1068P - A phase 1 mechanism of action study of intra-tumoural (IT) or intravenous (IV) administration of enadenotucirev, an oncolytic Ad11/Ad3 chimeric gro...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Colon Cancer
Cancer Immunology and Immunotherapy
Translational Research
Presenter Valentina Boni
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors V. Boni1, F. De La Portilla2, A. Cubillo3, M. Gil-Martin4, E. Calvo5, R. Salazar4, C. Santos4, A. Sanchez-Gastaldo6, S. Prados1, X. Sanjuan7, J.M. Bozada8, H. Duran9, M. Jurado10, C. Ellis11, S. Alvis11, J. Beadle11, K. Fisher11, C. Blanc11, R. Garcia-Carbonero12
  • 1Department Of Gastroenterology, Centro Integral Oncologico Clara Campal, Hospital Madrid Norte Sanchinarro, 28050 - Madrid/ES
  • 2Surgery Department, Hospital Universitario Virgen del Rocio, 41013 - Sevilla/ES
  • 3Oncology, Hospital Sanchinarro/START, 28050 - Madrid/ES
  • 4L' Hospitalet-barcelona, Early Clinical Research Unit, Institut Catala D'Oncologia, ES-08907 - Barcelona/ES
  • 5Start Madrid, Early Clinical Drug Development Unit, Hospital Madrid Norte San Chinarro Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 6Ugc Oncologia Integral, Hospital Universitario Virgen Del Rocio, Sevilla/ES
  • 7Hospital Universitari Bellvitge-idibell, L'hospitalet-barcelona, Pathology Department, Barcelona/ES
  • 8Gastroenterology Department, Hospital Universitario Virgen Del Rocio, Sevilla/ES
  • 9Department Of Surgery, Centro Integral Oncologico Clara Campal, Hospital Madrid Norte Sanchinarro, Madrid/ES
  • 10Clinical Research, Pivotal, Barcelona/ES
  • 11Project Management, PsiOxus Therapeutics Limited, OX14 4SD - Abingdon/GB
  • 12Oncology Department, Hospital Universitario Virgen del Rocio, Sevilla/ES

Abstract

Aim

Enadenotucirev (EnAd) is a tumour selective chimeric Ad11/Ad3 group B adenovirus that has demonstrated preclinical activity in a model of colorectal cancer. Colon cancer (CC) patients (pts) scheduled for resection of primary or metastatic tumour present a window of opportunity to evaluate viral delivery to tumour, lymph nodes and normal margins in resected tissues following presurgical IT or IV EnAd administration.

Methods

CC pts scheduled for surgery received either 1012 EnAd viral particles (vp) IV on days (D) 1, 3 and 5 over 5 min (5 pts) or 1011 vp/mL IT with a variable volume injected based on the tumour surface area (4pts). Surgery was performed 7–15 days post first EnAd dose. The primary objectives were to determine whether EnAd is delivered to tumour tissues and to assess EnAd spread within the tissue following IV and IT dosing. IHC staining of EnAd hexon protein was used to visualise virus infection and replication. Other objectives included assessment of tumour cell death, immune modulation associated with virus activity by co-staining for immune markers, endothelial cells and myofibroblasts, as well as expression of EnAd uptake receptors (CD46 & DSG). Safety, and antibody responses were also assessed.

Results

9 pts have been treated, 4 IT and 5 IV. Adverse events (AEs) were generally mild. EnAd related AEs included mostly symptoms of flu like illness and asthenia and were only seen in the IV cohort. Grade 1 asthenia was the only EnAd related AE ongoing at time of surgery (2 pts). EnAd was readily detectable by IHC staining of hexon protein in a high percentage of tumour cells from both cohorts, indicating that EnAd is delivered to tumour cells at least as efficiently by IV dosing as by IT dosing. EnAd hexon protein detection in the nuclei of tumour cells also demonstrates viral replication in situ. Co-staining for markers and assessment of anti-EnAd antibody responses are ongoing.

Conclusions

Effective and well tolerated delivery of EnAd to tumour cells following IV dosing has been confirmed by IHC on surgically resected colon cancer tumour samples.

Disclosure

C. Ellis, S. Alvis, K. Fishe and C. Blanc: Employee and shareholder; J. Beadle: Employee, Shareholder, Director and Office Bearer . All other authors have declared no conflicts of interest.