The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology for bladder cancer to include nadofaragene firadenovec-vncg (Adstiladrin) as a category 2A recommendation for the treatment of patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with papillary tumors (+Ta/T1) without carcinoma in situ (CIS).1,2
In December 2022, the FDA approved nadofaragene firadenovec as the first gene therapy in patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.3 The regulatory decision was supported by data from the phase 3 Study CS-003 (NCT02773849).
Findings from the 5-year follow-up of Study CS-003 published in the Journal of Urology demonstrated that patients with CIS who received nadofaragene firadenovec (n = 103) achieved a 3-month complete response (CR) or high-grade recurrence-free (HGRF) survival rate of 53.4% (95% CI, 43.4%-63.3%).4 The 3-month CR/HGRF survival rates among patients with high-grade Ta/T1 disease (n = 48) and all patients (n = 151) were 72.9% (95% CI, 58.2%-84.7%) and 59.6% (95% CI, 51.3%-67.5%), respectively.
Nadofaragene Firadenovec Added to NCCN Guidelines in BCG-Unresponsive Papillary NMIBC Without CIS
- The NCCN has updated its Clinical Practice Guidelines in Oncology for bladder cancer to include nadofaragene firadenovec as a category 2A recommendation in BCG-unresponsive NMIBC with papillary tumors without CIS.
- In December 2022, the FDA approved nadofaragene firadenovec as the first gene therapy in patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.
- Findings from the 5-year follow-up of Study CS-003 revealed that patients with CIS who received nadofaragene firadenovec (n = 103) achieved a 3-month CR/HGRF survival rate of 53.4% (95% CI, 43.4%-63.3%).
How was Study CS-003 designed?
Study CS-003 was a single-arm, open-label, repeat dose study that was conducted across 33 sites in the United States. The study enrolled BCG-unresponsive patients with NMIBC into 2 cohorts: the CIS with/without Ta/T1 disease cohort and the Ta/T1 disease cohort. The CIS with/without Ta/T1 disease cohort included patients with CIS with/without concomitant high-grade Ta or T1 NMIBC at diagnosis and the Ta/T1 cohort included patients with Ta or T1 tumors without concomitant CIS.
All patients were treated with nadofaragene firadenovec at 75 mL (3 × 1011 vp/mL) via intravesical administration through a urinary catheter. All patients underwent recurrence evaluation with urine cytology and cystoscopy. If high-grade recurrence did not occur, administration was repeated at months 3, 6, and 9. After the initial 12-month treatment period, patients entered a 4-year follow-up period.
The primary outcome of Study CS-003 was CR rate in the CIS with/without Ta/T1 disease cohort at any time within 12 months after the first dose of nadofaragene firadenovec. Secondary outcomes included overall survival (OS), durability of CR, incidence of HGRF survival, durability of HGRF survival, incidence of cystectomy, cystectomy-free survival, and safety.
What are the additional efficacy and safety data from Study CS-003?
Further efficacy data from Study CS-003 revealed that the median durations of HGRF survival in the CIS, high-grade, and overall cohorts were 5.9 months (95% CI, 3.4-8.3), 12.4 months (95% CI, 6.7-20.3), and 7.3 months (95% CI, 5.7-11.9), respectively. The respective 60-month OS rates were 76% (95% CI, 64.6%-84.5%), 86% (95% CI, 70.9%-93.5%), and 80% (95% CI, 71.0%-86.0%). The median duration of OS was not reached in any group.
In the safety population (n = 157), grade 1 or 2 adverse effects (AEs) occurred at a rate of 66%. Grade 3 AEs were reported at a rate of 3.8%; no grade 4 or 5 study drug–related AEs occurred. The most common grade 1 or 2 study drug–related AEs included discharge around the catheter during instillation (25%), fatigue (20%), bladder spasm (16%), micturition urgency (15%), chills (11%), and dysuria (12%). Grade 3 study drug–related AEs included micturition urgency (1.3%), bladder spasm (0.6%), syncope (0.6%), hypertension (0.6%), and urinary incontinence (0.6%).
References
- Ferring announces update to NCCN guidelines expanding category 2A recommendation for nadofaragene firadenovec-vncg (Adstiladrin) in patients with BCG-unresponsive NMIBC. News release. Ferring Pharmaceuticals. March 19, 2026. Accessed March 20, 2026. https://ferringusa.com/?press=ferring-announces-update-to-nccn-guidelines-expanding-category-2a-recommendation-for-nadofaragene-firadenovec-vncg-adstiladrin-in-patients-with-bcg-unresponsive-nmibc
- NCCN. Clinical Practice Guidelines in Oncology. Bladder cancer, version 1.2026. March 16, 2026. Accessed March 20, 2026. https://www.nccn.org/professionals/physician_gls/pdf/bladder.pdf
- FDA approves first adenoviral vector-based gene therapy for high-risk Bacillus Calmette-Guérin unresponsive non-muscle invasive bladder cancer. FDA. Updated December 19, 2022. Accessed March 20, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-first-adenoviral-vector-based-gene-therapy-high-risk-bacillus-calmette-guerin
- Narayan VM, Boorjian SA, Alemozaffar M, et al. 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. J Urol. 2024;212(1):74-86. doi:10.1097/JU.0000000000004020
