N-803 Plus BCG Treatment for BCG-Naïve or -Unresponsive Non-Muscle Invasive Bladder Cancer: A Plain Language Review.

This is a summary of two studies that looked at the safety and effectiveness of a potential new treatment, N-803 (Anktiva), in combination with a standard treatment bacillus Calmette-Guerin (BCG) for people with non-muscle invasive bladder cancer (NMIBC).

One study was a Phase 1b study that tested increasing doses of N-803 in combination with the same dose of BCG in people with NMIBC who had never received BCG previously (BCG-naive).

The other study is a Phase 2/3 study of N-803 and BCG in people with NMIBC whose cancer wasn't eliminated by BCG alone (BCGunresponsive).

In the Phase 1b study, the nine participants were split into three groups of 3 participants who received a dose of 100, 200, or 400 μg N-803 along with a standard 50 mg dose of BCG. In the Phase 2/3 study, one group (cohort A) of participants with carcinoma in situ (CIS) disease and another group (cohort B) with papillary disease were treated with 400 μg N-803 plus 50 mg BCG. There was also a cohort C that received only 400 μg N-803. Treatments were delivered directly into the bladder once a week for 6 weeks in a row.

N-803 plus BCG eliminated NMIBC in all nine BCG-naive participants and the effects were long-lasting, with participants remaining NMIBC-free for a range of 8.3 to 9.2 years.As reported in 2022, cancer was eliminated in 58 of 82 (71%) participants with BCG-unresponsive CIS disease and the effect was also long-lasting. Importantly, approximately 90% of the successfully treated participants avoided surgical removal of the bladder. In cohort B participants with papillary disease, 40 of 72 (55.4%) were cancer-free 12 months after treatment. N-803 used alone was only effective in 2 of 10 participants. In both studies, the combination of N-803 and BCG was found to be associated with very few adverse events.Based on results from the Phase 2/3 study, the U.S. Food and Drug Association (FDA) approved the use of N-803 plus BCG for the treatment of BCG-unresponsive bladder CIS with or without Ta/T1 papillary disease.Clinical Trial Registration: NCT02138734 (Phase 1b study), NCT03022825 (Phase 2/3 study).

Addition of the IL-15 superagonist N-803 to BCG therapy produces a high rate of success in eliminating non-muscle invasive bladder cancer in both BCG-naive and BCG-unresponsive patients, with long-lasting effects that allow patients to avoid surgical removal of the bladder.

Future oncology (London, England). 2024 Jul 02 [Epub ahead of print]

Karim Chamie, Sam S Chang, Charles J Rosser, Eugene Kramolowski, Mark L Gonzalgo, Wade J Sexton, Patricia Spilman, Lennie Sender, Sandeep Reddy, Patrick Soon-Shiong

Department of Urology, UCLA Medical Center, Los Angeles, CA, USA., Department of Urology, Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA., Department of Urology, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Virginia Urology, Richmond, VA, USA., Desai Sethi Urology Institute, University of Miami Miller School of Medicine, Miami, FL, USA., Moffitt Cancer Center, Tampa, FL, USA., ImmunityBio, Inc., Culver City, CA, USA.