Novel IL-15 Superagonist Study Meets Disease-Free Survival End Point in NMIBC

Bacillus Calmette-Guerin (BCG) in combination with N-803 (Anktiva) helps to extend disease-free survival in patients with BCG-unresponsive high-grade non-muscle invasive bladder cancer (NMIBC), meeting the second primary end point of the phase 2/3 QUILT 3.032 study (NCT03022825), according to a press release by ImmunityBio, Inc.

N-803 is a cytokine interleukin-15 (IL-15) superagonist. The agent is made up of an IL-15 mutant bound to an IL-15 receptor fusion protein. It is meant to directly stimulate CD8-positive T cells and natural killer cells through beta gamma T-cell receptor binding while simultaneously avoiding T-reg stimulation. 

"Intravesical BCG has been the standard of care for more than 30 years for patients with non-invasive papillary tumors, yet unfortunately some 40% of them don’t respond," said Patrick Soon-Shiong, MD, founder and executive chairman and global chief scientific and medical officer of ImmunityBio, in a press release. "Anktiva has demonstrated strong disease control in CIS, and based on the latest data from our study, it is showing the same effect in papillary tumors. This gives us confidence in the potential for all BCG-unresponsive NMIBC patients to benefit from this combination therapeutic."

The QUILT 3.032 study has an estimated enrollment of 180 participants, with an estimated study completion date of January 2023. Primary end points include complete response ate 24 months and the disease-free rate at 12 months. Secondary end points include response at several points between 6 and 24 months.

During the study, all patients received the experimental combination. Cohort A includes patients with carcinoma in situ and cohort B includes patients with papillary disease.

The disease-free survival of cohort B is 57% (95% CI: 43.7%, 68.5%) at 12 months and 53% at 18 months (95% CI: 38.8%, 64.6%). In cohort A, the complete response rate is 72%. Durable responses were seen in both cohorts.

In terms of safety, no serious adverse events (AEs) were reported in Cohort A, and no serious immune-related AEs were reported. Additionally, 85% of patients were able to avoid cystectomy.

In order to participate in the study, patients must be 18 years of age or older, have confirmed NMIBC, be unresponsive to BCG, and an ECOG score of 0-2. Patients with a life expectancy of less than 2 years, abnormal liver function, systematic heart failure, uncontrollable central nervous system metastases, or requiring ongoing chronic steroid therapy, are not eligible to participate.

The study is currently recruiting in Arkansas, California, Florida, Michigan, Nebraska, New Mexico, New York, North Carolina, Pennsylvania, Tennessee, Virginia, and Washington.

_REFERENCES:

_{ImmunityBio announces primary endpoint met in a second indication in bladder cancer trial with 57% disease-free survival in patients with BCG unresponsive papillary disease. ImmunityBio. News release. October 19, 2021. Accessed October 19, 2021. https://bit.ly/3lTLMBP}

_{QUILT-3.032: A multicenter clinical trial of intravesical bacillus calmette-guerin (BCG) in combination with ALT-803 in patients with BCG unresponsive high grade non-muscle invasive bladder cancer. ClinicalTrials.gov. Accessed October 19, 2021. https://bit.ly/3lVGzK7}