Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. Heo, J., Reid, T., Ruo, L., Breitbach, C. J., Rose, S., Bloomston, M., Cho, M., Lim, Yeong, H., Chung, Cheol, H., Kim, Won, C., Burke, J., Lencioni, R., Hickman, T., Moon, A., Lee, Sook, Y., Kim, Kyeong, M., Daneshmand, M., Dubois, K., Longpre, L., Ngo, M., Rooney, C., Bell, J. C., Rhee, B., Patt, R., Hwang, T., & Kirn, D. H. Nature Medicine, 19(3):329--336, March, 2013. ![Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 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.
@article{ heo_randomized_2013,
title = {Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia {JX}-594 in liver cancer},
volume = {19},
copyright = {© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
issn = {1078-8956},
url = {http://www.nature.com/nm/journal/v19/n3/full/nm.3089.html?WT.ec_id=NM-201303},
doi = {10.1038/nm.3089},
abstract = {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}.},
language = {en},
number = {3},
urldate = {2014-07-30},
journal = {Nature Medicine},
author = {Heo, Jeong and Reid, Tony and Ruo, Leyo and Breitbach, Caroline J. and Rose, Steven and Bloomston, Mark and Cho, Mong and Lim, Ho Yeong and Chung, Hyun Cheol and Kim, Chang Won and Burke, James and Lencioni, Riccardo and Hickman, Theresa and Moon, Anne and Lee, Yeon Sook and Kim, Mi Kyeong and Daneshmand, Manijeh and Dubois, Kara and Longpre, Lara and Ngo, Minhtran and Rooney, Cliona and Bell, John C. and Rhee, Byung-Geon and Patt, Richard and Hwang, Tae-Ho and Kirn, David H.},
month = {March},
year = {2013},
pages = {329--336},
file = {2013 Heo Nature Medicine - Randomized dose-finding clinical trial.pdf:C\:\\Users\̊je\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\5wru9u0w.default\\zotero\\storage\\ZFTW69JJ\\2013 Heo Nature Medicine - Randomized dose-finding clinical trial.pdf:application/pdf}
}
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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). 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All Rights Reserved.},\n issn = {1078-8956},\n url = {http://www.nature.com/nm/journal/v19/n3/full/nm.3089.html?WT.ec_id=NM-201303},\n doi = {10.1038/nm.3089},\n abstract = {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. 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