Nadofaragene Firadenovec efficacy sustained across subgroups in BCG-unresponsive NMIBC

December 3, 2020
Jason M. Broderick

A separate analysis presented at SUO assessed the impact of nadofaragene firadenovec on the incidence and time to cystectomy.

The efficacy of the novel intravesical gene-mediated therapy nadofaragene firadenovec was sustained across subgroups of patients with high-grade, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC), according to a poster shared during the 2020 Society of Urologic Oncology (SUO) Annual Meeting.

For their subgroup analysis, the researchers assessed data from a pivotal phase 3 study (NCT02773849) of nadofaragene firadenovec. A separate paper also presented during the meeting examined the incidence and time to cystectomy among patients enrolled in the same pivotal trial.

Overall, the multicenter, open-label, repeat-dose phase 3 study accrued 157 patients with high-grade, BCG-unresponsive NMIBC at 33 clinical sites in the United States. Nadofaragene firadenovec was administered by catheter as a single dose into the bladder. Those patients without recurrence received repeat doses at 3, 6, and 9 months.

In the overall study population of 157 patients, the median age was 71 years, 82% were male, and the median time from initial bladder cancer diagnosis was 18 months. Patients’ disease stages at study entry were CIS only (81 patients), Ta (35 patients), Ta + CIS (21 patients), T1 (15 patients), and T1 + CIS (5 patients). The median number of prior lines of therapy was 3 and the median number of prior BCG courses was 2.

The study met its primary end point with nadofaragene firadenovec achieving a complete response (CR) rate of 53.4% at 3 months in a subgroup of patients with carcinoma in situ with or without concomitant high-grade Ta or T1 disease (CIS ± Ta/T1). The 12-month CR rate was 24.3% and the median duration of CR was 9.69 months in these patients.

The 2 posters presented during the SUO meeting were intended to further examine the extent of nadofaragene firadenovec’s benefit in patients with NMIBC.

Time to cystectomy

Among all patients, the 24-month cystectomy-free survival rate was 64.5%.1 Overall, 40 (26.5%) patients underwent cystectomy, including 30 patients with CIS ± Ta/T1 histology and 10 patients with high-grade Ta/T1 disease. The median time to cystectomy was 8.87 months and 8.31 months, respectively.

The median time to cystectomy among patients achieving a CR in the CIS ± Ta/T1 group was significantly longer than those not reaching CR, at 11.35 months versus 6.36 months, respectively (P =.0432). Among patients with high-grade Ta/T1 histology, those without HG recurrence at month 3 had a median time to cystectomy of 12.42 months compared with 5.31 months in patients who had HG recurrence at that timepoint (P = .0095)

“Nadofaragene firadenovec is an effective bladder-sparing treatment for patients with HG BCG-unresponsive NMIBC as demonstrated by lower rate of cystectomy and longer median time to cystectomy,” lead study author, Vikram M. Narayan, MD, Emory University, Winship Cancer Institute, Atlanta, GA, and coauthors wrote.

Subgroup analyses

Subgroups analyses of the 157 patients showed that response rates in patients in the CIS ± Ta/T1 group or in the high-grade Ta/T1 group did not show significant differences between age groups, males and females, ≤3 or >3 prior lines of therapy, BCG-refractory versus BCG-relapsed, 0 or ≥1 prior non-BCG regimens, and ≤3 or >3 prior courses of BCG.2

For all except 1 subgroup, there were also no significant differences in the subpopulations regarding duration of response. However, in the CIS ± Ta/T1 cohort, the duration of response was significantly longer in patients who had received less than 3 courses of prior BCG (12.68 months) versus those who had received more than 3 courses (4.96 months; P = .0172).

Safety data

The safety analysis for the study included all 157 patients.1 The majority of commonly reported treatment-related adverse events (TRAEs) were short-lived (median duration, 1-2 days). The exception were fatigue and frequency of micturition, with median durations of 11 and 41 days, respectively. TRAEs led to treatment discontinuations in 4 patients.

“Nadofaragene firadenovec represents a potential novel treatment option for patients with high-grade BCG-unresponsive NMIBC that advances the current treatment paradigm,” Narayan et al wrote in their conclusion.


1. Narayan V, Boorjian S, Mehrdad A, et al.Low rate of cystectomy and delayed median time to cystectomy among patients who achieved complete response with nadofaragene firadenovec. 2020 Society of Urologic Oncology Annual Meeting (virtual). December 3-5, 2020. Poster 38.

2. Narayan V, Boorjian S, Mehrdad A. Subgroup analyses of the phase 3 study of intravesical nadofaragene firadenovec in patients with high-grade, BCG-unresponsive nonmuscle invasive bladder cancer (NMIBC). 2020 Society of Urologic Oncology Annual Meeting (virtual). December 3-5, 2020. Poster 23.