Pd48-01 Efficacy of Nadofaragene Firadenovec-VNCG for Patients With Bacillus Calmette-Guérin-Unresponsive Non-Muscle-Invasive Bladder Cancer: Final Results From a Phase 3 Trial

You have accessJournal of UrologyBladder Cancer: Non-invasive III (PD48)1 May 2024PD48-01 EFFICACY OF NADOFARAGENE FIRADENOVEC-VNCG FOR PATIENTS WITH BACILLUS CALMETTE-GUÉRIN-UNRESPONSIVE NON-MUSCLE-INVASIVE BLADDER CANCER: FINAL RESULTS FROM A PHASE 3 TRIAL Stephen A. Boorjian, Vikram M. Narayan, Badrinath R. Konety, Viraj A. Master, Neal D. Shore, Ashish M. Kamat, Trinity J. Bivalacqua, Max R. Kates, Jeffrey S. Montgomery, Seth P. Lerner, Paul L. Crispen, Gary D. Steinberg, Piyush K. Agarwal, Anne K. Schuckman, Robert S. Svatek, Brian R. Lane, Lawrence I. Karsh, Marc A. Bjurlin, Gordon A. Brown, Yair Lotan, Brant A. Inman, Michael B. Williams, Michael S. Cookson, Sam S. Chang, Eric H. Kim, Alexander I. Sankin, Dorte Rehm, Jørn S. Jakobsen, Kristian Juul, and Colin P. N. Dinney Stephen A. BoorjianStephen A. Boorjian , Vikram M. NarayanVikram M. Narayan , Badrinath R. KonetyBadrinath R. Konety , Viraj A. MasterViraj A. Master , Neal D. ShoreNeal D. Shore , Ashish M. KamatAshish M. Kamat , Trinity J. BivalacquaTrinity J. Bivalacqua , Max R. KatesMax R. Kates , Jeffrey S. MontgomeryJeffrey S. Montgomery , Seth P. LernerSeth P. Lerner , Paul L. CrispenPaul L. Crispen , Gary D. SteinbergGary D. Steinberg , Piyush K. AgarwalPiyush K. Agarwal , Anne K. SchuckmanAnne K. Schuckman , Robert S. SvatekRobert S. Svatek , Brian R. LaneBrian R. Lane , Lawrence I. KarshLawrence I. Karsh , Marc A. BjurlinMarc A. Bjurlin , Gordon A. BrownGordon A. Brown , Yair LotanYair Lotan , Brant A. InmanBrant A. Inman , Michael B. WilliamsMichael B. Williams , Michael S. CooksonMichael S. Cookson , Sam S. ChangSam S. Chang , Eric H. KimEric H. Kim , Alexander I. SankinAlexander I. Sankin , Dorte RehmDorte Rehm , Jørn S. JakobsenJørn S. Jakobsen , Kristian JuulKristian Juul , and Colin P. N. DinneyColin P. N. Dinney View All Author Informationhttps://doi.org/10.1097/01.JU.0001008712.53259.7d.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Prospective clinical trials to evaluate long-term durability of bladder-preserving therapies for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) are limited. Nadofaragene firadenovec-vncg (ADSTILADRIN®) is a novel replication-deficient recombinant adenovirus vector-based gene therapy for high-risk BCG-unresponsive NMIBC with carcinoma in situ (CIS) with/without papillary tumors (± Ta/T1). The phase 3 trial met its primary endpoint as 53.4% (95% confidence interval CI: 43.3, 63.3) of patients achieved a complete response by 3 months. Final outcomes from the 60-month follow-up are reported. METHODS: This open-label, multicenter phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive NMIBC in 2 cohorts: CIS±Ta/T1 (CIS; n=107) and Ta/T1 without CIS (papillary disease PD; n=50). Patients received nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology efficacy assessments. Mandatory biopsies were taken at 12 months, after which patients entered a 4-year follow-up and those remaining high-grade recurrence free (HGRF) were offered continued treatment at the investigator's discretion. RESULTS: For all treated patients, median follow-up was 50.8 months (interquartile range: 39.1, 60.0) with 26.8% of patients receiving 5 or more instillations and 7.6% of patients receiving treatment for at least 57 months. In the efficacy analysis set, 5.8% of patients with CIS and 14.6% of patients with PD were HGRF at month 57. Kaplan-Meier (KM)-estimated HGRF survival rate at 57 months was 13.2% (95% CI: 6.9, 21.5) and 32.7% (19.5, 46.6) in the CIS and PD cohorts, respectively. Within 5 years after the first dose of nadofaragene firadenovec, 40.8% and 29.2% of patients in the CIS and PD cohorts underwent radical cystectomy, respectively. KM-estimated overall survival at 60 months was 76.3% (64.6, 84.5) and 85.9% (70.9, 93.5) in the CIS and PD cohorts, respectively. Four patients with CIS and 1 patient with PD experienced progression to muscle-invasive disease documented by transurethral resection of bladder tumor at the time of high-grade recurrence as collected in the electronic case report form. No new safety signals were identified on long-term follow-up. CONCLUSIONS: Nadofaragene firadenovec provided nearly half of participants with bladder preservation at 60 months and represents a safe intravesical treatment option for patients with BCG-unresponsive CIS±Ta/T1 and Ta/T1 without CIS. Source of Funding: The ongoing follow-up of the phase 3 study is sponsored by Ferring Pharmaceuticals Ltd. The original study was funded by FKD Therapies Oy © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e987 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Stephen A. Boorjian More articles by this author Vikram M. Narayan More articles by this author Badrinath R. Konety More articles by this author Viraj A. Master More articles by this author Neal D. Shore More articles by this author Ashish M. Kamat More articles by this author Trinity J. Bivalacqua More articles by this author Max R. Kates More articles by this author Jeffrey S. Montgomery More articles by this author Seth P. Lerner More articles by this author Paul L. Crispen More articles by this author Gary D. Steinberg More articles by this author Piyush K. Agarwal More articles by this author Anne K. Schuckman More articles by this author Robert S. Svatek More articles by this author Brian R. Lane More articles by this author Lawrence I. Karsh More articles by this author Marc A. Bjurlin More articles by this author Gordon A. Brown More articles by this author Yair Lotan More articles by this author Brant A. Inman More articles by this author Michael B. Williams More articles by this author Michael S. Cookson More articles by this author Sam S. Chang More articles by this author Eric H. Kim More articles by this author Alexander I. Sankin More articles by this author Dorte Rehm More articles by this author Jørn S. Jakobsen More articles by this author Kristian Juul More articles by this author Colin P. N. Dinney More articles by this author Expand All Advertisement PDF downloadLoading ...