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

Abstract

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. 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. 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. 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.