Prolonged Progression-Free Survival, Disease-Free Survival, and Cystectomy Avoidance With IL-15 Receptor Lymphocyte–Stimulating Agent NAI Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin–Unresponsive Papillary-Only Nonmuscle-Invasive Bladder Cancer

PURPOSE: In QUILT-3.032, the efficacy of interleukin-15 receptor agonist, nogapendekin alfa inbakicept (NAI), in combination with bacillus Calmette-Guérin (BCG) for BCG-unresponsive high-grade papillary-only nonmuscle-invasive bladder cancer was assessed. In this study, we report the 36-month follow-up among participants with BCG-unresponsive papillary disease (cohort B). MATERIALS AND METHODS: NCT03022825 is an open-label, multicenter study of patients with BCG-unresponsive high-grade Ta/T1 papillary nonmuscle-invasive bladder cancer who received 400 μg NAI plus 50 mg BCG intravesically weekly for 6 consecutive weeks. The primary end point is disease-free survival (DFS) at 12 months. Progression-free survival (PFS), disease-specific survival (DSS), and cystectomy avoidance were assessed. Treatment-related adverse events were assessed. RESULTS: At July 15, 2024, data cutoff, the DFS rates at 12, 24, and 36 months were 58.2% (95% CI: 46.6, 68.2), 52.1% (95% CI: 40.3, 62.7), and 38.2% (95% CI: 25.6, 50.6), respectively. The PFS rates at 12 and 36 months were 94.9% (95% CI: 86.9, 98.0) and 83.1% (95% CI: 69.5, 91.0). The DSS rates at 12 and 36 months were 98.7% (95% CI: 91.4, 99.8) and 96.0% (95% CI: 88.2, 98.7). The median DSS has not been reached. Cystectomy avoidance rates at 12 and 36 months were 92.2% (95% CI: 83.4, 96.4) and 81.8% (95% CI: 68.1, 90.1), with median time to cystectomy not reached. Most treatment-related adverse events were grade 1 to 2 (61%) with 3% grade 3 and no grade 4 to 5. CONCLUSIONS: The 12-month and 36-month DFS, PFS, DSS, and cystectomy avoidance rates demonstrate the effectiveness and safety of NAI plus BCG in the management of BCG-unresponsive papillary disease. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03022825.