| Autor: |
Chamie K; Department of Urology, UCLA Medical Center, Los Angeles., Chang SS; Department of Urology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville., Kramolowsky E; Virginia Urology, Richmond, VA., Gonzalgo ML; Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami., Agarwal PK; Department of Surgery, Section of Urology, University of Chicago, Chicago., Bassett JC; Hoag Urologic Oncology, Hoag Memorial Presbyterian Hospital, Newport Beach, CA., Bjurlin M; Department of Urology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC., Cher ML; Department of Urology, Wayne State University, Detroit.; Karmanos Cancer Center, Detroit., Clark W; Alaska Urological Institute, Soldotna, AK., Cowan BE; Urology Associates, Englewood, CO., David R; Genesis Healthcare Partners, Greater Los Angeles Division, Sherman Oaks, CA., Goldfischer E; Premier Medical Group, Poughkeepsie, NY., Guru K; Roswell Park Comprehensive Cancer Center, Buffalo, NY., Jalkut MW; Associated Urologists of North Carolina, Raleigh, NC., Kaffenberger SD; Department of Urology, University of Michigan, Ann Arbor, MI., Kaminetsky J; University Urology, New York., Katz AE; NYU Winthrop Hospital, Garden City, NY., Koo AS; Genesis Healthcare Partners, Torrance, CA., Sexton WJ; Moffitt Cancer Center, Tampa, FL., Tikhonenkov SN; University of Hawaii Cancer Center, Honolulu., Trabulsi EJ; Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia., Trainer AF; Adult and Pediatric Urology, Omaha, NE., Spilman P; ImmunityBio, Culver City, CA., Huang M; ImmunityBio, Culver City, CA., Bhar P; ImmunityBio, Culver City, CA., Taha SA; ImmunityBio, Culver City, CA., Sender L; ImmunityBio, Culver City, CA., Reddy S; ImmunityBio, Culver City, CA., Soon-Shiong P; ImmunityBio, Culver City, CA. |
| Abstrakt: |
BACKGROUND: Patients with Bacillus Calmette–Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC) have limited treatment options. The immune cell–activating interleukin-15 (IL-15) superagonist Nogapendekin alfa inbakicept (NAI), also known as N-803, may act synergistically with BCG to elicit durable complete responses (CRs) in this patient population. METHODS: In this open-label, multicenter study, patients with BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease were treated with intravesical NAI plus BCG (cohort A) or NAI alone (cohort C). Patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC also received NAI plus BCG (cohort B). The primary end point was the incidence of CR at the 3- or 6-month assessment visit for cohorts A and C, and the disease-free survival (DFS) rate at 12 months for cohort B. Durability, cystectomy avoidance, progression-free survival, disease-specific survival (DSS), and overall survival were secondary end points for cohort A. RESULTS: In cohort A, CR was achieved in 58 (71%) of 82 patients (95% confidence interval [CI]=59.6 to 80.3; median follow-up, 23.9 months), with a median duration of 26.6 months (95% CI=9.9 months to [upper bound not reached]). At 24 months in patients with CR, the Kaplan–Meier estimated probability of avoiding cystectomy and of DSS was 89.2% and 100%, respectively. In cohort B (n=72), the Kaplan–Meier estimated DFS rate was 55.4% (95% CI=42.0% to 66.8%) at 12 months, with median DFS of 19.3 months (95% CI=7.4 months to [upper bound not reached]). Most treatment-emergent adverse events for patients receiving BCG plus NAI were grade 1 to 2 (86%); three grade 3 immune-related treatment-emergent adverse events occurred. CONCLUSIONS: In patients with BCG-unresponsive bladder carcinoma in situ and papillary NMIBC treated with BCG and the novel agent NAI, CRs were achieved with a persistence of effect, cystectomy avoidance, and 100% bladder cancer–specific survival at 24 months. The study is ongoing, with an estimated target enrollment of 200 participants (Funded by ImmunityBio.) |
