Durable Responses and Cystectomy Avoidance with IL-15 Receptor Agonist NAI plus BCG In BCG-Unresponsive NMIBC with Carcinoma In Situ +/- Papillary Disease

PURPOSE: We report long-term follow-up on participants in the QUILT-3.032 study in BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS) +/- papillary disease utilizing nogapendekin alfa inbakicept (NAI) approved by the FDA (ANKTIVA) in combination with BCG. MATERIALS AND METHODS: Participants received 400 mcg NAI in combination with 50 mg BCG via intravesical instillation weekly for six weeks, with optional re-induction if complete response (CR) was not achieved at month 3. Primary endpoints were CR rate at any time; secondary endpoints were duration of CR (DOR), progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS), and time to cystectomy. RESULTS: The CR rate (n=100) was 71% (95% CI, 61.1, 79.6) with a median DOR of 26.6 months (range, 0.03-53.62). The cystectomy-free rate (CFR) in the 71 responders at 24- and 36-months was 90.3% (95% CI 79.7, 95.6) and 84.2% (95% CI 69.6, 92.1), respectively. DSS was 100% (95% CI 100.0, 100.0) at 12-months, and 98.2% (95% CI 88.2, 99.8) at 36-months. Treatment-related adverse events (TRAE) were largely grade 1 to 2 (61%), with 3% grade 3 and no grade 4 or 5 TRAE observed with this biological combination. CONCLUSIONS: The CR rate and durability of responses that surpass 53 months reveal the efficacy of NAI in combination with BCG for treating BCG-unresponsive NMIBC with CIS +/- Ta/T1 disease. The high CFR of 84% and DSS of 98% at 36-months suggest that NAI plus BCG is a safe and efficacious option for NMIBC with CIS +/- Ta/T1 disease.