Introduction and objective
Patients (pts) with high-grade (HG) non-muscle invasive bladder cancer (NMIBC) who develop BCG-unresponsive disease are faced with limited therapeutic options. Nadofaragene firadenovec is a novel gene-mediated therapy that confers the human IFNα2b gene to bladder urothelium following intravesical instillation and results in prolonged, localized expression of IFNα2b. Phase 3 primary efficacy, safety, and durable responses were demonstrated in the published, initial findings. Herein, 24 month (mos) follow-up data are presented for the HG Ta/T1 cohort.
Methods
A multicenter, open-label Phase 3 trial enrolled pts into two cohorts with BCG-unresponsive NMIBC: carcinoma in situ (CIS±Ta/T1) and HG Ta/T1 alone. For the Ta/T1 cohort, 48 pts and 50 were included in the efficacy and safety analyses. Nadofaragene (3×1011 vp/mL [75 mL]) was administered once every 3 mos for up to 4 doses. The protocol mandated a 5-site (dome, trigone, right and left lateral walls, posterior wall) biopsy at 12 mos. All pts with an absence of HG disease recurrence at 12 mos were offered continued treatment once every 3 mos at the investigator’s discretion. Pts who did not continue treatment beyond 12 mos were followed.
Results
As of the September 2020 data cutoff, 9/48 (18.8%) pts had received 24 mos of treatment, and 33/48 (68.8%) remained on study with restricted-mean follow-up of 23.5 mos (95% CI 22.9-24.1). Of 48 pts, 35 (72.9%), 21 (43.8%), 16 (33.3%) were HGRF at 3, 12, and 24 mos. Of those HGRF at 3 mos, 16/35 (45.7%) were HGRF at 24 mos and the median duration of HGRFS was 19.8 months. Cystectomy-free survival was 69.8% (95% CI 54.3-80.9) and overall survival was 93.2% (95% CI 80.4–97.8) when estimated via KM at 24 mos, with 11/48 (22.9%) pts having underwent cystectomy. The most common drug-related adverse events (AEs) were 26% instillation site discharge, 16% dysuria, 14% bladder spasm, and 14% micturition urgency. The majority were Grades 1/2. One (2%) pt had any AE leading to discontinuation. There was one Grade 4 AE (not related to study drug/procedure) and no adverse events occurred leading to pt death.
Conclusions
Nadofaragene firadenovec was well tolerated and demonstrates durability of response in pts with HG Ta/T1, BCG-unresponsive NMIBC in 24 mos follow-up after first intravesical treatment. Clinical trial information: NCT02773849.
Source of Funding
FKD Therapies Oy