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.)
Karim Chamie, M.D.1, Sam S. Chang, M.D.2, Eugene Kramolowsky, M.D.3, Mark L. Gonzalgo, M.D.4, Piyush Kumar Agarwal, M.D.5, Jeffrey C. Bassett, M.D.6, Marc Bjurlin, M.D.7, Michael L. Cher, M.D.8,9, William Clark, M.D.10, Barrett E. Cowan, M.D.11, Richard David, M.D.12, Evan Goldfischer, M.D.13, Khurshid Guru, M.D.14, Mark W. Jalkut, M.D.15, Samuel D. Kaffenberger, M.D.16, Jed Kaminetsky, M.D.17, Aaron E. Katz, M.D.18, Alec S. Koo, M.D.19, Wade J. Sexton, M.D.20, Sergei N. Tikhonenkov, M.D.21, Edouard J. Trabulsi, M.D.22, Andrew F. Trainer, M.D.23, Patricia Spilman, M.A.24, Megan Huang, Ph.D.24, Paul Bhar, M.S.24, Sharif A. Taha, Ph.D.24, Lennie Sender, M.D.24, Sandeep Reddy, M.D.24, and Patrick Soon-Shiong, M.D.24
- Department of Urology, UCLA Medical Center, Los Angeles
- Department of Urology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville
- Virginia Urology, Richmond, VA
- Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami
- Department of Surgery, Section of Urology, University of Chicago, Chicago
- Hoag Urologic Oncology, Hoag Memorial Presbyterian Hospital, Newport Beach, CA
- Department of Urology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC
- Department of Urology, Wayne State University, Detroit
- Karmanos Cancer Center, Detroit
- Alaska Urological Institute, Soldotna, AK
- Urology Associates, Englewood, CO
- Genesis Healthcare Partners, Greater Los Angeles Division, Sherman Oaks, CA
- Premier Medical Group, Poughkeepsie, NY
- Roswell Park Comprehensive Cancer Center, Buffalo, NY
- Associated Urologists of North Carolina, Raleigh, NC
- Department of Urology, University of Michigan, Ann Arbor, MI
- University Urology, New York
- NYU Winthrop Hospital, Garden City, NY
- Genesis Healthcare Partners, Torrance, CA
- Moffitt Cancer Center, Tampa, FL
- University of Hawaii Cancer Center, Honolulu
- Department of Urology, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia
- Adult and Pediatric Urology, Omaha, NE
- ImmunityBio, Culver City, CA