Phase 2 trial of immuno-ablation with intrabladder injection of N-803 or intravesical N-803 plus BCG for intermediate-risk non-muscle invasive papillary bladder cancer.

TPS905 Background: Response rates (55-65%) with bacillus Calmette-Guerin (BCG) monotherapy in papillary non-muscle invasive bladder cancer (NMIBC) are lower than rates (70-75%) for carcinoma in situ (CIS) disease, pointing to an unmet need for efficacious treatment of papillary NMIBC. We previously reported a complete response (CR) rate of 71% with combined intravesical use of the interleukin-15 (IL-15) superagonist fusion molecule N-803 (nogapendekin alfa inbakicept, NAI; ANKTIVA) and BCG in QUILT 3.032 cohort A study participants with BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease and a disease-free survival (DFS) probability of 55.4% at 12 months for cohort B participants with BCG-unresponsive high-grade Ta/T1 papillary NMIBC. Based on these and other findings, the combination of N-803 plus BCG was recently approved by the FDA for BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease. In a planned study, the efficacy of intrabladder N-803 immunoablative monotherapy by peritumoral injection of N-803 will be compared to intravesical N-803 plus BCG in patients with intermediate-risk BCG-naïve papillary NMIBC. The rationale for injection is based on findings from pre-clinical murine tumor models, the hypothesis that N-803 half-life will be extended by injection, and the suitability of injection for papillary disease. Methods: In the open-label phase 2 randomized study QUILT-215, adult participants with histologically-confirmed BCG-naïve intermediate-risk papillary Ta/T1 NMIBC will be enrolled into either Arm A or B. Up to 20 participants will be enrolled in each arm. In the first treatment period, Arm A participants will receive 400 µg N-803 monotherapy every 3 weeks by peritumoral intrabladder delivery and Arm B participants will receive 400 µg N-803 plus 50 mg BCG weekly for 6 weeks by intravesical delivery. The initial response assessment will be at 3 months. The second treatment period would commence at the end of month 3 and continue through month 15, with treatment depending upon the month 3 response. The primary endpoint is the CR (absence of any grade papillary NMIBC or CIS disease) rate at month 3 as determined by Investigator assessment of cystoscopy, cytology, and biopsy. The CR rate will be summarized by the number and percent and exact 95% CI using the Clopper-Pearson method. Secondary endpoints are progression-free survival (PFS), time to disease progression, overall survival (OS), disease-specific survival (DSS), duration of response (DOR) and cystectomy avoidance rate, to be analyzed using Kaplan-Meier methods. Safety will be assessed, including adverse events (AEs) and serious AEs (SAEs).