A First in Human Phase 1 Study of CG0070, a GM-CSF Expressing Oncolytic Adenovirus, for the Treatment of Nonmuscle Invasive Bladder Cancer

No AccessJournal of UrologyInvestigative Urology1 Dec 2012A First in Human Phase 1 Study of CG0070, a GM-CSF Expressing Oncolytic Adenovirus, for the Treatment of Nonmuscle Invasive Bladder Cancer James M. Burke, Donald L. Lamm, Maxwell V. Meng, John J. Nemunaitis, Joseph J. Stephenson, James C. Arseneau, Junko Aimi, Seth Lerner, Alex W. Yeung, Troy Kazarian, Daniel J. Maslyar, and James M. McKiernan James M. BurkeJames M. Burke Billings Clinic, Billings, Montana , Donald L. LammDonald L. Lamm University of Arizona, Phoenix, Arizona , Maxwell V. MengMaxwell V. Meng University of California-San Francisco, San Francisco, California , John J. NemunaitisJohn J. Nemunaitis Mary Crowley Medical Research Center, Dallas, Texas , Joseph J. StephensonJoseph J. Stephenson Cancer Centers of the Carolinas, Greenville, South Carolina , James C. ArseneauJames C. Arseneau Albany Regional Cancer Center, Albany, New York , Junko AimiJunko Aimi Cell Genesys, Inc., South San Francisco, California , Seth LernerSeth Lerner Baylor College of Medicine, Houston, Texas , Alex W. YeungAlex W. Yeung Cell Genesys, Inc., South San Francisco, California , Troy KazarianTroy Kazarian Cell Genesys, Inc., South San Francisco, California , Daniel J. MaslyarDaniel J. Maslyar Cell Genesys, Inc., South San Francisco, California , and James M. McKiernanJames M. McKiernan Columbia University, New York, New York View All Author Informationhttps://doi.org/10.1016/j.juro.2012.07.097AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: We assessed the safety, pharmacokinetics and anticancer activity of intravesical CG0070, a cancer selective, replication competent adenovirus, for the treatment of nonmuscle invasive bladder cancer. Materials and Methods: A total of 35 patients received single or multiple (every 28 days × 3 or weekly × 6) intravesical infusions of CG0070 at 1 of 4 dose levels (1 × 1012, 3 × 1012, 1 × 1013 or 3 × 1013 viral particles). Response to treatment was based on cystoscopic assessment and biopsy or urine cytology. Urine and plasma CG0070, and granulocyte-monocyte colony-stimulating factor were measured in all patients. A subset of 18 patients was assessed for retinoblastoma phosphorylation status. Results: Grade 1–2 bladder toxicities were the most common adverse events observed. A maximum tolerated dose was not reached. High levels of granulocyte-monocyte colony-stimulating factor were detected in urine after administration in all patients. Virus replication was suggested based on an increase in urine CG0070 genomes between days 2 and 5 in 58.3% of tested patients (7 of 12). The complete response rate and median duration of the complete response across cohorts was 48.6% and 10.4 months, respectively. In the multidose cohorts the complete response rate for the combined groups (every 28 days and weekly × 6) was 63.6% (14 of 22 patients). In an exploratory, retrospective assessment patients with borderline or high retinoblastoma phosphorylation who received the multidose schedules had an 81.8% complete response rate (9 of 11). Conclusions: Intravesical CG0070 was associated with a tolerable safety profile and antibladder cancer activity. Granulocyte-monocyte colony-stimulating factor transgene expression and CG0070 replication were also suggested. References 1 : Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. Cancer J Clin2011; 61: 212. Google Scholar 2 : The T1 bladder tumor. Semin Urol1990; 8: 254. Google Scholar 3 : Management of BCG failures in superficial bladder cancer: a review. 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Google Scholar © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetailsCited byNazmifar M, Williams C, Naser-Tavakolian A, Heard J, Rosser C, Theodorescu D and Ahdoot M (2022) Clinical and Preclinical Therapies for Bladder Cancer Following Bacillus Calmette-Guérin FailureJournal of Urology, VOL. 209, NO. 1, (32-48), Online publication date: 1-Jan-2023.Meng M, Gschwend J, Shore N, Grossfeld G, Mostafid H and Black P (2019) Emerging Immunotherapy Options for bacillus Calmette-Guérin Unresponsive Nonmuscle Invasive Bladder CancerJournal of Urology, VOL. 202, NO. 6, (1111-1119), Online publication date: 1-Dec-2019.Donin N, Lenis A, Holden S, Drakaki A, Pantuck A, Belldegrun A and Chamie K (2016) Immunotherapy for the Treatment of Urothelial CarcinomaJournal of Urology, VOL. 197, NO. 1, (14-22), Online publication date: 1-Jan-2017.So A, Rennie P and Jia W (2012) Intravesical Oncoviral Therapy for Bladder CancerJournal of Urology, VOL. 188, NO. 6, (2039-2040), Online publication date: 1-Dec-2012. Volume 188Issue 6December 2012Page: 2391-2397Supplementary Materials Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.Keywordsurinary bladderurinary bladder neoplasmsdose-response relationshiptoxicityAdenoviridaeimmunologicMetricsAuthor Information James M. Burke Billings Clinic, Billings, Montana Financial interest and/or other relationship with Cell Genesys and Jennerex. More articles by this author Donald L. Lamm University of Arizona, Phoenix, Arizona Financial interest and/or other relationship with Albany Regional Cancer Center. More articles by this author Maxwell V. Meng University of California-San Francisco, San Francisco, California Financial interest and/or other relationship with Cell Genesys. More articles by this author John J. Nemunaitis Mary Crowley Medical Research Center, Dallas, Texas Financial interest and/or other relationship with Gradalis. More articles by this author Joseph J. Stephenson Cancer Centers of the Carolinas, Greenville, South Carolina More articles by this author James C. Arseneau Albany Regional Cancer Center, Albany, New York Financial interest and/or other relationship with Albany Regional Cancer Center. More articles by this author Junko Aimi Cell Genesys, Inc., South San Francisco, California More articles by this author Seth Lerner Baylor College of Medicine, Houston, Texas More articles by this author Alex W. Yeung Cell Genesys, Inc., South San Francisco, California Financial interest and/or other relationship with Cell Genesys. More articles by this author Troy Kazarian Cell Genesys, Inc., South San Francisco, California Financial interest and/or other relationship with Cold Genesys. More articles by this author Daniel J. Maslyar Cell Genesys, Inc., South San Francisco, California Financial interest and/or other relationship with Cell Genesys. More articles by this author James M. McKiernan Columbia University, New York, New York More articles by this author Expand All Advertisement PDF downloadLoading ...