New more effective BCG immunotherapy for insensitive bladder cancer

Combination therapy with N-803, an experimental immunotherapy, and Bacille Calmette-Guérin (BCG) is safe and effective for the treatment of carcinoma in situ (CIS) and non-muscle invasive papillary bladder cancer (NMIBC) who does not respond to BCG alone, according to new research.

“This combination of BCG and N-803 results in significant complete response rates and long-term disease-free rates without significant systemic side effects,” said researcher Sam S. Chang, MD, of Vanderbilt University Medical Center. in Nashville, Tennessee. in an interview.

“Although direct comparisons [with BCG alone] have not been carried out, these results are very promising,” he added.

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Dr. Chang presented these results, from a Phase 2/3 trial ( Identifier: NCT03022825) at the ASCO Genitourinary Cancers Symposium 2022.

Dr. Chang explained that N-803 is a high-affinity interleukin-15 immunostimulatory fusion protein that promotes the proliferation and activation of natural killer cells and CD8+ T cells without binding to regulatory T cells.

Researchers hypothesized that combining N-803 with BCG would boost innate immune memory and prolong the duration of treatment response.

Dr. Chang and his colleagues tested this theory in 83 patients with IBS and 77 patients with papillary NMIBC. Dr. Chang noted that both groups of patients were heavily pretreated, with a median of 12 prior doses of BCG in each group.

All patients received intravesical N-803 plus BCG. The median follow-up was 23.9 months for the CIS group and 20.7 months for the papillary group.


In the CIS group, the complete response rate was 71%. At 12 and 24 months, 62% and 52% of patients, respectively, had maintained a complete response.

The median duration of response in the CIS group was 24.1 months and 93% of responders avoided cystectomy. At 24 months, the bladder cancer-specific progression-free survival rate was 91% and the overall bladder cancer-specific survival rate was 100%.

The papillary NMIBC group had disease-free survival (DFS) rates at 12 and 24 months of 57% and 48%, respectively. Median SSM was 23.6 months and 95% of patients did not require cystectomy. At 24 months, the overall bladder cancer-specific survival rate was 99%.

In both groups, there were no grade 4 or 5 treatment-related adverse events (TRAE). The incidence of any grade 3 ETRA was less than 1%. There were no serious EITRs and no immune system-related events.

The most common grade 1-2 ETRAs were dysuria (22%), pollakiuria (19%) and haematuria (18%).

Given the observed efficacy and safety profile, N-803 represents a “significant advance” in the treatment of BCG-insensitive CIS and papillary NMIBC, according to the investigators.

Disclosures: This research was supported by ImmunityBio, Inc. Some study authors have disclosed affiliations with biotechnology, pharmaceutical and/or device companies. Please see the original reference for a full list of disclosures.

Read more from Cancer Therapy Advisor coverage of ASCO GU 2022 by visiting the conference page.


Chang SS, Chamie K, Gonzalgo ML, et al. Positive phase 3 efficacy and safety results in CIS and papillary cohorts BCG-insensitive non-muscle invasive bladder cancer (NMIBC) after superagonist IL-15RαFc N-03 (Anktiva) and BCG infusion. Featured at ASCO GU 2022; February 17-19, 2022. Abstract 431.

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