Nadofaragene firadenovec is an intravesical gene therapy approved for use in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer who have carcinoma in situ (CIS) with/without papillary disease (Ta or T1). It is administered every 3 months for as long as the patient maintains a complete response (CR). In the phase 2 and 3 clinical trial program, patients without CR at 3 months were not re-treated with nadofaragene firadenovec; however, many immune therapies do benefit from re-induction of this kind. We report findings from an observational cohort study of patients who underwent re-induction with nadofaragene firadenovec in a real-world setting. Electronic health records from US Specialty Networks private urology practices were used to identify patients with urothelial CIS with/without papillary disease (Ta or T1) who (I) underwent induction with intravesical nadofaragene firadenovec therapy; (II) failed to achieve a CR 3 months after the first dose but subsequently received ≥1 re-induction dose; and (III) had ≥1 follow-up cystoscopy examination. In total, 13 male patients [CIS alone (n=8), CIS + Ta (n=2), CIS + T1 (n=3)], aged (mean) 77.5 years, satisfied the study eligibility criteria. Patients had received a mean of 11 prior BCG doses; other prior therapy included gemcitabine (n=4) and pembrolizumab (n=5). Median follow-up was 379 (range, 135-519) days. After the first re-induction dose (Dose 2) of nadofaragene firadenovec, four patients (30.8%) achieved a CR, including two patients with CIS + T1. Of the patients with a CR, three received subsequent maintenance doses: one patient maintained a CR after Doses 3 and 4; one patient showed disease persistence/recurrence after Dose 4, and one patient progressed to T2a disease 15 months after re-induction. Nine patients experienced treatment failure after first re-induction with nadofaragene firadenovec; two received a second re-induction dose without response. In this real-world cohort, approximately 30% of patients achieved a CR after re-induction with nadofaragene firadenovec, supporting the proof of concept of this approach.
Translational andrology and urology. 2026 May 25 [Epub]
Chad Reichard, Andrew Trainer, Katie Grant, Parisa Asgarisabet, Angele Kotomale, Nadia Foskett, Daniel Shoskes
Urology of Indiana, Greenwood, IN, USA., Nebraska Medicine, Omaha, NE, USA., Cardinal Health Specialty Solutions, Dublin, OH, USA., Ferring SAS, Gentilly, France., Ferring Pharmaceuticals Inc., Parsippany, NJ, USA.