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Pexastimogene devacirepvec

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dose-ranging phase 2 study of Pexa-Vec in mainly sorafenib naĂŻve patients with advanced hepatocellular carcinoma demonstrated that the risk of death for patients who received Pexa-Vec at the high dose was markedly reduced (by nearly 60 percent; hazard ratio = 0.41) when compared to patients randomized to a low dose control (one-tenth of the high dose). The median overall survival for high and low dose groups was 14.1 months versus 6.7 months, respectively (p = 0.020 for superiority of the high dose). Pexa-Vec was well tolerated, with patients experiencing transient
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Pexa-Vec (JX-594) is the most advanced product candidate from SillaJen's proprietary SOLVE™ (Selective Oncolytic Vaccinia Engineering) platform. SOLVE is used to optimize virus targeting to specific cancer types, to select transgenes to include into the viral genome, and to optimize viral infection
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Heo, Jeong; Breitbach, Caroline; Cho, Mong; Hwang, Tae-Ho; Kim, Chang Won; Jeon, Ung Bae; Woo, Hyun Young; Yoon, Ki Tae; Lee, Jun Woo; Burke, James; Hickman, Theresa; Longpre, Lara; Patt, Richard H.; Kirn, David H. (2013-05-20). "Phase II trial of Pexa-Vec (pexastimogene devacirepvec; JX-594), an
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gene to stimulate a systemic anti-tumor immune response. Researchers believe that Pexa-Vec may be a systemic treatment of hepatocellular carcinoma by inducing tumor necrosis and shrinkage of both injected and non-injected tumors after direct intratumoral delivery. Final data from a randomized
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versus sorafenib is being conducted on patients with advanced hepatocellular carcinoma who have not previously received any systemic therapy. The study is being done to determine and compare overall survival for patients in the two treatment arms. The study is Sponsored by SillaJen, Inc.
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to stimulate immune responses. In nonclinical studies, the JX-970 backbone exerted a tumor debulking effect and at the same time demonstrated a selective preference for tumor tissues. The precursor of JX-970 is JX-963 which demonstrated efficacy in pre-clinical studies.
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Parker, Charles Thomas; Garrity, George M (2003-01-01). Parker, Charles Thomas; Garrity, George M (eds.). "Exemplar Abstract for Mycobacterium yongonense Kim et al. 2013 and Mycobacterium intracellulare yongonense (Kim et al. 2013) Castejon et al. 2018".
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Breitbach, Caroline J.; Burke, James; Jonker, Derek; Stephenson, Joe; Haas, Andrew R.; Chow, Laura Q. M.; Nieva, Jorge; Hwang, Tae-Ho; Moon, Anne (2011-08-31). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans".
1189:"A Trial to Evaluate the Safety and Efficacy of the Combination of the Oncolytic Immunotherapy Pexa-Vec With the PD-1 Receptor Blocking Antibody Nivolumab in the First-line Treatment of Advanced Hepatocellular Carcinoma" 231:
virus engineered to stimulate anti-tumor immunity and directly lyse tumor cells. Pexa-Vec has cancer selectivity through the deactivation of its thymidine kinase gene, and it has been engineered to express the
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Downs-Canner, Stephanie; Guo, Zong Sheng; Ravindranathan, Roshni; Breitbach, Caroline J; O'Malley, Mark E; Jones, Heather L; Moon, Anne; McCart, Judith Andrea; Shuai, Yongli (August 2016).
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Zeh, Herbert J.; Downs-Canner, Stephanie; McCart, J. Andrea; Guo, Zong Sheng; Rao, Uma N. M.; Ramalingam, Lekshmi; Thorne, Stephen H.; Jones, Heather L.; Kalinski, Pawel (January 2015).
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Zeh, Herbert J; Downs-Canner, Stephanie; McCart, J Andrea; Guo, Zong Sheng; Rao, Uma N M; Ramalingam, Lekshmi; Thorne, Stephen H; Jones, Heather L; Kalinski, Pawel (January 2015).
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via intratumoral & intravenous injections in a Phase 1, dose escalation clinical trial. This Phase 1 study showed delivery to and replication within tumors both IT and IV.
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Breitbach, Caroline J.; Arulanandam, Rozanne; De Silva, Naomi; Thorne, Steve H.; Patt, Richard; Daneshmand, Manijeh; Moon, Anne; Ilkow, Carolina; Burke, James (2013-02-15).
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Participants will be randomly assigned to one of two treatment arms, having an equal chance of receiving either Pexa-Vec followed by sorafenib, or sorafenib alone.
1169:"A Study of Metronomic CP and JX-594 in Patients With Advanced Breast Cancer and Advanced Soft-tissue Sarcoma (METROmaJX) - Full Text View - ClinicalTrials.gov" 581: 1149:"Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone - Full Text View - ClinicalTrials.gov" 799:
Kirn, David H.; Thorne, Steve H. (January 2009). "Targeted and armed oncolytic poxviruses: a novel multi-mechanistic therapeutic class for cancer".
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Transgene Presents Data on Improved Cytotoxic Activity of Oncolytic Viruses Expressing Intrabodies in Resistant Tumor Cell Lines. October 2016
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Blood flow to tumors can be blocked following intratumoral replication and spreadJX-900 (VVDD): VVDD Platform: Next-gen enhanced
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gene which limits viral replication to cells with high levels of thymidine kinase, typically seen in cancer cells with a mutated
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Phase 1 Study of Intratumoral Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus, in Pediatric Cancer Patients
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Participants will visit the study center approximately 12 times over 18 weeks and receive sorafenib as per standard of care.
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oncolytic and immunotherapeutic vaccinia virus, followed by sorafenib in patients with advanced hepatocellular carcinoma".
1315:"First-in-man study of western reserve strain oncolytic vaccinia virus: safety, systemic spread, and antitumor activity" 1010:"First-in-man Study of Western Reserve Strain Oncolytic Vaccinia Virus: Safety, Systemic Spread, and Antitumor Activity" 94: 1213:"Immunization Strategy With Intra-tumoral Injections of Pexa-Vec With Ipilimumab in Metastatic / Advanced Solid Tumors" 534: 1148: 39: 1096: 660:
Breitbach at al. (2011). "Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans".
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Following Pexa-Vec injection series completion, patients will receive sorafenib starting at week 6 of the study
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gene insertion under control of the p7.5 promoter. The virus kills the infected/cancer cells by
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pipeline are engineered through the Selective Oncolytic Vaccinia Engineering (SOLVE) platform.
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Jennerex Granted FDA Orphan Drug Designation for Pexa-Vec in Hepatocellular Carcinoma (HCC)
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and vaccinia growth factor. JX-929 has been administered as a monotherapy to patients with
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In clinical trials doses have been administered by intratumoral or intravenous injection.
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and utilizes the same tumor selectivity mechanisms as JX-929. In addition, it expresses
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All Pexa-Vec treatments (3) will be given by intratumoral injections into liver tumors.
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Participants will visit the study center approximately 14 times over 18 weeks.
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virus. JX-929's tumor selectivity has been optimized through deletion of
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and “arming” for expression of therapeutic transgene products (e.g.
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A phase 3 randomized, open-label, clinical trial of Pexa-Vec plus
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vaccine (Western Reserve strain) with enhanced oncolytic potency
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of the infected cancer cell and spread to adjacent cancer cells
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Tumor selective intratumoral replication of the virus leads to
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Clinical trials investigating Pexa-Vec (as of June 2018)
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JX-929 (vvDD expressing CD for 5-FU pro-drug) experience in
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and/or replication selectively through targeted mutations.
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JX-594 is a modified Copenhagen strain (or Wyeth strain)
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which may help initiate an anti-tumour immune response.
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JX-970 is also derived from a Western Reserve strain
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could have 3-prolonged attack on cancer: direct cell
38:) and was constructed in Dr. Edmund Lattime's lab at 515:granulocyte-macrophage colony-stimulating factor 234:granulocyte-macrophage colony-stimulating factor 200:granulocyte-macrophage colony-stimulating factor 157:JX-900 (VVDD): VVDD Platform: Next-gen enhanced 975: 973: 1267:Journal of Geophysical Research: Space Physics 1003: 1001: 481:JX-929 is derived from Western Reserve strain 1261:Thorne, R. M.; Horne, R. B. (December 2007). 8: 1237:"JX-900 Series > Pipeline > Sillajen" 981:"JX-900 Series > Pipeline > Sillajen" 566: 564: 562: 560: 932:CS1 maint: DOI inactive as of April 2024 ( 709: 707: 224:The experimental therapy, Pexa-Vec, is an 1403: 1346: 1286: 1041: 867: 595:"ras oncogenes in human cancer: a review" 172:Attenuation via “Double-Deletion” : 548: 546: 254: 220:Mechanism of Action of Pexa-Vec (Jx-594) 627:. National Cancer Institute. 2011-02-02 527: 947: 945: 943: 922: 911: 146:) enhance immune response to the tumor 1308: 1306: 1067: 1065: 1063: 1061: 953:"SOLVE > Technology > Sillajen" 715:"SOLVE > Technology > Sillajen" 434:Arm A: Pexa-Vec followed by sorafenib 7: 246:As of June 2018, these are the 202:) next generation of the VVDD series 23:is designed to target and destroy 14: 1135:10.1200/jco.2013.31.15_suppl.4122 165:JX-900 is a series of modified 1434:Experimental cancer treatments 1073:"General Information | PHOCUS" 97:and EUMA for the treatment of 72:gene. The virus also has the 56:engineered by addition of the 1: 869:10.1158/0008-5472.CAN-12-2687 593:Bos, JL (September 1, 1989). 127:activation, and antivascular 123:with replication and spread, 1123:Journal of Clinical Oncology 537:25 March 2012, Radio Canada 138:Induction of tumor-specific 95:Food and Drug Administration 469:Novel oncolytic viruses in 315:metronomic cyclophosphamide 40:Thomas Jefferson University 1455: 36:pexastimogene devacirepvec 535:Un virus contre le cancer 281:Hepatocellular carcinoma 275: 272: 269: 266: 263: 260: 60:gene and deletion of the 350:Colorectal Cancer 2L/3L 327:Renal Cell Carcinoma 2L 198:JX-970 (vvDD expressing 99:hepatocellular carcinoma 250:investigating Pexa-Vec. 159:oncolytic immunotherapy 151:oncolytic immunotherapy 140:cytotoxic T-lymphocytes 27:. It is also known as 921:Cite journal requires 908:(inactive 2024-04-17). 801:Nature Reviews. Cancer 178:vaccinia growth factor 625:"NCI Drug Dictionary" 1288:10.1029/2007ja012268 93:designation from US 1388:10.1038/mt.2016.101 1331:10.1038/mt.2014.194 1279:2007JGRA..11212214T 1026:10.1038/mt.2014.194 762:10.1038/nature10358 754:2011Natur.477...99B 682:10.1038/nature10358 674:2011Natur.477...99B 460:Pipeline candidates 257: 82:and also expresses 1217:ClinicalTrials.gov 1193:ClinicalTrials.gov 1129:(15_suppl): 4122. 1101:ClinicalTrials.gov 465:JX-Next Generation 255: 1376:Molecular Therapy 1319:Molecular Therapy 1014:Molecular Therapy 649:. 31 August 2011. 499:pancreatic cancer 423: 422: 180:gene inactivation 117:Oncolytic viruses 1446: 1418: 1417: 1407: 1382:(8): 1492–1501. 1367: 1361: 1360: 1350: 1310: 1301: 1300: 1290: 1258: 1252: 1251: 1249: 1248: 1241:www.sillajen.com 1233: 1227: 1226: 1224: 1223: 1209: 1203: 1202: 1200: 1199: 1185: 1179: 1178: 1176: 1175: 1165: 1159: 1158: 1156: 1155: 1145: 1139: 1138: 1117: 1111: 1110: 1108: 1107: 1093: 1087: 1086: 1084: 1083: 1069: 1056: 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856:Cancer Research 849: 848: 844: 813:10.1038/nrc2545 798: 797: 793: 738: 737: 733: 724: 722: 713: 712: 705: 659: 658: 654: 645: 644: 640: 630: 628: 623: 622: 618: 599:Cancer Research 592: 591: 587: 580: 576: 569: 558: 551: 544: 538: 533: 529: 524: 507: 479: 467: 462: 452: 436: 428: 248:clinical trials 222: 209: 207:Clinical trials 110: 21:oncolytic virus 12: 11: 5: 1452: 1450: 1442: 1441: 1436: 1426: 1425: 1420: 1419: 1362: 1325:(1): 202–214. 1302: 1253: 1228: 1204: 1180: 1160: 1140: 1112: 1088: 1057: 1020:(1): 202–214. 997: 969: 939: 923:|journal= 891: 842: 791: 731: 703: 652: 638: 616: 605:(17): 4682–9. 585: 574: 556: 542: 526: 525: 523: 520: 511:vaccinia virus 506: 503: 478: 475: 466: 463: 461: 458: 457: 456: 451: 448: 447: 446: 443: 440: 435: 432: 427: 424: 421: 420: 417: 414: 410:Combined with 408: 405: 402: 398: 397: 394: 389: 385:Combined with 383: 380: 377: 373: 372: 370: 367: 359:Combined with 357: 354: 351: 347: 346: 343: 340: 336:Combined with 334: 331: 328: 324: 323: 320: 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Index

oncolytic virus
cancer cells
Pexa-Vec
INN
Thomas Jefferson University
SillaJen
vaccinia
poxvirus
GM-CSF
thymidine kinase
RAS
p53
LacZ
lysis
GM-CSF
orphan drug
Food and Drug Administration
hepatocellular carcinoma
Oncolytic viruses
lysis
immune
lysis
cytotoxic T-lymphocytes
GM-CSF
oncolytic immunotherapy
oncolytic immunotherapy
vaccinia
thymidine kinase
vaccinia growth factor
solid tumors

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