Durable Responses and Cystectomy Avoidance With Interleukin-15 Receptor Agonist NAI Plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer With Carcinoma In Situ ± Papillary Disease.

PURPOSE: We report long-term follow-up on participants in the QUILT-3.032 study in bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle-invasive bladder cancer (NMIBC) carcinoma in situ (CIS) ± papillary disease using nogapendekin alfa inbakicept-pmln (NAI, N-803) approved by the Food and Drug Administration (Anktiva) in combination with BCG.

MATERIALS AND

METHODS

Participants received 400 mcg NAI in combination with 50 mg BCG through intravesical instillation weekly for 6 weeks, with optional reinduction if complete response (CR) was not achieved at month 3. Primary end point was CR rate at any time; secondary end points were duration of CR, progression-free survival, overall survival, 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 duration of CR of 26.6 months (range 0.03-53.62). The Kaplan-Meier estimated cystectomy-free rate 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 were largely grade 1 to 2 (61%), with 3% grade 3 and no grade 4 or 5 treatment-related adverse events 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 cystectomy-free rate 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.