Treatment with intravesical Bacille Clamette-Gúerin (BCG) with novel IL15 superagonist, N-803, demonstrated promising safety and efficacy which exceeded that of existing treatment options for patients with BCG-unresponsive non–muscle-invasive bladder cancer, according to findings from a an open-label, 3 cohort, multicenter study presented at the ASCO Annual Meeting.

“N-803… is a mutant IL-15-based immunostimulatory fusion protein complex that promotes proliferation and activation of natural killer cells and CD8+ T cells, but not regulatory T cells,” explained Karim Chamie, MD, University of California-Los Angeles, and colleagues.

In a previous Phase 1b trial, all BCG-naïve patients with non–muscle-invasive bladder cancer treated with N-803 with BCG achieved complete response with no recurrences for the study duration of 24 months.

In this study, 160 patients with BCG-unresponsive high-grade NMIBC received BCG plus N-803. Of the total patients, 83 had non–muscle-invasive bladder carcinoma in situ (CIS) and 77 had papillary carcinoma. For those patients with CIS, the primary end point was incidence of complete response (CR) of CIS at any time. For those with papillary carcinoma, the primary end point was disease-free survival (DFS) at 12 months.  

For patients with CIS, the CR rate was 71% and the median duration of CR was 24.1 months for those who responded. Additionally, 91% of patients with CIS avoided cystectomy and 96% achieved bladder cancer specific progression free survival at 24 months. For the patients with papillary carcinoma, there was DFS rate of 57% at 12 months and 48% at 24 months, and 95% avoided cystectomy. For patients who responded, the median time to cystectomy was 12.9 months, compared to 7.8 months in non-responders.

There was a 99% bladder cancer specific overall survival at 2 years. For over 90% of patients, cystectomy was avoided with 2 years of follow-up.

Dr Chamie and colleagues also reported that N-803 activity was confined to the bladder. The most common low grade adverse events (AEs) included dysuria, pollakiuria, hematuria, fatigue, and urgency. There were no treatment-related Grade 4 or 5 AEs and no severe AEs were determined to be treatment-related.

With the results of this trial, treatment with novel IL-15 superagonist plus BCG exceeds the efficacy and safety profiles of other available options for patients with BCG-unresponsive non–muscle-invasive bladder cancer.

Source:

Chamie K, Chang S, Gonzalgo M, et al. Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). Presented at: ASCO Annual Meeting; June 3-7, 2022. Chicago, IL. Abstract 4508.