AUA 2021:The Efficacy of Intravesical Nadofaragene Firadenovec for Patients with Carcinoma in Situ (CIS), BCG-Unresponsive Non-Muscle Invasive Bladder Cancer: Longer-Term Follow-up from the Phase III Trial

( Most patients newly diagnosed with bladder cancer have non-muscle invasive disease (NMIBC). For patients with intermediate or high-risk NMIBC and those with carcinoma in situ (CIS), adjuvant treatment with BCG is guideline-recommended on the basis of proven benefits in disease recurrence. While BCG is efficacious, many patients eventually develop BCG-unresponsive disease. Despite guideline-concordant care, many patients with BCG-unresponsive NIMBC are at significant risk for recurrence and progression.

For many years, there have been very limited options for these patients. Radical cystectomy has remained the gold standard even though numerous approaches including intravesical and systemic therapies have been investigated. Nadofaragene firadenovec is a non-replicating recombinant type 5 adenovirus vector-based gene therapy that delivers a copy of the human IFNα2b gene. In a phase III trial, nadofaragene firadenovec treatment was associated with 53.4% of patients with CIS±Ta/T1 achieving a complete response (CR), all within the first 3 months.

In a moderated poster presentation at the American Urologic Association Virtual (AUA) Annual Meeting, Dr. Schuckman and colleagues presented longer-term follow-up in this cohort of patients with CIS±Ta/T1 disease treated with nadofaragene firadenovec.

This open-label Phase 3 study enrolled 107 patients with BCG-unresponsive, CIS±Ta/T1 (CIS with/without HG Ta or T1). The authors report efficacy analysis among 103 patients. Patients received nadofaragene (3x1011 vp/mL [75 mL]) once every 3 months for up to 4 doses. The protocol mandated a 5-site biopsy at 12 months. All patients without evidence of HG recurrence at 12 months were offered continuing treatment once every 3 months at the discretion of the investigators. Those patients who did not receive further treatment had an ongoing observation.


With a data cutoff of September 2020, 62.1% of the cohort remained on study (64/103). The restricted-mean follow of these patients was 23.5 months (95% CI 22.9-24.0) and 18/103 (17.5%) patients had received a full two years (24 months) of therapy.

At 24 months after the first dose, 20/103 (19.4%) patients continued to remain free of HG recurrence. Of the 55 patients who achieved a CR following treatment, 20 (36.4%) remained free of HG recurrence at 24 months and the median duration of HG recurrence-free survival 12.2 months.


By 24 months 33/103 (32%) patients had undergone cystectomy, for a Kaplan Meier cystectomy-free survival of 64.6% (95% CI 54.1-73.3) and overall survival of 94.4% (95% CI 87.0-97.6).

In keeping with prior reports, nadofaragene firadenovec was well tolerated with 1 grade 4 non-treatment-related AE (sepsis) and no grade 5 AEs. The most common drug-related AEs were instillation site discharge (24.3%), fatigue (23.4%), bladder spasm (17.8%), and micturition urgency (16.8%), the majority of which were grade 1 and 2. Two patients (1.9%) discontinued treatment due to drug-related AEs (1 instillation site discharge, 1 bladder spasm).

The authors thus conclude that intravesical nadofaragene firadenovec has sustained durability of response with longer follow-up in patients with high-grade BCG-unresponsive NMIBC.

Presented by: Anne K. Schuckman, MD, Associate Professor of Clinical Urology, USC Keck School of Medicine

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 American Urological Association, (AUA) Annual Meeting, Fri, Sep 10, 2021 – Mon, Sep 13, 2021.

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