Nogapendekin Alfa/BCG BLA Resubmitted For NMIBC Population

The FDA has accepted a resubmission of a supplemental biologics license application (BLA) for nogapendekin alfa inbakicept-pmln (Anktiva) plus Bacillus Calmette-Guérin (BCG) for the treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) harboring papillary tumors, according to a news release from the developer, ImmunityBio.¹

The regulatory decision follows ongoing discussions with the FDA beginning in January 2026, requesting additional data to support its review.² According to the developers, the request did not include the initiation or design of new clinical trials. Requested information was submitted in February 2026. The FDA additionally provided feedback in March, requesting updated efficacy data, with investigators subsequently submitting the supplemental BLA for patients with NMIBC harboring papillary tumors based on long-term follow-up data.

“As far back as 2007, IL-15 was identified by leading scientific and medical organizations, including the NCI, NIH, FDA, AACR, and ASH, as the number 1 ranked immunotherapy molecule with the potential to cure cancer,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, said in the news release.¹ “The mechanism of action of [nogapendekin alfa inbakicept’s] IL-15 superagonist activity was affirmed by the FDA’s approval of [nogapendekin alfa inbakicept] in 2024 for BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors. The long-term data in papillary disease alone demonstrate prolonged disease-free survival and durable bladder preservation, consistent with [nogapendekin alfa inbakicept’s] IL-15-based mechanism of action.”

Findings from cohort B of the phase 2/3 QUILT 3.032 trial (NCT03022825), which included the BCG-unresponsive papillary disease population, supported the acceptance of the supplemental BLA. They were published in The Journal of Urology.² As of the cutoff date of July 15, 2024, the median disease-free survival (DFS) was 25.3 months, with DFS rates of 58.2% (95% CI, 46.6%-68.2%) at 12 months, 52.1% (95% CI, 40.3%-62.7%) at 24 months, and 38.2% (95% CI, 25.6%-50.6%) at 36 months.

Additionally, the median progression-free survival (PFS) among cohort B was not reached (NR; 95% CI, 46.5-NR). The 12-, 24-, and 36-month PFS rates were 94.9% (95% CI, 86.9%-98.0%), 88.7% (95% CI, 78.5%-94.2%), and 83.1% (95% CI, 69.5%-91.0%), respectively.

Patients with BCG-unresponsive NMIBC were enrolled on the trial and assigned to cohorts based on papillary involvement, with cohort B (n = 80) consisting of those with grade Ta/T1 papillary NMIBC and cohort A including those with CIS. Other eligibility criteria included an age of 18 years and older with an ECOG performance status of 0 to 2. Exclusion criteria included inadequate organ function; a history or evidence of muscle-invasive, locally advanced, metastatic, or extravesical bladder cancer within 5 years of study enrollment; and a life expectancy of less than 2 years.

The median age of cohort B was 72 years (range, 46-93), 74% were men, 89% were White, and 76% had a baseline ECOG performance status of 0.

The primary end point for cohort B was DFS rate at 12 months. PFS, disease-specific survival, time to cystectomy, and safety were also assessed.

A total of 61% of patients in cohorts A and B (n = 180) experienced at least 1 grade 1 or 2 treatment-related adverse event (TRAE), with 3% experiencing at least 1 grade 3 or higher event. No grade 4/5 TRAEs, grade 3 immune-related TRAEs, or TRAEs with an outcome of death were reported in cohort B.

The most common TRAEs included dysuria (grade 1, 20%; grade 2, 6%), pollakiuria (16%; 9%), hematuria (18%; 2%), micturition urgency (12%; 4%), and fatigue (14%; 3%). Of note, 2 patients (1%) experienced grade 3 myalgia.

“We welcome FDA commissioner [Martin A. Makary’s, MD, MPH] recent statements in The New England Journal of Medicine highlighting the importance of a ‘plausible mechanism of action’ as an emerging regulatory pathway. The mechanism of action of [nogapendekin alfa inbakicept], which was recognized in the NCI’s 2007 report and reaffirmed in the FDA-approved 2024 package insert, embodies the principles underlying this approach,” Soon-Shiong noted in the release.¹

References

1. ImmunityBio announces resubmission of supplemental BLA to the FDA for ANKTIVA® plus BCG in BCG-unresponsive NMIBC with papillary disease following agency review of additional data. News release. ImmunityBio. March 9, 2026. Accessed March 20, 2026. https://tinyurl.com/3x74wfhf
2. ImmunityBio advances regulatory discussions with FDA on potential resubmission path for ANKTIVA® in BCG-unresponsive papillary bladder cancer. News release. ImmunityBio. January 20, 2026. Accessed March 20, 2026. https://tinyurl.com/y2ujnvxc
3. Chang SS, Chamie K, Kramolowsky E, et al. Prolonged progression-free survival, disease-free survival, and cystectomy avoidance with IL-15 receptor lymphocyte-stimulating agent NAI plus Bacillus Calmette-Guérin in Bacillus Calmette-Guerin-unresponsive papillary-only non muscle-invasive bladder cancer. J Urol. 2026;215(1):44-56. doi:10.1097/JU.0000000000004782