LBA-18 PRELIMINARY PHASE 2 CLINICAL RESULTS OF IL-15RαFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) PATIENTS DEMONSTRATES 82% CR OF CARCINOMA IN SITU (CIS) (2019)

You have accessJournal of UrologySunday Next Frontier (LBA)1 Apr 2019LBA-18 PRELIMINARY PHASE 2 CLINICAL RESULTS OF IL-15RαFC SUPERAGONIST N-803 WITH BCG IN BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER (NMIBC) PATIENTS DEMONSTRATES 82% CR OF CARCINOMA IN SITU (CIS) Karim Chamie, John Lee, Amy Rock, Peter Rhode, Patrick Soon-Shiong, and Sam Chang* Karim ChamieKarim Chamie More articles by this author , John LeeJohn Lee More articles by this author , Amy RockAmy Rock More articles by this author , Peter RhodePeter Rhode More articles by this author , Patrick Soon-ShiongPatrick Soon-Shiong More articles by this author , and Sam Chang*Sam Chang* More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000557510.69076.c9AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: Patients with non-muscle-invasive bladder cancer (NMIBC) who do not respond to Bacillus Calmette-Guérin (BCG) therapy have limited treatment options: the standard of care is radical cystectomy. N-803 (also known as ALT-803) is an IL-15-based immunostimulatory protein complex (IL-15RαFc) that promotes proliferation and activation of natural killer (NK) cells and CD8+ T cells, but not regulatory T cells. Preclinical data have shown that when combined with BCG, N-803 activates cytotoxic lymphocytes and reduces tumor burden. Phase Ib data in BCG-naïve patients with NMIBC demonstrate that intravesical administration of N-803 with BCG induced complete response in all patients, without recurrences for the study duration of 24 months. METHODS: An open-label, single-arm multicenter Phase 2 study of intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC (NCT03022825) was opened. The study has two cohorts: Cohort A, patients with BCG-unresponsive carcinoma in situ (CIS) [with or without Ta or T1 disease] and Cohort B, patients with BCG-unresponsive high-grade Ta/T1 disease. All treated patients receive intravesical N-803 plus BCG, similar to a standard induction and maintenance treatment schedule. The primary endpoint for Cohort A is incidence of complete response (CR) of CIS at any time, and the primary endpoint for Cohort B is disease-free rate at 12 months. RESULTS: To date, forty-six patients have enrolled in this phase 2 trial (Cohort A (CIS), n=23, Cohort B (Papillary), n=23). Of eleven evaluable patients in Cohort A, nine patients (82%) have a reported CR. In addition, seven out of nine (78%) patients in Cohort A demonstrated CR at their 6-month response assessment. Of thirteen evaluable patients in Cohort B, ten patients (77%) showed no evidence of disease at their 3-month response assessment; of these, none (0/8) evaluated beyond 3 months have had disease recurrence. Three serious adverse events (grade 2-3) have been reported (E coli infection, anemia, and bacteremia), with no immune-related AEs. CONCLUSIONS: Nine out of eleven (82%) patients with BCG-unresponsive CIS of the bladder demonstrated a complete response. Ten out of thirteen patients with BCG-unresponsive papillary NMIBC show no evidence of disease at first assessment. Intravesical N-803 plus BCG was well-tolerated and no patients experienced immune-related AEs. Source of Funding: This study was funded by Altor BioScience, a wholly-owned subsidiary of NantCell, Inc. Santa Monica, CA; Culver City, CA; Miramar, FL; Culver City, CA; Nashville, TN© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e999-e1000 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Karim Chamie More articles by this author John Lee More articles by this author Amy Rock More articles by this author Peter Rhode More articles by this author Patrick Soon-Shiong More articles by this author Sam Chang* More articles by this author Expand All Advertisement PDF downloadLoading ...