Prolonged Progression-Free Survival, Disease-Free Survival and Cystectomy Avoidance with IL-15 Receptor Lymphocyte-Stimulating Agent NAI plus BCG in BCG-Unresponsive Papillary-Only NMIBC

Abstract

Purpose: In QUILT-3.032, the efficacy of IL-15 receptor agonist, nogapendekin alfa inbakicept (NAI) in combination with BCG for BCG-unresponsive high-grade papillary-only non-muscle invasive bladder cancer (NMIBC) was assessed. Herein we report the 36-month follow-up among participants with BCG-unresponsive papillary disease (Cohort B).

Materials and methods: NCT03022825 is an open-label, multi-center study with BCG-unresponsive high-grade Ta/T1 papillary NMIBC who received 400μg NAI plus 50mg BCG intravesically weekly for six consecutive weeks. The primary endpoint 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 (TRAEs) 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 TRAEs were grade 1-2 (61%) with 3% grade 3, and no grade 4-5.

Conclusions: The 12- 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.

Keywords: BCG-unresponsive; N-803; papillary NMIBC.