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Subgroup analyses of the phase 3 study of intravesical nadofaragene firadenovec in patients with high-grade, BCG-unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)

  • Narayan V.,
  • Boorjian S.,
  • Alemozaffer M.,
  • Konety B.R.,
  • Gomella L.,
  • Kamat A.M.,
  • Lerner S.P.,
  • Svatek R.S.,
  • Karsh L.,
  • Canter D.,
  • Lotan Y.,
  • Inman B.A.,
  • Yang M.,
  • Garcia-Horton V.,
  • Sawutz D.,
  • Parker N.,
  • Dinney C.P.N.

Introduction & Objectives

Despite optimal treatment (tx), >50% of NMIBC patients (pts) with initial response to BCG will experience recurrence and progression. With limited tx options, there is an unmet medical need for local, effective, bladder-preserving tx options. Nadofaragene firadenovec is a non-replicating recombinant type 5 adenovirus vector-based gene therapy that delivers a copy of the human IFNα2b gene. The Phase 3 study that assessed its safety and efficacy in 157 pts with high-grade (HG), BCG-unresponsive NMIBC. The study met its primary endpoint with 53.4% of CIS±Ta/T1 pts achieving a complete response (CR), all by 3 months (mos). 43.6% of these pts remained free of HG recurrence at 15 mos.

Materials & Methods

The efficacy analysis included 151 pts: CIS±Ta/T1 (carcinoma in situ with or without HG Ta or T1; n=103) and HG Ta/T1 (HG Ta or T1 without concomitant CIS; n=48).  Nadofaragene (3×1011 vp/mL [75 mL]) was administered once every 3 mos for up 4 doses, with additional dosing at the investigator’s discretion. The protocol mandated a 5-site (dome, trigone, right and left lateral walls, posterior wall) biopsy at 12 mos. Subgroup and multivariate analyses were conducted to assess the baseline (BL) pts characteristics and clinical factors that may contribute to response and durability of response. The subgroup analyses were based on the efficacy population for the following subgroups: age group (<70 or ≥70 yrs); sex; disease status at baseline (BCG-refractory or BCG-relapsed); prior lines of tx (0 or ≥1); prior non-BCG regimens (≤3 or >3); prior courses of BCG (≤3 or >3)


At BL, median age was 70.8 yrs, 82.2% male. Median prior lines of tx, non-BCG regimen, and courses of BCG, were 3, 0, and 2, respectively. For both cohorts, there were no significant differences in response rates at 3 and 15 mos between males and females, age groups, BCG-refractory vs. BCG-relapsed, ≤3 or >3 prior lines of tx, 0 or ≥1 prior non-BCG regimens, and ≤3 or >3 prior courses of BCG. There were also no significant differences between the subgroups in response duration, except in the CIS±Ta/T1 cohort, where patients who had received ≤3 prior courses of BCG had significantly longer response duration vs pts with >3 courses (12.68 vs 4.96 mos; p=0.0172). Results from multivariable analysis confirmed that none of these BL characteristics or prior tx significantly contributed to response rates at 3 and 15 mos or response duration.


These results demonstrate the efficacy of nadofaragene firadenovec regardless of pt characteristics or prior tx history. Nadofaragene firadenovec represents a potential novel tx option for pts with HG BCG-unresponsive NMIBC that advances the current tx paradigm. Clinical trial information: NCT02773849

Tags: EAU21