title: A Phase 2, Open-Label, Randomized Study of Pexa-Vec (JX-594) Administered by Intratumoral Injection in Patients with Unresectable Primary Hepatocellular Carcinoma.
abstract: Primary liver cancer (hepatocellular carcinoma; HCC) in patients not eligible for surgery or transplant is currently treated by locoregional therapeutic approaches, including trans-arterial chemoembolization and radiofrequency ablation. Sorafenib (Nexavar; Bayer/Onyx) is currently the only approved systemic therapy for patients having failed locoregional interventions. Oncolytic viruses are designed to selectively replicate within, and subsequently lyse, cancer cells by a unique mechanisms-of-action that is not cross-resistant with approved therapies (Kirn et al., Nat Med 7:781-787, 2001; Parato et al., Nat Rev Cancer 5:965-976, 2005; Chiocca, Nat Rev Cancer 2:938-950, 2002; Heise and Kern, J Clin Invest 105:847-851, 2000). Given that these therapeutics are self-amplifying in tumors, the impact of dose on patient outcome is unclear. Pexa-Vec (JX-594) is an oncolytic and immunotherapeutic vaccinia virus which was shown to be well tolerated by intratumoral injection and intravenous infusions in Phase 1 trials (Park et al., Lancet Oncol 9:533-542, 2008; Breitbach et al., Nature 477:99-102, 2011). We present the design of a randomized dose-finding trial of Pexa-Vec in patients with advanced HCC in which Pexa-Vec was delivered by intratumoral injection three times every 2 weeks at one of two dose levels (1 × 10(8) plaque forming units (pfu) versus 1 × 10(9) pfu).
authors.affiliation: SillaJen Inc, Seoul, South Korea, cbreitbach@sillajen.com.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Breitbach
authors.forename: Anne
authors.initials: A
authors.lastname: Moon
authors.forename: James
authors.initials: J
authors.lastname: Burke
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Hwang
authors.forename: David H
authors.initials: DH
authors.lastname: Kirn
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000601:surgery / Q000628:therapy*; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D015552:Injections, Intralesional; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000601:surgery / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods*; D016896:Treatment Outcome; D014616:Vaccinia virus / Q000502:physiology*