staining of formalin fixed (FFPE) sections for EnAd hexon protein (only produced late during replication), was used to visualise virus activity. A quantitative polymerase chain reaction (qPCR) specific to EnAd was used to detect virus genome. Further IHC studies were conducted with a panel of immune markers and gene expression was analysed using RNA extracted from FFPE sections (Nanostring).

Results

The study recruited 10 CC (5 IT / 5 IV), 2 bladder, 2 NSCLC and 3 RCC (all IV) patients. Surgery was between D 8 and 51. IV and IT EnAd was well tolerated with common adverse events consistent with ‘flu like illness as previously described. Both IHC staining and qPCR confirm that IV dosing can deliver EnAd selectively to all 4 tumor types and is as reliable as IT in CC. Evidence of enhanced immune responses in tumors included high levels of CD8+ cells within tumor nests and peritumoral stroma. CD4+ cells were largely restricted to stroma. Nanostring highlighted potential treatment-responsive genes for further evaluation.

Conclusions

Delivery of EnAd to tumor cells following IV dosing has been confirmed by IHC and qPCR studies of surgically resected tumor samples from patients with CC, NSCLC, RCC and bladder cancer. Delivery appears to be associated with inflammatory changes within the first weeks after administration.

Clinical trial identification

EudraCT 2012-001067-79

Legal entity responsible for the study

PsiOxus Therapeutics Limited

Funding

PsiOxus Therapeutics Limited

Disclosure

B. Champion, S. Alvis, K. Fisher, H. McElwaine-Johnn, C. Ellis: Stock options in PsiOxus. J. Beadle: Chief Executive Officer, serves as a board member and holds stock options in PsiOxus. All other authors have declared no conflicts of interest.