Introduction: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase 1b data in BCG-naïve patients with NMIBC demonstrate that intravesical N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. An open-label, 3 cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. We report data on 160 subjects
Methods: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A (CIS) is incidence of complete response (CR) of CIS at any time. The primary endpoint for Cohort B (Papillary) is disease-free rate (DFS) at 12 months.
Results: To date, 83 patients have enrolled in cohort A, 77 in Cohort B. In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT=4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N=4) is 12.9 months versus 7.8 in non-responders (N=8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; thus activity is confined to the bladder.
Low grade treatment related AEs (grade 1-2) include dysuria (22%) , pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No treatment emergent SAE's were considered treatment related. No immune related SAE's have been seen. Final data will be presented at AUA.
Conclusions: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response and 96% absence of progression to MIBC at 24 months. 53% DFS rate at 18 months in Papillary disease, N-803+BCG efficacy and safety profile exceeds other available intravesical and systemic options. s.