AUA 2020: A Phase III Study to Evaluate the Safety and Efficacy of Intravesical Nadofaragene Firadenovec for Patients with High-Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer: Papillary Disease Cohort Results

( 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 and are at risk for tumor recurrence and progression. For many years, there have been very limited options for these patients. Radical cystectomy has remained the gold standard through numerous approaches including intravesical and systemic therapies have been investigated.  One of the alternatively to radical cystectomy in patients with BCG-unresponsive NMIBC is nadofaragene firadenovec, a novel intravesical gene-mediated therapy that delivers the human IFNα2b gene resulting in sustained IFNα2b expression, and provided durable responses in a previous Phase 2 trial. In a podium presentation at the American Urologic Association Virtual Annual Meeting, Stephen Boorjian, MD, and colleagues presented results of the papillary disease (PD) cohort of the phase 3 trial of nadofaragene firadenovec.

The authors, through the auspices of the SUO CTC, conducted a multicenter, open-label Phase 3 study investigating nadofaragene for high-grade NMIBC (carcinoma in situ [CIS ± Ta/T1], or PD [Ta/T1 alone]) unresponsive to BCG (NCT02773849). This presentation reports on the data of the papillary disease subset of the study cohort.

Nadofaragene (3X1011 vp/mL [75 mL]) was administered intravesically once every 3 months for up 4 doses in the initial 12 months. Patients without evidence of high-grade disease at month 12 were offered continued treatment at the investigator’s discretion. While the primary outcome was complete response rate (CR) among patients with CIS which has previously been reported, key secondary endpoints included rate and durability of high-grade-recurrence-free (HGRF) survival as well as safety in PD patients.

In the overall study population, a total of 157 patients were enrolled, of whom 50 were in the PD cohort (safety population n=50; efficacy population n=48). At study entry, all patients were BCG-unresponsive. 

Of the 48 patients in the efficacy PD population, 35 (72.9%), 30 (62.5%), 28 (58.3%), and 21 (43.8%) achieved high grade recurrence free survival at months 3, 6, 9, and 12, respectively. 

Within this PD cohort, the most common treatment-emergent adverse events were transient in nature; specifically, instillation site discharge 30%; bladder spasm 18%; micturition urgency 18%; urinary tract infection 18%. Grade 3 treatment-emergent adverse events were reported in 9 patients, of which 3 were deemed study drug-related, with a single Grade 4 (not related to study drug). There were no grade 5 adverse events. 

These data provide encouraging results demonstrating the potential for nadofaregene firadenovec as a treatment option for patients with high-grade BCG-unresponsive NMIBC.

Presented by: Stephen Boorjian, MD, Mayo Clinic, Rochester, MN 

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center. @WallisCJD on Twitter at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020

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

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