Phase I/II clinical trial of a genetically modified and oncolytic vaccinia virus GL-ONC1 in patients with unresactable, chemotherapy-resistant peritoneal carcinomatosis
| Autor: | Ursula Koppenhoefer, Christina Pfannenberg, Nisar P. Malek, Tanja Auth, Julia B. Sturm, Michael Bitzer, Tony Yu, Joerg Glatzle, Robert Moehle, M Zimmermann, Alfred Koenigsrainer, Falko Fend, Ulrich M. Lauer, Aladar A. Szalay |
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| Rok vydání: | 2013 |
| Předmět: | |
| Zdroj: | Journal of Clinical Oncology. 31:3098-3098 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2013.31.15_suppl.3098 |
| Popis: | 3098 Background: For therapy-resistant peritoneal carcinomatosis (PC) viruses exhibiting oncolytic properties open up new perspectives. Our phase I/II study in patients with refractory PC (NCT01443260) is designed to assess the safety, MTD, and anti-tumor activity of GL-ONC1, a recombinant vaccinia virus (VACV) genetically engineered to selectively replicate in and destroy cancer cells. Methods: GL-ONC1 was administered intraperitoneally up to 4 times every 28 days under a standard 3+3 dose escalation design. Safety was assessed using CTCAEv4.0. Anti-tumor activity was determined by “fluid biopsies” obtained via repetitive paracenteses and by serial PET-CT scans. Patient samples were collected for pharmacokinetics, pharmacodynamics and viral shedding analysis. Results: Up to now, 4 patients have received 10 doses of GL-ONC1 ranging from 107 to 108 infectious viral particles per application.Adverse events have generally been limited to grade 1/2, being mostly transient flu-like symptoms as well as increased abdominal pain resulting from treatment-induced peritonitis. No DLT was reported. No viral shedding was observed. In one gastric cancer patient, effective intraperitoneal replication of GL-ONC1 was demonstrated for more than 3 weeks. Using either anti-EpCAM or anti-VACV specific antibodies, around 5% of all ascitic cells were found to be EpCAM-positive 3 days after treatment in this patient, and only around 5-10% of these cancer cells were VACV positive at the same time point. In contrast, 4 days later (i.e. 7 days after virotherapeutic treatment), less than 2% of all ascitic cells were still EpCAM-positive, and more than 90% of these cancer cells were VACV positive. Of note, VACV-positive cancer cells morphologically showed significant degenerative changes. Conclusions: Preliminary data demonstrate that GL-ONC1 is well tolerated when infused intraperitoneally. Importantly, a single intraperitoneal delivery of GL-ONC1 was found to be sufficient to cause a dramatic decline in the number of malignant cells in the ascitic fluid, suggesting that GL-ONC1 effectively removes tumor cells in the ascites of patients with PC. Clinical trial information: NCT01443260. |
| Databáze: | OpenAIRE |
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