Stable patient function, health reported with N-803 plus BCG in NMIBC

Patient-reported outcome (PRO) data from the phase 2/3 QUILT 3.032 study (NCT03022825) showed stable 2-year physical function and global health measures with N-803 plus BCG in patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC), according to a news release from ImmunityBio, the developer of N-803.¹

Currently, the FDA is reviewing a resubmission of a biologics license application for N-803 plus BCG.

Patients with both BCG-unresponsive NMIBC carcinoma in situ (CIS) (cohort A) and papillary disease (cohort B) demonstrated stable self-reported physical function and global health over the course of the study. Further, no urinary tract-related symptoms or declines in health were reported among patients from both cohorts who reached 24-month follow-up and completed a bladder cancer questionnaire.

“Many current therapies for bladder cancer slow disease progression but can cause debilitating side effects. The data from the QUILT 3.032 Quality of Life study suggest that many patients not only have a durable response but also report no decline in physical function, which is very important for these patients,” said lead author Karim Chamie, MD, in a news release on the findings.¹ Chamie is an associate professor of urology at the University of California, Los Angeles.

The PRO data is based on a 2-year course of the study, with a data cutoff of May 16, 2022.

Data from the trial also showed that those who achieved a complete response with the combination therapy reported better physical function at 6-month follow-up compared with those who did not achieve a complete response.

The current PRO findings support the previously reported interim results from the QUILT 3.032 study, which showed that 71% of patients in cohort A with CIS with or without Ta/T1 disease achieved a complete response.² The results also showed that the estimated cystectomy avoidance rate for 24 months or longer was 89.2% among responders in cohort A of the study.

Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer at ImmunityBio, added in the news release, “The self-reported stability of health and physical function over the course of the study by the participants reflect another aspect of safety and tolerability of this new combination therapy. Taken together with the positive response rate in cohort A of over 70%, the persistence of responses and cystectomy avoidance, these QoL findings suggest a favorable risk-benefit ratio for this potential new therapeutic option for patients with BCG-unresponsive bladder cancer.”¹

Overall, the phase 2/3 open-label, multicenter, registrational QUILT 3.032 study remains ongoing to assess the safety and efficacy of the investigational interleukin-15 superagonist N-803 in combination with BCG in patients with BCG-unresponsive NMIBC.

The study included 3 cohorts: cohort A, assessing patients with CIS with or without Ta/T1 disease; cohort B, assessing patients with high-grade Ta/T1 papillary disease; and cohort C, assessing N-803 monotherapy in patients with CIS with or without Ta/T1 disease. Cohort C of the study has since been discontinued due to a low response rate with N-803 monotherapy.

The primary end point for patients in cohort A of the study is the incidence of complete responses at 3- and 6-month follow-up. The primary end point for patients in cohort B is the disease-free survival rate at 12 months.

Currently, the FDA is reviewing a resubmission of a biologics license application for N-803 plus BCG for the treatment of patients with BCG-unresponsive NMIBC CIS with or without Ta/T1 disease. A decision on the application is set to be made on or before April 23, 2024.

References

1. ImmunityBio quality-of-life study in BCG-unresponsive bladder cancer trial indicates improved physical function in the 71% complete responders suggesting a favorable risk-benefit ratio for N-803 plus BCG. News release. ImmunityBio, Inc. February 5, 2024. Accessed February 7, 2024. https://www.businesswire.com/news/home/20240205300717/en/

2. Chamie K, Chang SS, Kramolowsky E, et al. IL-15 superagonist NAI in BCG-unresponsive non–muscle-invasive bladder cancer. NEJM Evid. 2023;2(1):EVIDoa2200167. doi:10.1056/EVIDoa2200167