Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer

Jeong Heo, Tony Reid, Leyo Ruo, Caroline J. Breitbach, Steven Rose, Mark Bloomston, Mong Cho, Ho Yeong Lim, Hyun Cheol Chung, Chang Won Kim, James Burke, Riccardo Lencioni, Theresa Hickman, Anne Moon, Yeon Sook Lee, Mi Kyeong Kim, Manijeh Daneshmand, Kara Dubois, Lara Longpre, Minhtran NgoCliona Rooney, John C. Bell, Byung Geon Rhee, Richard Patt, Tae Ho Hwang, David H. Kirn

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532 Citations (Scopus)


Oncolytic viruses and active immunotherapeutics have complementary mechanisms of action (MOA) that are both self amplifying in tumors, yet the impact of dose on subject outcome is unclear. JX-594 (Pexa-Vec) is an oncolytic and immunotherapeutic vaccinia virus. To determine the optimal JX-594 dose in subjects with advanced hepatocellular carcinoma (HCC), we conducted a randomized phase 2 dose-finding trial (n = 30). Radiologists infused low- or high-dose JX-594 into liver tumors (days 1, 15 and 29); infusions resulted in acute detectable intravascular JX-594 genomes. Objective intrahepatic Modified Response Evaluation Criteria in Solid Tumors (mRECIST) (15%) and Choi (62%) response rates and intrahepatic disease control (50%) were equivalent in injected and distant noninjected tumors at both doses. JX-594 replication and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression preceded the induction of anticancer immunity. In contrast to tumor response rate and immune endpoints, subject survival duration was significantly related to dose (median survival of 14.1 months compared to 6.7 months on the high and low dose, respectively; hazard ratio 0.39; P = 0.020). JX-594 demonstrated oncolytic and immunotherapy MOA, tumor responses and dose-related survival in individuals with HCC.

Original languageEnglish
Pages (from-to)329-336
Number of pages8
JournalNature Medicine
Issue number3
Publication statusPublished - 2013 Mar

Bibliographical note

Funding Information:
J.-M. Limacher, M. Homerin, B.M. Bastien and M. Lusky (all from Transgene SA) gave insightful comments on the manuscript. T.-H.H. and M.K.K. were supported by a grant of the Korea Healthcare technology Research and Development Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea (A091047). C.R. was supported by a pilot grant from the Dan Duncan Cancer Center. M.N. was supported by the Robert and Janice McNair Foundation and Baylor Research Advocates for Student Scientists Fund. J.C.B. is supported by the Ontario Institute for Cancer Research and the Terry Fox Foundation. Funding was provided by Jennerex, Transgene SA (Illkirch, France) and the Green Cross Corporation; grants to T.-H.H. from Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea; to J.C.B. from the Terry Fox Foundation and the Canadian Institute for Health Research (CIHR); and a pilot grant to C.R. from the Dan Duncan Cancer Center. This trial was registered with ClinicalTrials.gov, number NCT00554372.

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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