(UroToday.com) The 2025 GU ASCO annual meeting featured a urothelial carcinoma trials in progress session and a presentation by Dr. Sandeep Reddy discussing ResQ132A, a phase 2 trial of intravesical gemcitabine + N-803 versus intravesical N-803 and BCG for intermediate-risk non-muscle invasive papillary bladder cancer (NMIBC). In the phase 2/3 study QUILT-3.032, a complete response rate of 71% was observed with combined intravesical use of the IL-15 receptor agonist fusion molecule N-803 (nogapendekin alfa inbakicept, NAI; ANKTIVA) and BCG in cohort A participants with BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease.1 In cohort B participants with high-grade Ta/T1 papillary disease, disease-free survival probability was 55.4% at 12 months. Based on these findings, the combination of N-803 (ANKTIVA) plus BCG is approved by the FDA for BCG-unresponsive NMIBC CIS +/- Ta/T1 papillary disease.
Due to the ongoing shortage of BCG, gemcitabine has been increasingly used for first-line NMIBC therapy. N-803’s ability to activate natural killer and CD8+ T cells, thus the innate immune system, to establish T cell memory suggests its potential to enhance efficacy of not only BCG, but also other therapeutics such as gemcitabine:
In the ResQ312A trial, the efficacy of N-803 plus BCG will be compared to N-803 plus gemcitabine in participants with BCG-naïve intermediate-risk papillary NMIBC. Adult participants with histologically-confirmed BCG-naïve intermediate-risk papillary Ta/T1 NMIBC will be enrolled into either Arm A or B. Up to 10 participants will be enrolled in each arm:
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 complete response (absence of any grade papillary NMIBC or CIS disease) rate at month 3 as determined by assessment of cystoscopy, cytology, and biopsy, summarized by the number and percent and exact 95% CI using the Clopper-Pearson method. Secondary endpoints are progression-free survival, time to disease progression, overall survival, disease-specific survival, duration of response and cystectomy avoidance rate, to be analyzed using Kaplan-Meier methods. Safety will be assessed, including adverse events and serious adverse events.
Presented by: Sandeep Reddy, MD, ImmunityBio, Inc., San Diego, CA
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2025 Genitourinary (GU) American Society of Clinical Oncology (ASCO) Annual Meeting, San Francisco, CA, Thurs, Feb 13 – Sat, Feb 15, 2025.
Related content: ResQ132A Trial Examines N-803 Combinations for Intermediate-Risk Bladder Cancer Treatment - Bobby Reddy
References:
- Chamie K, Chang SS, Kramolowsky E, et al. IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer. NEJM Evid 2022; 2(1)