Efficacy of Intravesical Nadofaragene Firadenovec for Patients with BCG-Unresponsive Non-muscle Invasive Bladder Cancer: 5 Year Follow-Up from a Phase 3 Trial

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 Jr; 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

doi:10.1097/JU.0000000000004020

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Efficacy of Intravesical Nadofaragene Firadenovec for Patients with BCG-Unresponsive Non-muscle Invasive Bladder Cancer: 5 Year Follow-Up from a Phase 3 Trial

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Efficacy of Intravesical Nadofaragene Firadenovec for Patients with BCG-Unresponsive Non-muscle Invasive Bladder Cancer: 5 Year Follow-Up from a Phase 3 Trial

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, …

The Journal of urology, Vol.212(1), pp.74-86

07/2024

DOI: 10.1097/JU.0000000000004020

PMCID: PMC12721637

PMID: 38704840

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Abstract

Background: 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. Methods: 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). Results: 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. Conclusions: 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.

Bladder Cancer

Gene Therapy

BCG-unresponsive bladder cancer

non-muscle invasive bladder cancer

intravesical instillation

Details

Title: Subtitle: Efficacy of Intravesical Nadofaragene Firadenovec for Patients with BCG-Unresponsive Non-muscle Invasive Bladder Cancer: 5 Year Follow-Up from a Phase 3 Trial
Creators: Vikram M Narayan - Emory University
Stephen A Boorjian - Mayo Clinic
Mehrdad Alemozaffar - Kaiser Permanente
Badrinath R Konety - University of Minnesota
Neal D Shore - Carolina Urologic Research Center
Leonard G Gomella - Thomas Jefferson University
Ashish M Kamat - The University of Texas MD Anderson Cancer Center
Trinity J Bivalacqua - University of Pennsylvania
Jeffrey S Montgomery - University of Michigan
Seth P Lerner - Baylor College of Medicine
Joseph E Busby - Prisma Health
Michael Poch - Moffitt Cancer Center
Paul L Crispen - University of Florida
Gary D Steinberg - Rush University
Anne K Schuckman - University of Southern California
Tracy M Downs - University of Virginia
Joseph Mashni Jr - Banner MD Anderson Cancer Center
Brian R Lane - Michigan State University
Gennady Bratslavsky - SUNY Upstate Medical University
Lawrence I Karsh - The Urology Center of Colorado
Michael E Woods - Loyola University Medical Center
Gordon Brown - New Jersey Urology
Daniel Canter - Georgia Urology
Adam Luchey - West Virginia University
Yair Lotan - The University of Texas Southwestern Medical Center
Brant A Inman - Western University
Michael B Williams - Urology of Virginia
Michael S Cookson - University of Oklahoma Health Sciences Center
Sam S Chang - Vanderbilt University Medical Center
Alexander I Sankin - Montefiore Medical Center
Michael A O'Donnell - University of Iowa
David Sawutz - FKD Therapies Oy, Kuopio, Finland
Richard Philipson - Calliditas Therapeutics, Stockholm, Sweden
Nigel R Parker - University of Eastern Finland
Seppo Yla-Herttuala - University of Eastern Finland
Dorte Rehm - Ferring Pharmaceuticals
Jørn S Jakobsen - Ferring Pharmaceuticals
Kristian Juul - Ferring Pharmaceuticals
Colin P N Dinney - The University of Texas MD Anderson Cancer Center
Resource Type: Journal article
Publication Details: The Journal of urology, Vol.212(1), pp.74-86
DOI: 10.1097/JU.0000000000004020
PMID: 38704840
PMCID: PMC12721637
NLM abbreviation: J Urol
eISSN: 1527-3792
Language: English
Electronic publication date: 05/05/2024
Date published: 07/2024
Academic Unit: Urology
Record Identifier: 9984622887802771

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