ASCO GU 2020: Safety and Efficacy of Nadofaragene Firadenovec (Adstiladrin®), an Intravesical Gene Therapy for the Treatment of High-grade BCG Unresponsive NMIBC

San Francisco, California ( For patients with BCG unresponsive non-muscle invasive bladder cancer, the standard of care for patients who are operative candidates is a radical cystectomy. However, not all patients may be cystectomy candidates, often for a multitude of reasons, including coexisting comorbidities as well as personal considerations and quality of life.1 Thus, there is an unmet need in this space for better local or systemic therapies which may prevent progression of bladder cancer to muscle-invasive or metastatic disease.

A number of intravesical chemotherapies have been evaluated for salvage therapy after BCG failure including gemcitabine, valrubicin, epirubicin, and docetaxel.2 However, there is significant controversy over the efficacy of these agents as many trials were conducted prior to our current standard of care BCG treatment schedules including maintenance BCG, and many did not risk-stratify patients refractory to BCG. Lastly, almost all were single-arm efficacy trials and it is uncertain if any of these agents were superior to repeat BCG. 

Most recently, the FDA approved pembrolizumab for the treatment of patients BCG unresponsive, high-risk, non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. This was based on KEYNOTE-057,3 a single-arm study of 148 patients with high-risk non–muscle-invasive bladder cancer, 96 of whom had BCG-unresponsive carcinoma in situ with or without papillary tumors. In this study, the complete response rate was 41% and the median response duration was 16.2 months, with 24% of patients overall experiencing a complete response lasting at least 12 months.

This study evaluates a novel therapy for the same patient population as KEYNOTE-057, patients with high-grade, BCG unresponsive non-muscle invasive bladder cancer (NMIBC). Nadofaragene firadenovec (rAd-IFN/Syn3) is a replication-deficient recombinant adenovirus gene transfer vector. Interferon-alpha is thought to have both TRAIL-mediated and non-TRAIL mediated cytotoxic effects but single-agent interferon is thought to be ineffective due to inadequate exposure to the urothelium. Nadofaragene firadenovec overcomes this deficiency by using the bladder as a “bioreactor” to increase the production of the interferon protein, enhancing the exposure to the urothelium and thus enhancing cytotoxicity.


Data on 157 patients were presented.


For patients with CIS (n=103), 53.4% achieved a complete response by 3 months, and 24% remained free of high-grade recurrence by 1 year.


For patients with high-grade Ta/T1, 43% of patients were free from recurrence at 1 year.


The most common adverse events were installation site discharge (33%), fatigue (23%), bladder spasm (19.7%), urgency (18%), and hematuria (17%).



Intravesical nadofaragene firadenovec is active and safe for patients with BCG refractory NMIBC. About 24% of all patients remained free of high-grade recurrence at 1 year and this is quite similar to the data presented above on pembrolizumab. Long term follow up is necessary to determine the durability of this therapy.

Presented by: Stephen A. Boorjian, MD, Urologist, Mayo Clinic, Rochester, Minnesota

Written by: Jason Zhu, MD. Medical Oncologist, Division of Genitourinary Cancers, Levine Cancer Institute Twitter: @TheRealJasonZhu at the 2020 Genitourinary Cancers Symposium, ASCO GU #GU20, February 13-15, 2020, San Francisco, California


  1. Kamat AM, Colombel M, Sundi D, et al. BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG. Nature Reviews Urology 2017;14:244-55.
  2. Chehroudi AC, Black PC. Emerging intravesical therapies for the management of bacillus Calmette–Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer: Charting a path forward. Canadian Urological Association Journal 2020;14.
  3. Balar AV, Kulkarni GS, Uchio EM, et al. Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG). American Society of Clinical Oncology; 2019.