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Clinical Trial
. 2024 Jul;212(1):74-86.
doi: 10.1097/JU.0000000000004020. Epub 2024 May 5.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial

Vikram M Narayan  1 , Stephen A Boorjian  2 , Mehrdad Alemozaffar  3 , Badrinath R Konety  4 , Neal D Shore  5 , Leonard G Gomella  6 , Ashish M Kamat  7 , Trinity J Bivalacqua  8 , Jeffrey S Montgomery  9 , Seth P Lerner  10 , Joseph E Busby  11 , Michael Poch  12 , Paul L Crispen  13 , Gary D Steinberg  14 , Anne K Schuckman  15 , Tracy M Downs  16 , Joseph Mashni Jr  17 , Brian R Lane  18 , Thomas J Guzzo  8 , Gennady Bratslavsky  19 , Lawrence I Karsh  20 , Michael E Woods  21 , Gordon Brown  22 , Daniel Canter  23 , Adam Luchey  24 , Yair Lotan  25 , Brant A Inman  26 , Michael B Williams  27 , Michael S Cookson  28 , Sam S Chang  29 , Alexander I Sankin  30 , Michael A O'Donnell  31 , David Sawutz  32 , Richard Philipson  33 , Nigel R Parker  34 , Seppo Yla-Herttuala  34 , Dorte Rehm  35 , Jørn S Jakobsen  35 , Kristian Juul  35 , Colin P N Dinney  7
Affiliations
Clinical Trial

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial

Vikram M Narayan et al. J Urol. 2024 Jul.

Abstract

Purpose: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.

Materials and methods: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer 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) 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 (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-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 nonmuscle-invasive bladder cancer.

Keywords: BCG-unresponsive bladder cancer; bladder cancer; gene therapy; intravesical instillation; nonmuscle invasive bladder cancer.

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