Final results from a pivotal clinical trial show that the investigational agent N-803 combined with bacillus Calmette-Guérin (BCG) is safe and more effective than other intravesical and systemic options for high-risk nonmuscle-invasive bladder cancer (NMIBC) that is unresponsive to BCG alone, according to an oral presentation at the 2022 ASCO Annual Meeting.

Patients treated with the combination treatment had high rates of complete response (CR), cystectomy avoidance, and cancer-specific survival.

“N-803 combined with BCG has shown to be very safe and effective for patients with BCG-unresponsive bladder cancer,” principal investigator Karim Chamie, MD, associate professor of urology at the University of California, Los Angeles, said in an interview. “The vast majority of the patients enrolled in the clinical trial and received N-803 with BCG had a complete response to the treatment, and more than half of the patients who responded maintained that response for 2 years.”

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N-803 (Anktiva™) is a mutant interleukin-15-based immunostimulatory fusion protein complex that promotes proliferation and activation of natural killer cells and CD8+ T cells, but not regulatory T cells. In a phase 1b trial, administration of intravesical N-803 plus BCG in BCG-naïve patients with NMIBC induced CR without recurrences for the study duration of 24 months, according to investigators.

Dr Chamie presented results from the QUILT-3.032 phase 2/3 trial ( Identifier: NCT03022825), which included 161 patients with BCG-unresponsive high-risk NMIBC divided into 2 cohorts: 84 patients with carcinoma in situ (CIS) and 77 with papillary disease. The overall study population had a median age of 72.3 years, a median number of 12 prior BCG doses, and mean of 4 transurethral resection of bladder tumor procedures.

For initial induction therapy, patients received 50 mg BCG plus 400 µg N-803 intravesically weekly once a week for 6 weeks. The primary endpoint for the CIS group was the incidence of CR. The primary endpoint for the papillary cohort was the disease-free survival (DFS) rate at 12 months.

The CIS group, which had a median follow-up of 23.9 months, had a 71% CR rate with a median 26.6-month duration of CR, Dr Chamie reported. At 24 months, 89% of responders had avoided cystectomy. Bladder cancer-specific survival was 100% at 24 months.

The papillary disease group had a median follow-up of 20.7 months, median 19.3-month DFS, and 12- and 24-month DFS rate of 55% and 48%, respectively. They had a 24-month bladder cancer-specific survival rate of 99%. Cystectomy was avoided in 94% of the patients.

Pharmacokinetic data revealed no systemic levels of N-803, demonstrating that the drug’s activity is confined to the bladder, Dr Chamie reported.

Overall, the investigators observed no treatment-related grade 4 or 5 adverse events (AEs) and no immune-related serious AEs. Low-grade (grade 1-2) treatment-related AEs included dysuria (22% of patients), pollakiuria (20%), hematuria (17%), fatigue (16%), and urgency (12%).

On May 23, ImmunityBio Inc, which is developing N-803, announced that it submitted a Biologics License Application to the US Food and Drug Administration for N-803 for use with BCG as a treatment for BCG-unresponsive NMIBC CIS with or without Ta or T1 disease. If approved, the company said in a press release, N-803 plus BCG would be the first new immunotherapy for this indication in 23 years that can be administered intravesically to induce natural killer cells and T cells.

Disclosure: The study is sponsored by ImmunityBio Inc, for which Dr Chamie has a consulting or advisory role. Several investigators are employed by ImmunityBio. Please see the original reference for a full list of disclosures.


Chamie K, Chang SS, Gonzalgo M, et al. Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). Presented at ASCO 2022; June 3-7, 2022. Abstract 4508.

This article originally appeared on Cancer Therapy Advisor