IL-15RαFc Superagonist N-803 Yields Strong Response in BCG-Unresponsive Bladder Cancer

Patients with BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) treated with IL-15RαFc superagonist N-803 had a 99% bladder cancer specific overall survival at 2 years, according to final clinical results presented at the 2022 ASCO Annual Meeting (Abstract 4508).

This patient population has limited treatment options, according to study presenter Karim Chamie, MD, of University of California-Los Angeles. N-803 is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RαFc) that promotes proliferation and activation of natural killer cells and CD8+ T cells, but not regulatory T cells.

In this study, Chamie and colleagues treated 160 patients with intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. Two cohorts were examined; cohort A included patients with carcinoma in situ with or without papillary disease (CIS; 83 patients) and cohort B included those with papillary disease (77 patients).

Mean number of prior BCG installations was 16.6 in cohort A and 12.3 in cohort B. Patients had also received prior antibody drug conjugates, systemic immunotherapies, and intravesical chemotherapy. This suggests it was a heavily pretreated cohort.

The treatments were well-tolerated. The rate of treatment-related serious adverse events was 1%. There were no treatment-related deaths or immune-related serious adverse events. Grade-3 toxicities were less than 1%.

Patients with CIS in cohort A had a complete response rate of 71%, with a median duration of response of more than 2 years (26.6 months) in those who have responded. In this cohort, 16% of patients underwent cystectomy with only 9% of responders undergoing cystectomy. The bladder cancer specific progression-free survival was 96.4% up to 2 years. The bladder cancer specific overall survival was 100%.

In the Cohort B, patients with papillary disease had a 55% 12-month disease-free survival rate, and a 48% 24-month disease-free survival rate. The majority (94%) of these patients also avoided cystectomy. The bladder cancer specific overall survival was 99%.