Background: Patients (pts) with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) are at significant risk for disease recurrence and progression. While cystectomy can be curative, many such pts are unwilling or unable given the attendant morbidity of surgery. To date, effective salvage intravesical therapies in this setting remain lacking. Nadofaragene firadenovec is a novel intravesical gene-mediated therapy that delivers the human IFNα2b gene resulting in IFNα2b expression that provided durable responses in a previous Phase 2 trial. Herein, we report the results from a follow-up Phase III trial of this agent for pts with BCG unresponsive NMIBC.
Methods: This multicenter, open-label Phase 3 study investigated nadofaragene for high-grade NMIBC (CIS ± Ta/T1, or Ta/T1 alone) unresponsive to BCG. Nadofaragene (3X1011 vp/mL [75 mL]) was administered once every 3 months for up 4 doses in the initial 12 months, with additional dosing at the investigator’s discretion. The primary endpoint was complete response (CR) at any time in pts with carcinoma in situ (CIS).
Results: A total of 157 pts (safety population, n=157; efficacy population, n=151) were enrolled. Among pts with carcinoma in situ (CIS) (n=103), 55 (53.4%) (95% confidence interval [CI], 43.3-63.3) achieved complete response (CR), all by month 3 after treatment. Of these 55 CIS CR pts, 25 (45.5%) remained free of high-grade recurrence at month 12, confirmed on protocol-mandated biopsy. For pts with HG Ta/T1 alone, 35 (72.9%) and 21 (43.8%) were free from recurrence at 3 and 12mos, respectively. Most treatment-emergent adverse events (TEAEs) were transient in nature: instillation site discharge 33.1%; fatigue 23.6%; bladder spasm 19.7%; micturition urgency 17.8%; hematuria 16.6%. There were 2 Gr4 TEAEs (sepsis and anaphylactic reaction, neither related to study drug) and no Gr5 TEAEs.
Conclusions: Nadofaragene achieved CR in 53.4% of pts with BCG-unresponsive CIS, and was well tolerated. Responses were noted early and remained durable to one year. These data represent a potentially significant management advancement for a historically difficult to treat disease state.
Clinical trial information: NCT02773849
Research Funding: FKD Therapies Oy.
Read the Full Clinical Trial: A Phase III, Open Label Study to Evaluate the Safety and Efficacy of INSTILADRIN® (rAd-IFN)/Syn3) Administered Intravesically to Patients With High Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)
Clinical trial information: NCT02773849
Authors: Stephen A. Boorjian, MD, Colin P.N. Dinney, MD; Mayo Clinic, Rochester, Minnesota; The University of Texas MD Anderson Cancer Center, Houston, Texas
Research Funding: FKD Therapies Oy.
Read the Full Clinical Trial: A Phase III, Open Label Study to Evaluate the Safety and Efficacy of INSTILADRIN® (rAd-IFN)/Syn3) Administered Intravesically to Patients With High Grade, BCG Unresponsive Non-Muscle Invasive Bladder Cancer (NMIBC)