A phase II trial of JX-594, a targeted multimechanistic oncolytic vaccinia virus, followed by sorafenib in patients with advanced hepatocellular carcinoma (HCC).

e14566 Background: JX-594 is a targeted oncolytic vaccinia virus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus GM-CSF expression is accompanied by tumor vascular disruption and anti-tumoral immunity (Reviewed in Nat Rev Cancer 2009). JX-594 was well-tolerated intravenously (IV) (Nature 2011) and intratumorally (IT) (Lancet Oncol 2008). Complementary anti-tumor effects are predicted with JX-594 followed by sorafenib due to acute vascular disruption effects with JX-594 and anti-angiogenic effects with sorafenib. Methods: Treatment-refractory HCC patients received JX-594 for three weeks (Day 1 IV, Day 8 IT and Day 22 IT) followed by sorafenib. An IT boost dose of JX-594 at Week 12 was optional. The primary objective of the study was to determine the safety of JX-594 followed by sorafenib in patients with advanced HCC. Secondary objectives include disease control rate (DCR) based on mRECIST and/or Choi ...