Introduction:
The goals of treatment for NMIBC are to reduce recurrence and prevent progression. However, despite optimal treatment, more than 50% of the patients who demonstrated an initial response to BCG will experience recurrence and progression and become BCG-unresponsive.
With limited treatment options, there is an unmet medical need for local, effective, bladder-preserving treatment 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 assessed its safety and efficacy in 157 patients with high-grade, BCG-unresponsive NMIBC. The study met its primary endpoint with 53.4% of patients with CIS±Ta/T1 achieving a complete response (CR), all by 3 months. 43.6% of these patients remained free of high-grade recurrence at 15 months.
Subgroup and multivariate analyses were conducted to assess the baseline patient characteristics and clinical factors that may contribute to response and durability of response.
Methods:
The multicenter, open-label Phase 3 study enrolled patients into two cohorts: CIS±Ta/T1 (carcinoma in situ with or without high-grade Ta or T1) and high-grade Ta/T1 (High-Grade Ta or T1 without concomitant CIS) with 103 and 48 patients, respectively, included in the efficacy analysis.
Nadofaragene (3x1011 vp/mL [75 mL]) was administered once every 3 months 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 months.
The subgroup analyses were based on the efficacy population for the following subgroups: age group (<70 or ≥70 years); sex; disease status at baseline (BCG-refractory or BCG-relapsed); prior lines of therapy (0 or ≥1); prior non-BCG regimens (≤3 or >3); prior courses of BCG (≤3 or >3)
A multivariate analysis was also conducted for confirmation.
These analyses were based on the data cut-off at 15 months.
Results:
At baseline, patients had median age of 70.8 years, 82.2% were male. The median prior lines of therapy, 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 months between males and females, age groups, BCG-refractory vs. BCG-relapsed, ≤3 or >3 prior lines of therapy, 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 duration of response, except in the CIS±Ta/T1 cohort, where patients who had received ≤3 prior courses of BCG had significantly longer duration of response compared to patients who received >3 courses (12.68 vs. 4.96 months; p=0.0172).
Results from multivariable analysis confirmed that none of these baseline characteristics or prior therapy significantly contributed to response rates at 3 and 15 months or duration of response.
Conclusion:
These results demonstrate the efficacy of nadofaragene firadenovec regardless of patient characteristics or prior treatment history.
Nadofaragene firadenovec represents a potential novel treatment option for patients with high-grade BCG-unresponsive NMIBC that advances the current treatment paradigm.
Clinical trial information: NCT02773849
Funding: FKD Therapies Oy, Finland
Image(s) (click to enlarge):
SUBGROUP ANALYSES OF THE PHASE 3 STUDY OF INTRAVESICAL NADOFARAGENE FIRADENOVEC IN PATIENTS WITH HIGH-GRADE, BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC)
Category
Bladder Cancer > Non-Muscle Invasive Bladder Cancer
Description
Poster #23
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Presented By: Vikram Narayan
Authors:
Vikram Narayan
Stephen Boorjian
Mehrdad Alemozaffer
Badrinath R. Konety
Leonard Gomella
Ashish M. Kamat
Seth P. Lerner
Robert S. Svatek
Lawrence Karsh
Daniel Canter
Yair Lotan
Brant A. Inman
Mindy Yang
Viviana Garcia-Horton
David Sawutz
Nigel Parker
Colin P.N. Dinney