Z Gastroenterol 2015; 53 - KG204
DOI: 10.1055/s-0035-1559230

Final results of the first phase I study of intraperitoneal administration of GL-ONC1, a marker gene modified vaccinia virus, in patients with peritoneal carcinomatosis

U Lauer 1, M Zimmermann 1, J Beil 1, S Berchtold 1, U Koppenhöfer 1, J Glatzle 2, A Königsrainer 2, R Möhle 3, D Nann 4, F Fend 4, C Pfannenberg 5, M Bitzer 1, N Malek 1
  • 1Universitätsklinikum Tübingen, Innere Medizin I, Gastroentologie, Hepatologie, Infektionskrankheiten, Tübingen, Deutschland
  • 2Universitätsklinikum Tübingen, Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie, Tübingen, Deutschland
  • 3Universitätsklinikum Tübingen, Innere Medizin II, Tübingen, Deutschland
  • 4Universitätsklinikum Tübingen, Institut für Pathologie, Tübingen, Deutschland
  • 5Universitätsklinikum Tübingen, Radiologische Universitätsklinik, Diagnostische und Interventionelle Radiologie, Tübingen, Deutschland

Introduction: We here report on our final results of a phase I study of intraperitoneal (i.p.) administration of the virotherapeutic drug GL-ONC1 in patients exhibiting advanced stage peritoneal carcinomatosis (PC). GL-ONC1 is a recombinant Vaccinia virus genetically engineered to selectively replicate in and destroy cancer cells.

Methods: GL-ONC1 was administered i.p. every 4 weeks for up to 4 cycles at 3 different dose levels (10E7 – 10E9 pfu) following a standard 3 + 3 dose escalation design. GL-ONC1 was infused via an indwelling catheter which also enabled repetitive liquid (peritoneal fluid) biopsies and therefore real-time monitoring of GL-ONC1-mediated anti-tumoral activities. Primary study objective was safety of GL-ONC1, regarding this intraperitoneal application route.

Results: Nine patients with advanced stage PC received 24 doses of GL-ONC1 in total. Adverse events were found to be limited to grades 1 – 3, including transient flu-like symptoms and increased abdominal pain, resulting from treatment-induced peritonitis. No DLT was reported. Furthermore, no signs of viral shedding were observed. Importantly, in 8 out of 9 study patients effective intraperitoneal infections and in-patient replication of GL-ONC1 as well as subsequent oncolysis was demonstrated. Interestingly, the pre-vaccination status did not exert any negative impact on primary infections. All study patients developed neutralizing antibodies against GL-ONC1, at earliest on day 8 of cycle 1.

Conclusions: Our data demonstrate that GL-ONC1 is well tolerated when infused intraperitoneally and does not lead to any viral shedding. Importantly, both lower and higher doses of intraperitoneally administered GL-ONC1 were found to be capable to infect, replicate in and significantly lyse tumor cells in all tumor entities being addressed. Tracking of tumor cell colonization, in-patient virus replication, and oncolysis yielded important information on safety as well as efficiency of this novel virotherapeutic approaches. Based on these findings, future studies will focus on combinations with checkpoint blocking antibodies, further enhancing virotherapy induced anti-tumoral immune responses (funded by Genelux GmbH, Bernried, Germany; ClinicalTrials.gov number: NCT01443260).