Evaluating antivascular effects and antitumoral activity in patients with hepatocellular carcinoma treated with JX-594, a targeted multimechanistic oncolytic poxvirus, prior to sorafenib therapy.

Abstract

e14564 Background: JX-594 is a first-in-class targeted oncolytic poxvirus designed to selectively replicate in and destroy cancer cells with epidermal growth factor receptor (EGFR)/ ras pathway activation. Direct oncolysis plus granulocyte macrophage, colony stimulating factor (GM-CSF) expression stimulates acute tumor vascular shutdown and antitumoral immunity. JX-594 has been shown to be well tolerated by intravenous (IV) infusion and intratumoral (IT) injection and JX-594 is being developed as a novel therapy for patients with refractory hepatocellular carcinoma (HCC). Sorafenib is an antiangiogenic agent approved for patients with advanced HCC. Complementary antitumor effects are predicted with these two agents due to acute vascular disrupting effects of JX-594 and chronic antiangiogenic effects of sorafenib. Methods: Patients with confirmed treatment-refractory HCC were treated with JX-594 followed by standard sorafenib therapy. A subset of patients had previously received and failed sorafenib therap...