Plenary: Next Frontier, Sunday, Afternoon Session
Presentation Authors: Karim Chamie, Santa Monica, CA, John Lee, Culver City, CA, Amy Rock, Peter Rhode, Miramar, FL, Patrick Soon-Shiong, Culver City, CA, Sam Chang*, Nashville, TN
Introduction: 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.