You have accessJournal of UrologyProstate Cancer: Advanced (including Drug Therapy) I1 Apr 2016PD28-12 A PHASE 1 STUDY OF A THIRD-GENERATION ONCOLYTIC HSV-1 G47Δ IN PATIENTS WITH CASTRATION RESISTANT PROSTATE CANCER Hiroshi Fukuhara, Yuta Takeshima, Yukio Homma, Yasushi Ino, and Tomoki Todo Hiroshi FukuharaHiroshi Fukuhara More articles by this author , Yuta TakeshimaYuta Takeshima More articles by this author , Yukio HommaYukio Homma More articles by this author , Yasushi InoYasushi Ino More articles by this author , and Tomoki TodoTomoki Todo More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.399AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Oncolytic herpes simplex viruses type 1 (HSV-1) is an attractive therapeutic agent for treating cancer due to its capacity to selectively replicate in cancer cells, kill them, and spread their progeny to surrounding cancer cells. Recently, FDA approved IMLYGIC™ (Talimogene laherparepvec) as the first oncolytic virus drug in developed countries. IMLYGIC is a second-generation oncolytic HSV-1 that showed a higher durable response rate and a better overall survival in the group of advanced malignant melanoma patients than the control group. G47Δ used in this study is a third-generation oncolytic HSV-1 that has triple mutations in the γ34.5, α47 and ICP6 genes. In our preclinical studies, G47Δwas effective in inhibiting the growth of prostate cancer even after having switched to castration resistant. The clinical-grade G47Δ was manufactured at the GMP Vector Production Facility at the Institute of Medical Science, the University of Tokyo. The quality tests were performed extensively under GLP at four steps of manufacture. METHODS Based on the preclinical data, the protocol for the first clinical trial of oncolytic virus therapy against prostate cancer in Japan was designed. In this single-armed phase I study, patients with prostate cancer that had not received prostatectomy and recurred after hormonal therapy, with or without prior record of chemotherapy and with or without remote metastases, are included. G47Δ is injected directly into the prostate by a transrectal ultrasound-guided transperineal technique. The primary endpoint is to assess the safety of G47Δ. A dose escalation is planned in 3 cohorts with 3 subjects per cohort; G47Δ (3 x 108 pfu) is administered twice in the first cohort, three times in the second, and four times in the third. RESULTS The protocol was approved by IRB for gene therapy at the University of Tokyo in September 2011. The applications for the gene therapy clinical protocol and for the use of recombinant bioorganisms for clinical purposes were both approved by the government in August 2012, and the first patient was registered in May 2013. We have currently advanced to the third cohort. So far, the treatment has been well tolerated by the patients, and no severe adverse events attributable to G47Δ have been observed. The current status and recent data of this clinical trial will be presented. CONCLUSIONS In a phase 1 study of a third-generation oncolytic HSV-1 G47Δ in patients with castration resistant prostate cancer, the treatment has been well tolerated by the patients and no severe adverse events attributable to G47Δ have been observed so far. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e658-e659 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Hiroshi Fukuhara More articles by this author Yuta Takeshima More articles by this author Yukio Homma More articles by this author Yasushi Ino More articles by this author Tomoki Todo More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...