PHOCUS: A phase 3 randomized, open-label study comparing the oncolytic immunotherapy Pexa-Vec followed by sorafenib (SOR) vs SOR in patients with advanced hepatocellular carcinoma (HCC) without prior systemic therapy.

TPS4146Background: Pexa-Vec (pexastimogene devacirepvec; JX-594) is an oncolytic and immunotherapeutic vaccinia virus designed to selectively replicate in and destroy cancer cells. It causes direct oncolysis accompanied by tumor vascular disruption and anti-tumor immunity mediated by expression of the transgene GM-CSF. SOR, a multi-targeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced HCC. Both preliminary preclinical and clinical data suggest complementary anti-tumor effects of a sequential combination of Pexa-Vec followed by SOR possibly by targeting the tumor vasculature via different mechanisms (Heo et al., Mol Ther 2011). A randomized phase II dose-finding study with 3 Pexa-Vec intratumoral (IT) liver injections in first line advanced HCC patients showed an acceptable safety profile and a significant increase in overall survival (OS) in the highest dose group (109pfu) (Heo et al., Nat Med 2013). Methods: This global, randomized, open-label, phase II...