RadMD Principal, Rick Patt, MD was recently published in Nature Medicine magazine.
The article entitled “Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer” was published in March 2013.
Abstract:
Jeong Heo1,17, Tony Reid2,17, Leyo Ruo3, Caroline J Breitbach4, Steven Rose2, Mark Bloomston5,
Mong Cho1, Ho Yeong Lim6, Hyun Cheol Chung7, Chang Won Kim1, James Burke4, Riccardo Lencioni8,
Theresa Hickman4, Anne Moon4, Yeon Sook Lee9, Mi Kyeong Kim9, Manijeh Daneshmand10, Kara Dubois4,
Lara Longpre4, Minhtran Ngo11,12, Cliona Rooney11-13, John C Bell4,10, Byung-Geon Rhee14, Richard Patt15,
Tae-Ho Hwang9,16,18 & David H Kirn4,18
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.
1. Department of Internal Medicine, Pusan National University and Medical Research Institute, Pusan National University Hospital, Seo-Gu, Busan, South Korea.
2. Moores Cancer Center, University of California San Diego (UCSD), La Jolla, California, USA.
3. Department of Surgery, McMaster University Medical Centre, Hamilton, Ontario, Canada.
4. Jennerex Inc., San Francisco, California, USA.
5. Department of Surgery, The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, USA.
6. Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Ilwon-Dong, Gang Nam-Gu, Seoul, South Korea.
7. Yonsei Cancer Center, Yonsei University College of Medicine, Seodaemun-gu, Yongdong Severance Hospital, Seoul, South Korea.
8. Division of Diagnostic Imaging and Intervention, Pisa University School of Medicine, Lungarno Pacinotti, Pisa, Italy.
9. SillaJen Inc., GeumJung-Gu, Busan, South Korea.
10. Centre for Innovative Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
11. Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA.
12. Baylor College of Medicine, Houston, Texas, USA.
13. Texas Children’s Hospital, Houston, Texas, USA.
14. Green Cross Corporation, Giheung-gu, Yongin, South Korea.
15. RadMD, Doylestown, Pennsylvania, USA.
16. Department of Pharmacology, Pusan National University, Busan, South Korea.
17. These authors contributed equally to this work.
18. These authors jointly directed this work. Correspondence should be addressed to D.H.K. (dkirn@jennerex.com) or T.-H.H. (thhwang@pusan.ac.kr).