FDA Accepts BLA for N-803 Plus BCG for BCG-Unresponsive Non-Muscle Invasive Bladder Carcinoma in Situ


Patients with Bacillus Calmette-Guérin–unresponsive non-muscle invasive bladder carcinoma in situ appear to benefit from treatment with N-803, leading to the FDA accepting its biologics license application.

A biologics license application (BLA) for N-803 plus Bacillus Calmette-Guérin (BCG) was accepted by the FDA for patients with BCG-unresponsive non-muscle invasive bladder carcinoma (NMIBC) with or without Ta or T1 disease, according to a press release from Immunity Bio.1

The application for the antibody cytokine fusion protein is based on promising findings from the phase 2/3 QUILT 3.032 trial (NCT03022825), which is assessing the combination in the aforementioned patient population. Data from the trial, which were presented at the 2022 Genitourinary Cancers Symposium, indicated that among patients for whom previous therapies have failed, 71% achieved a complete response (CR) with a median duration of response of 26.6 months.2 Moreover, treatment resulted in a cystectomy avoidance rate of 91%, as well as a 24-month bladder cancer overall survival rate of 100%. There were also no serious adverse effects reported.

The prescription drug user fee act date has been set for May 23, 2023.

“This BLA acceptance brings us a very important step closer to being able to offer this promising combination therapeutic to more people living with NMIBC and, ultimately, reduce the incidence of cystectomies,” Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer at ImmunityBio, said in the press release. “This is a compelling example of the power of inducing trained innate immune memory to potentially provide long-term, durable effects against serious, life-threatening diseases.”

N-803, an IL-15 superagonist, has a mechanism of action that results in proliferation of natural killer and T cells, leading to a secondary boost in immunological response from treatment with BCG or other checkpoint inhibitors for other indications.

The study included patients with persistent or recurrent carcinoma in situ within 12 months of undergoing adequate treatment with BCG (cohort A) or papillary recurrent high-grade Ta-T1 disease within 6 months of finishing adequate treatment with BCG. Treatment consisted of 50 mg of BCG plus 400 μg of intravesical N-803 every week for 6 weeks or reinduction for 6 weeks plus maintenance up to a maximum of 3 years.

The trial’s primary end point in cohort A was biopsy-confirmed CR at 3 or 6 months and was disease-free rate at 12 months for cohort B. Secondary end points included duration of CR, cystectomy avoidance, time to cystectomy, and safety.

“We are pleased the FDA has begun its review, and ImmunityBio is prepared to move rapidly to manufacturing and marketing should the Agency approve our therapeutic for this indication,” Richard Adcock, president and chief executive officer at ImmunityBio, concluded.


  1. ImmunityBio Announces FDA Acceptance of Biologics License Application for N-803 in BCG-Unresponsive Non-Muscle-Invasive Bladder Cancer Carcinoma In Situ. News release. Immunity Bio. July 28, 2022. Accessed July 28, 2022. https://bwnews.pr/3oFp7Ki
  2. Chamie K, Chang S, Gonzalgo ML, et al. Phase II/III clinical results of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) carcinoma in situ (CIS) patients. J Clin Oncol. 2021;39(suppl 6):510-510. doi:10.1200/JCO.2021.39.6_suppl.510
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