NCCN Expands Recommendation for Nadofaragene in BCG-Unresponsive NMIBC

Nadofaragene firadenovec-vncg (Adstiladrin) received a National Comprehensive Cancer Network (NCCN) category 2A recommendation for patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer with papillary tumors (+Ta/T1) without carcinoma in situ (CIS), according to the manufacturer, Ferring Pharmaceuticals, said in a release.^1,2

The agent maintained its category 2A recommendation for patients with CIS with or without papillary tumors (Ta/T1). The prior recommendation for the papillary-only indication had been category 2B.

Nadofaragene firadenovec-vncg is an FDA-approved non-replicating intravesical gene-therapy for the treatment of adult patients with high-risk BCG-unresponsive NMIBC CIS with or without papillary tumors (±Ta/T1), and is dosed once every three months.

The agent is not approved by the FDA for BCG-unresponsive NMIBC with high-grade papillary Ta or T1 tumors without CIS, and the safety and effectiveness of nadofaragene firadenovec-vncg for BCG-unresponsive NMIBC with high-grade papillary Ta or T1 only tumors without CIS has not been established.

For patients with high-risk NMIBC, intravesical BCG is recommended as the first-line standard-of-care,³ yet many patients become unresponsive or experience recurrence, leaving limited effective treatment options.¹

Phase 3 Trial and Follow Up

The expanded recommendation is supported by a 5-year follow-up trial (NCT02773849) that evaluated 157 patients with BCG-unresponsive NMIBC in 2 cohorts.

Cohort 1 was CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50).4 In the efficacy analysis, 151 patients were evaluated. Within the treated population, 27% received five or more instillations, while 7.6% continued therapy for 57 months or longer.

At the 57-month mark, the high-grade recurrence-free rate was 5.8% (95% CI 2.2-12.2) among patients with carcinoma in situ (CIS) and 15% (95% CI 6.1-27.8) among those with high-grade Ta/T1 disease. Kaplan-Meier–estimated high-grade recurrence-free survival at 57 months was 13% (95% CI 6.9-21.5) in the CIS cohort and 33% (95% CI 19.5-46.6) in the Ta/T1 cohort.

The bladder-preserving potential of the regimen was underscored by a cystectomy-free survival rate at 60 months of 49% (95% CI 40.0-57.1) overall, which was 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% (95% CI 71.0-86.0), with rates of 76% (95% CI 64.6-84.5) for CIS patients and 86% (95% CI 70.9-93.5) for those with Ta/T1 disease.

Notably, progression to muscle-invasive disease was uncommon, occurring in only 5 patients overall, which included 4 with CIS and 1 patient with Ta/T1 disease.

REFERENCES

1. Ferring Announces Update to NCCN Guidelines Expanding Category 2A Recommendation for Nadofaragene Firadenovec-vncg (ADSTILADRIN®) in Patients with BCG-Unresponsive NMIBC. News release. March 19, 2026. Accessed March 20, 2026

2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology-Bladder Cancer. Version 1.2026, March 16, 2026. Accessed March 20, 2026. https://tinyurl.com/2sw4z2zn

3. Lidagoster S, Ben-David R, De Leon B, Sfakianos JP. BCG and Alternative Therapies to BCG Therapy for Non-Muscle-Invasive Bladder Cancer. Curr Oncol. 2024;31(2):1063-1078. Published 2024 Feb 16. doi:10.3390/curroncol31020079

4. 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