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

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Gene Therapy of Solid Cancers

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1317))

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 × 108 plaque forming units (pfu) versus 1 × 109 pfu).

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Authors and Affiliations

  1. SillaJen Inc, Seoul, South Korea

    Caroline J. Breitbach, Anne Moon, James Burke, Tae-Ho Hwang & David H. Kirn

  2. Pusan National University and Medical Research Institute, Pusan National University, 1-10 Ami-Dong, Seo-Gu, Busan, 602-739, South Korea

    Tae-Ho Hwang

Authors
  1. Caroline J. Breitbach
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  2. Anne Moon
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  3. James Burke
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  4. Tae-Ho Hwang
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  5. David H. Kirn
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Corresponding author

Correspondence to Caroline J. Breitbach .

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Editors and Affiliations

  1. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Wolfgang Walther

  2. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Berlin, Germany

    Ulrike Stein

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Breitbach, C.J., Moon, A., Burke, J., Hwang, TH., Kirn, D.H. (2015). A Phase 2, Open-Label, Randomized Study of Pexa-Vec (JX-594) Administered by Intratumoral Injection in Patients with Unresectable Primary Hepatocellular Carcinoma. In: Walther, W., Stein, U. (eds) Gene Therapy of Solid Cancers. Methods in Molecular Biology, vol 1317. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2727-2_19

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  • DOI: https://doi.org/10.1007/978-1-4939-2727-2_19

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2726-5

  • Online ISBN: 978-1-4939-2727-2

  • eBook Packages: Springer Protocols

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