Nadofaragene firadenovec-vncg is a non-replicating adenoviral vector-based gene therapy for BCG-unresponsive carcinoma in situ (CIS) with/without HG Ta/T1). We report outcomes following 5 years of planned follow-up.
This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive NMIBC in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) of Nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high-grade recurrence free (HGRF).
One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (IQR 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. 5.8% (95% CI 2.2-12.2) of patients with CIS and 15% (95% CI 6.1-27.8) of patients with HG Ta/T1 were HGRF at month 57. Kaplan-Meier (KM)-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease.
At 60 months, Nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive NMIBC.
The Journal of urology. 2024 May 05 [Epub ahead of print]
Vikram M Narayan, Stephen A Boorjian, Mehrdad Alemozaffar, Badrinath R Konety, Neal D Shore, Leonard G Gomella, Ashish M Kamat, Trinity J Bivalacqua, Jeffrey S Montgomery, Seth P Lerner, Joseph E Busby, Michael Poch, Paul L Crispen, Gary D Steinberg, Anne K Schuckman, Tracy M Downs, Joseph Mashni, Brian R Lane, Gennady Bratslavsky, Lawrence I Karsh, Michael E Woods, Gordon Brown, Daniel Canter, Adam Luchey, Yair Lotan, Brant A Inman, Michael B Williams, Michael S Cookson, Sam S Chang, Alexander I Sankin, Michael A O'Donnell, David Sawutz, Richard Philipson, Nigel R Parker, Seppo Yla-Herttuala, Dorte Rehm, Jørn S Jakobsen, Kristian Juul, Colin P N Dinney
Department of Urology, Emory University School of Medicine, Atlanta, Georgia., Department of Urology, Mayo Clinic, Rochester, Minnesota., Department of Urology, Kaiser Permanente, Los Angeles, California., Department of Urology, University of Minnesota and Allina Health Cancer Institute, Minneapolis, Minnesota., Carolina Urologic Research Center, Myrtle Beach, South Carolina., Department of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania., Department of Urology, University of Texas MD Anderson Cancer Center, Houston, Texas., Department of Urology, Hospitals of the University of Pennsylvania., Department of Urology, University of Michigan, Ann Arbor, Michigan., Scott Department of Urology, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas., Cancer Centers of the Carolinas, Greenville Hospital System, Greenville, South Carolina., Department of GU Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida., Department of Urology, University of Florida, Gainesville, Florida., Department of Urology, Rush University, Chicago, Illinois., USC Institute of Urology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California., Department of Urology, University of Virginia, Charlottesville, Virginia., Banner MD Anderson Cancer Center, Gilbert, Arizona., Division of Urology, Spectrum Health, Michigan State University College of Human Medicine, Grand Rapids, Michigan., Department of Urology, SUNY Upstate Medical University, Syracuse, New York., The Urology Center of Colorado, Denver, Colorado., Department of Urology, Loyola University Medical Center, Maywood, Illinois., New Jersey Urology, Bloomfield, New Jersey., Georgia Urology, Atlanta, Georgia., West Virginia University Cancer Institute, Morgantown, West Virginia., Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas., Division of Urology, Department of Surgery, Western University, London, ON, Canada., Urology of Virginia, Virginia Beach, Virginia., Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma., Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee., Department of Urology, Montefiore Medical Center, Bronx, New York., Department of Urology, University of Iowa, Iowa City, Iowa., FKD Therapies Oy, Kuopio, Finland., Calliditas Therapeutics, Stockholm, Sweden., AI Virtanen Institute University of Eastern Finland and Science Service Center and Gene Therapy Unit, Kuopio, Finland., Ferring Pharmaceuticals A/S, Copenhagen, Denmark.