Z Gastroenterol 2012; 50 - K151
DOI: 10.1055/s-0032-1324086

Phase I Clinical Trial of a Genetically Modified and Oncolytic Vaccinia Virus GL-ONC1 in patients with peritoneal carcinomatosis

UM Lauer 1, M Zimmermann 1, U Koppenhöfer 1, M Bitzer 1, NP Malek 1, A Königsrainer 2, R Möhle 3, F Fend 4, C Pfannenberg 5, JS de Bono 6, K Harrington 6, YA Yu 7, A Röder 8, AA Szalay 7
  • 1Medical University Hospital, Tübingen, Department of Gastroenterology & Hepatology, Tübingen, Germany
  • 2University Hospital, Tübingen, Department of General, Visceral and Transplant Surgery, Tübingen, Germany
  • 3Medical University Hospital, Tübingen, Department of Internal Medicine II, Tübingen, Germany
  • 4University Hospital, Tübingen, Institute for Pathology, Tübingen, Germany
  • 5University Hospital, Tübingen, Department for Diagnostic and Interventional Radiology, Tübingen, Germany
  • 6Royal Marsden Hospital, The Institute of Cancer Research, London, United Kingdom
  • 7Genelux Corporation, San Diego, United States
  • 8Genelux GmbH, Bernried, Germany

Introduction: Patients exhibiting advanced stages of peritoneal carcinomatosis that are refractory to standard therapy (i.e., cytoreductive surgery (CRS) plus HIPEC), urgently require new therapeutic approaches like virotherapeutic regimens.

Methods: GL-ONC1 is a genetically engineered oncolytic vaccinia virus attenuated by insertion of the RUC-GFP (Renilla luciferase and Aequorea green fluorescent protein fusion gene), beta-galactosidase (lacZ) and beta-glucuronidase (gusA) reporter genes into the F14.5L, J2R (thymidine kinase, TK) and A56R (hemagglutinin, HA) loci, respectively.

Results: A first clinical trial running at the Royal Marsden Hospital has provided first evidence that GL-ONC1 administered intravenously is well tolerated together with preliminary evidence of anti-tumour activity in patients with advanced solid organ cancers. In our Tübingen trial, GL-ONC1 is administered intraperitoneally in patients exhibiting peritoneal carcinosis originating from CRC, HCC, CC, gastric and ovarian cancer, and others. Further data on both safety and (peritoneal and systemic) efficacy of GL-ONC1 obtained by our dose escalating study will be presented.

Perspectives: To our best knowledge, the Tübingen virotherapy trial is the first one in Germany employing a recombinant oncolytic viral vector thereby opening up new perspectives in patients exhibiting advanced gastrointestinal and non-gastrointestinal cancers. As a „strategic” advantage GL-ONC1 is brought into direct contact with peritoneal carcinosis by intraperitoneal application which should ensure an effective „colonisation” of solid tumor nodules and subsequent systemic oncolytic as well as immunovirotherapeutic effects.

Acknowledgement: Sponsor of the trial: Genelux GmbH & Genelux Corporation.

References: www.clinicaltrials.gov; Identifiers: NCT01443260 & NCT00794131.