Novel IL-15 superagonist complex highly active in BCG-unresponsive NMIBC

Combining the novel interleukin-15 superagonist complex N-803 (Anktiva) with BCG led to a high complete response rate in patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ.

The combination of N-803 (Anktiva), a novel interleukin-15 (IL-15) superagonist complex, and BCG induced complete responses (CRs) in nearly three-fourths of patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without Ta or T1 disease.1

Results from the first cohort of the phase 2/3 QUILT 3.032 trial showed that 72% (n = 51) of 71 evaluable patients in this population achieved a CR to the combination. The median duration of response was 19.2 months and there was a 59% probability that a CR would be maintained for ≥12 months.

"The high rates of progression and recurrence for NMIBC make it one of the most expensive cancers to treat. This preliminary data is heartening and provides additional evidence of the potential for ImmunityBio’s Anktiva in treating a serious and potentially fatal cancer, for which the alternative is a highly invasive radical cystectomy," Patrick Soon-Shiong, MD, chairman and CEO of ImmunityBio, the developer of N-803, stated in a press release. "We expect to file a Biologics License Application following a meeting with the FDA in 2021."

The investigational superagonist complex N-803 is composed of an IL-15 mutant (IL-15N72D) bound to an IL-15 receptor α/IgG1 Fc fusion protein. In its press release, ImmunityBio maintained that, “N-803 has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced antitumor activity compared to native, non-complexed IL-15 in vivo.”

The open-label, multicenter phase 2/3 QUILT 3.032 trial (NCT03022825) is examining intravesical BCG plus N-803 in patients with BCG-unresponsive high-grade NMIBC. The study includes 3 cohorts. The initial results are from cohort A, which includes patients with BCG-unresponsive CIS with or without Ta or T1 disease. The other cohorts are cohort B, which includes patients with BCG unresponsive high-grade Ta or T1 disease, and cohort C, which includes patients with BCG-unresponsive CIS with or without Ta/T1 papillary disease.

The target enrollment for cohorts A and B is 80 patients each, and the target enrollment for cohort C is 23 patients. Cohort A has completed enrollment. Patients in cohort A and B will receive combination treatment with N-803 plus BCG, while patients in cohort C will receive N-803 alone.

With the initial reported data, the study has met the primary end point of cohort A, which was CR. Regarding safety, there were no treatment-related serious adverse events.

In December 2019, the FDA granted a breakthrough therapy designation to N-803 for use in combination with BCG for the treatment of patients with BCG-unresponsive NMIBC CIS. The designation is intended to expedite the development and review of N-803 in this setting.

N-803 is also being explored in the QUILT 2.005 trial (NCT02138734), which is assessing the superagonist complex in combination with BCG in BCG-naïve patients with high-grade NMIBC.


1. ImmunityBio Announces Primary Endpoint Met of Phase 2/3 Trial for BCG Unresponsive Non-Muscle Invasive Bladder Cancer CIS with 72% Complete Response Rate. Published online December 21, 2020. Accessed December 21, 2020.