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.
| Original language | English |
|---|---|
| Pages (from-to) | 329-336 |
| Number of pages | 8 |
| Journal | Nature Medicine |
| Volume | 19 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 2013 Mar 1 |
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All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)
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Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer. / Heo, Jeong; Reid, Tony; Ruo, Leyo; Breitbach, Caroline J.; Rose, Steven; Bloomston, Mark; Cho, Mong; Lim, Ho Yeong; Chung, Hyun Cheol; Kim, Chang Won; Burke, James; Lencioni, Riccardo; Hickman, Theresa; Moon, Anne; Lee, Yeon Sook; Kim, Mi Kyeong; Daneshmand, Manijeh; Dubois, Kara; Longpre, Lara; Ngo, Minhtran; Rooney, Cliona; Bell, John C.; Rhee, Byung Geon; Patt, Richard; Hwang, Tae Ho; Kirn, David H.
In: Nature Medicine, Vol. 19, No. 3, 01.03.2013, p. 329-336.Research output: Contribution to journal › Article
TY - JOUR
T1 - Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer
AU - Heo, Jeong
AU - Reid, Tony
AU - Ruo, Leyo
AU - Breitbach, Caroline J.
AU - Rose, Steven
AU - Bloomston, Mark
AU - Cho, Mong
AU - Lim, Ho Yeong
AU - Chung, Hyun Cheol
AU - Kim, Chang Won
AU - Burke, James
AU - Lencioni, Riccardo
AU - Hickman, Theresa
AU - Moon, Anne
AU - Lee, Yeon Sook
AU - Kim, Mi Kyeong
AU - Daneshmand, Manijeh
AU - Dubois, Kara
AU - Longpre, Lara
AU - Ngo, Minhtran
AU - Rooney, Cliona
AU - Bell, John C.
AU - Rhee, Byung Geon
AU - Patt, Richard
AU - Hwang, Tae Ho
AU - Kirn, David H.
PY - 2013/3/1
Y1 - 2013/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875225339&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875225339&partnerID=8YFLogxK
U2 - 10.1038/nm.3089
DO - 10.1038/nm.3089
M3 - Article
C2 - 23396206
AN - SCOPUS:84875225339
VL - 19
SP - 329
EP - 336
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 3
ER -