2. Academic Validation
  3. IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

IL-15 Superagonist NAI in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer

  • NEJM Evid. 2023 Jan;2(1):EVIDoa2200167. doi: 10.1056/EVIDoa2200167.
Karim Chamie 1,  Sam S Chang 2,  Eugene Kramolowsky 3,  Mark L Gonzalgo 4,  Piyush Kumar Agarwal 5,  Jeffrey C Bassett 6,  Marc Bjurlin 7,  Michael L Cher 8 9,  William Clark 10,  Barrett E Cowan 11,  Richard David 12,  Evan Goldfischer 13,  Khurshid Guru 14,  Mark W Jalkut 15,  Samuel D Kaffenberger 16,  Jed Kaminetsky 17,  Aaron E Katz 18,  Alec S Koo 19,  Wade J Sexton 20,  Sergei N Tikhonenkov 21,  Edouard J Trabulsi 22,  Andrew F Trainer 23,  Patricia Spilman 24,  Megan Huang 24,  Paul Bhar 24,  Sharif A Taha 24,  Lennie Sender 24,  Sandeep Reddy 24,  Patrick Soon-Shiong 24
Affiliations

Affiliations

  • 1 Department of Urology, UCLA Medical Center, Los Angeles.
  • 2 Department of Urology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville.
  • 3 Virginia Urology, Richmond, VA.
  • 4 Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami.
  • 5 Department of Surgery, Section of Urology, University of Chicago, Chicago.
  • 6 Hoag Urologic Oncology, Hoag Memorial Presbyterian Hospital, Newport Beach, CA.
  • 7 Department of Urology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
  • 8 Department of Urology, Wayne State University, Detroit.
  • 9 Karmanos Cancer Center, Detroit.
  • 10 Alaska Urological Institute, Soldotna, AK.
  • 11 Urology Associates, Englewood, CO.
  • 12 Genesis Healthcare Partners, Greater Los Angeles Division, Sherman Oaks, CA.
  • 13 Premier Medical Group, Poughkeepsie, NY.
  • 14 Roswell Park Comprehensive Cancer Center, Buffalo, NY.
  • 15 Associated Urologists of North Carolina, Raleigh, NC.
  • 16 Department of Urology, University of Michigan, Ann Arbor, MI.
  • 17 University Urology, New York.
  • 18 NYU Winthrop Hospital, Garden City, NY.
  • 19 Genesis Healthcare Partners, Torrance, CA.
  • 20 Moffitt Cancer Center, Tampa, FL.
  • 21 University of Hawaii Cancer Center, Honolulu.
  • 22 Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia.
  • 23 Adult and Pediatric Urology, Omaha, NE.
  • 24 ImmunityBio, Culver City, CA.
PMID: 38320011 DOI: 10.1056/EVIDoa2200167
Abstract

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.)

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