PLLBA-01 FINAL CLINICAL RESULTS OF PIVOTAL TRIAL OF IL-15RΑFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) CIS AND PAPILLARY COHORTS

Abstract

You have accessJournal of UrologyCME1 May 2022PLLBA-01 FINAL CLINICAL RESULTS OF PIVOTAL TRIAL OF IL-15RΑFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) CIS AND PAPILLARY COHORTS Sam Chang, Karim Chamie, Mark Hidalgo, Eugene Kramolowsky, Wade Sexton, Sandeep Reddy, and Patrick Soon-Shiong Sam ChangSam Chang More articles by this author , Karim ChamieKarim Chamie More articles by this author , Mark HidalgoMark Hidalgo More articles by this author , Eugene KramolowskyEugene Kramolowsky More articles by this author , Wade SextonWade Sexton More articles by this author , Sandeep ReddySandeep Reddy More articles by this author , and Patrick Soon-ShiongPatrick Soon-Shiong More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002671.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with NMIBC CIS unresponsive to BCG have limited treatment options. N-803 (Anktiva) is a mutant IL-15-based immunostimulatory fusion protein complex (IL15RaFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Phase 1b data in BCG-naïve patients with NMIBC demonstrate that intravesical N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. An open-label, 3 cohort multicenter study (QUILT 3.032) of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. We report data on 160 subjects. METHODS: All treated patients received intravesical N-803 plus BCG, consistent with the standard induction/maintenance treatment schedule. The primary endpoint for Cohort A (CIS) is incidence of complete response (CR) of CIS at any time. The primary endpoint for Cohort B (Papillary) is disease-free rate (DFS) at 12 months. RESULTS: To date, 83 patients have enrolled in cohort A, 77 in Cohort B. In the overall population, median age is 72.3 years, 81% male, with mean number of prior TURBT=4. Median number of prior BCG doses = 12. CIS patients have a CR rate of 71% (59/83), with a mediation duration of CR of 24.1 months in responders; 91% avoided cystectomy and 96% 24 month bladder cancer specific progression free survival (defined as progression to MIBC). Papillary patients have a 57% 12 month DFS rate, 48% 24 month DFS rate, and 95% avoided cystectomy. Median time to cystectomy in responders (N=4) is 12.9 months versus 7.8 in non-responders (N=8) for a 5.1 month delay in cystectomy. PK data shows no systemic levels of N-803; thus activity is confined to the bladder. Low grade treatment related AEs (grade 1-2) include dysuria (22%), pollakiurua (19%), hematuria (18%), fatigue (16%), and urgency (12%), all other AEs were seen at 7% or less. No treatment related grade 4 or 5 AE were seen. No treatment emergent SAE's were considered treatment related. No immune related SAE's have been seen. Final data will be presented at AUA. CONCLUSIONS: In 160 patients with BCG-unresponsive NMIBC, there is a 99% bladder cancer specific overall survival at 2 years. In CIS patients 71% CR rate with 24.1 months median duration of response and 96% absence of progression to MIBC at 24 months. 53% DFS rate at 18 months in Papillary disease, N-803+BCG efficacy and safety profile exceeds other available intravesical and systemic options. Source of Funding: ImmunityBio © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1047 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sam Chang More articles by this author Karim Chamie More articles by this author Mark Hidalgo More articles by this author Eugene Kramolowsky More articles by this author Wade Sexton More articles by this author Sandeep Reddy More articles by this author Patrick Soon-Shiong More articles by this author Expand All Advertisement PDF DownloadLoading ...