Phase I study of oncolytic vaccinia virus GL-ONC1 in patients with peritoneal carcinomatosis

Objective: Peritoneal carcinomatosis (PC) is common in advanced tumor stages or disease recurrence arising from gastrointestinal cancers, gynecologic malignancies, or primary peritoneal carcinoma. Since current therapies are mostly ineffective, new thera­peutic approaches are needed. Here, we report on a phase I study designed to assess safety, MTD, and anti-tumor activity of intra­peri­toneal (i.p.) administration of oncolytic vaccinia virus GL-ONC1 in advanced stage PC patients. Design: GL-ONC1 was administered i.p. every four weeks for up to four cycles at three different dose levels (10⁷-10⁹ pfu) following a standard 3 + 3 dose escalation design. GL-ONC1 was infused via an indwelling catheter which enabled repetitive analyses of peritoneal fluid biopsies. The primary study objective was safety of GL-ONC1 according to Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv4.0). Results: Patients with advanced stage PC (n=7) or advanced peritoneal mesothelioma (n=2) received 24 doses of GL-ONC1. Adverse events were limited to grades 1-3, including transient flu-like symptoms and increased abdominal pain, resulting from treatment-induced peritonitis. No DLT was reported and the MTD was not reached. Furthermore, no signs of viral shedding were observed. Importantly, in eight out of nine study patients effective i.p. infections, in-patient replication of GL-ONC1, as well as sub­sequent oncolysis were demonstrated in cycle 1. All patients developed neutralizing activities against GL-ONC1. Conclusions: GL-ONC1 was well tolerated when administered into the peritoneal cavity of patients with advanced stage PC. Efficient tumor cell infection, in-patient virus replication as well as onco­lysis were limited to treatment cycle 1. (ClinicalTrials.gov number, NCT01443260)

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