A Phase 2, Open-Label, Randomized Study of Pexa-Vec (JX-594) Administered by Intratumoral Injection in Patients with Unresectable Primary Hepatocellular Carcinoma

Methods Mol Biol. 2015;1317:343-57. doi: 10.1007/978-1-4939-2727-2_19.


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).

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Carcinoma, Hepatocellular / surgery
  • Carcinoma, Hepatocellular / therapy*
  • Follow-Up Studies
  • Humans
  • Image Processing, Computer-Assisted
  • Injections, Intralesional*
  • Kaplan-Meier Estimate
  • Liver Neoplasms / surgery
  • Liver Neoplasms / therapy*
  • Oncolytic Virotherapy / adverse effects
  • Oncolytic Virotherapy / methods*
  • Treatment Outcome
  • Vaccinia virus / physiology*