FDA Accepts Resubmitted BLA for N-803 Plus BCG in NMIBC
The regulatory agency has set a Prescription Drug User Fee Act date of April 23, 2024 for N-803 plus BCG as a treatment for BCG-unresponsive, non–muscle invasive bladder carcinoma.
Investigators are currently assessing N-803 plus BCG in adult patients with BCG-naïve NMIBC as part of the phase 1b/2b QUILT-2.005 trial (NCT02138734) and in those with BCG-unresponsive NMIBC in the phase 2/3 QUILT-3.032 trial (NCT03022825).
The FDA has accepted a resubmission of a biologics license application (BLA) for N-803 (Anktiva) in combination with Bacillus Calmette-Guérin (BCG) as a treatment for patients with BCG-unresponsive, non-muscle invasive bladder carcinoma (NMIBC) in-situ, according to a press release from ImmunityBio, Inc.1
The FDA previously declined to approve N-803 plus BCGin May 2023.2 The FDA issued a complete response letter after observing deficiencies related to its pre-license inspection of developers’ third-party contract manufacturing organizations.3 The resubmitted BLA constitutes a complete response to the FDA’s previous complete response letter; the agency has set a new Prescription Drug User Fee Act (PDUFA) date of April 23, 2024 for deciding whether to approve N-803 plus BCG in this indication.
“We are pleased that the FDA has accepted ImmunityBio’s resubmission of the BLA as a complete response, following our productive interactions leading up to the resubmission,” Patrick Soon-Shiong, MD, executive chairman and global chief scientific and medical officer at ImmunityBio, said in the press release.1 “We look forward to working closely with the agency to finalize the review and to bringing this important immune-enhancing therapeutic to patients [with] bladder cancer.”
Investigators are currently assessing N-803 plus BCG in adult patients with BCG-naïve NMIBC as part of the phase 1b/2b QUILT-2.005 trial (NCT02138734) and in those with BCG-unresponsive NMIBC in the phase 2/3 QUILT-3.032 trial (NCT03022825).
According to previously published findings in NEJM Evidence, investigators of the QUILT-3.032 trial reported a complete response (CR) rate of 71.0% (95% CI, 59.6%-80.3%) in cohort A, which included patients treated with intravesical N-803 plus BCG.4 Additionally, the median duration of CR in those with a response was 26.6 months (95% CI, 9.9-not reached [NR]).
Across cohort B, which included patients with BCG-unresponsive high-grade Ta or T1 papillary NMIBC, the estimated 12-month disease-free survival (DFS) rate was 55.4% (95% CI, 42.0%-66.8%). Investigators also highlighted a median DFS of 19.3 months (95% CI, 7.4-NR) in this cohort.
The most common treatment-emergent adverse effects reported in the trial included dysuria, pollakiuria, and hematuria, which were expected for intravesical instillation of BCG.
“These data further our understanding of N-803’s unique role in potentially boosting the proliferation of natural killer and T cells while synergistically enhancing BCG efficacy,” Soon-Shiong said in a press release at the time these data were published.5
Patients in the QUILT-3.032 study received 50 mg of intravesical BCG plus 400 μg of intravesical N-803.
The primary end point in cohort A was the incidence of CRs at 3 and 6 months. The primary end point in cohort B was DFS at 12 months.
Patients 18 years and older with histologically confirmed NMIBC of the transitional cell carcinoma high-grade subtype and absence of resectable disease following transurethral resection procedures were able to enroll on the QUILT-3.032 study. Patients also needed to have histologically confirmed presence of BCG-unresponsive carcinoma in-situ and an ECOG performance status of 0 to 2 to enroll.
References
- FDA accepts ImmunityBio’s BLA resubmission as complete and sets new PDUFA date. News release. ImmunityBio, Inc. October 26, 2023. Accessed October 27, 2023. https://shorturl.at/loqMN
- FDA declines to approve ImmunityBio's bladder cancer therapy, shares slump. News release. ImmunityBio. May 11, 2023. Accessed October 27, 2023. bit.ly/3nSoDnj
- US Securities and Exchange Commission. Form 8-K. May 9, 2023. Accessed October 27, 2023. https://shorturl.at/uBR37
- 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). doi:10.1056/EVIDoa2200167
- NEJM Evidence publishes results for ImmunityBio’s QUILT 3.032 registrational trial of IL-15 superagonist N-803 plus BCG in patients with bladder cancer. News release. ImmunityBio, Inc. November 10, 2022. Accessed October 27, 2023. https://shorturl.at/xJM37
