sBLA for Nogapendekin Alfa Inbakicept in Papillary BCG-Unresponsive NMIBC Is Resubmitted to FDA

The FDA has received a resubmitted supplemental biologics license application (sBLA) seeking approval for nogapendekin alfa inbakicept-pmln (Anktiva) for the treatment of patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with papillary-only tumors.¹

The resubmission follows a January 2026 Type B end-of-phase meeting, in which the FDA requested additional data to support the review of the sBLA after the FDA issued a refusal to file letter for the initial submission in May 2025; the FDA did not ask for the initiation or design of any new clinical trials.^1-3 ImmunityBio, the developer of nogapendekin alfa inbakicept, submitted the requested information in February 2026, and after reviewing the additional data, the FDA provided feedback in March 2026, requesting updated efficacy data.¹ The company then resubmitted the sBLA for patients with papillary-only NMIBC, including long-term follow-up data.

In support of the sBLA, findings from cohort B of the phase 2/3 QUILT-3.032 trial (NCT03022825) revealed that patients with high-grade papillary-only NMIBC who received nogapendekin alfa inbakicept in combination with BCG (n = 80) achieved a 12-month disease-free survival (DFS) rate of 58.2% (95% CI, 46.6%-68.2%), meeting the primary end point of the study.⁴ The 24- and 36-month DFS rates were 52.1% (95% CI, 40.3%-62.7%) and 38.2% (95% CI, 25.6%-50.6%), respectively.

“As far back as 2007, IL-15 was identified by leading scientific and medical organizations, including the NCI [National Cancer Institute], NIH [National Institutes of Health], FDA, AACR [American Association for Cancer Research], and ASH [American Society of Hematology], as the No. 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, stated in a 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, with or without papillary tumors. The long-term data in papillary disease alone demonstrate prolonged DFS and durable bladder preservation, consistent with [nogapendekin alfa inbakicept] IL-15–based mechanism of action.”

What was the design of QUILT-3.032?

QUILT-3.032 was an open-label, multicenter study that enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC.² Other notable inclusion criteria included being at least 18 years of age and having an ECOG performance status of 2 or less. Patients with high-grade Ta and/or T1 disease were required to complete transurethral resection of the bladder tumor of their index lesions before study treatment.

All patients received nogapendekin alfa inbakicept at 400 μg in combination with BCG at 50 mg intravesically weekly for 6 consecutive weeks. The primary end point was DFS at 12 weeks. Secondary end points included progression-free survival (PFS), disease-specific survival (DSS), cystectomy avoidance, and safety.

What were the additional efficacy and safety data from QUILT-3.032?

Further data from cohort B of QUILT-3.032 demonstrated that, at a median follow-up of 30.2 months (range, 3.2-62.8), the median PFS, DSS, and time to cystectomy were all not reached. The respective 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%). The DSS rates at these respective time points were 98.7% (95% CI, 91.4%-99.8%), 96.0% (95% CI, 88.2%-98.7%), and 96.0% (95% CI, 88.2%-98.7%). The respective cystectomy-free rates were 92.2% (95% CI, 83.4%-96.4%), 87.9% (95% CI, 78.0%-93.5%), and 81.8% (95% CI, 68.1%-90.1%).

Patients in the safety population (n = 180) experienced grade 1 or 2 treatment-related adverse effects (TRAEs) at a rate of 61%; grade 3 or higher TRAEs occurred in 3% of patients. No grade 4 or 5 TRAEs, TRAEs leading to death, or immune-related grade 3 TRAEs were reported.

“We welcome FDA Commissioner [Martin A. Makary, MD, MPH’s] recent statements in The New England Journal of Medicine highlighting the importance of a ‘plausible mechanism of action’ as an emerging regulatory pathway,” Soon-Shiong added in the news release.¹ “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.”

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 9, 2026. https://immunitybio.com/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/
2. ImmunityBio advances regulatory discussions with FDA on potential resubmission path for Anktiva in BCG-unresponsive papillary bladder cancer. News release. ImmunityBio, Inc. January 20, 2026. Accessed March 9, 2026. https://immunitybio.com/immunitybio-advances-regulatory-discussions-with-fda-on-potential-resubmission-path-for-anktiva-in-bcg-unresponsive-papillary-bladder-cancer/
3. ImmunityBio requests an urgent meeting with FDA to address the change in the agency’s unambiguous guidance on Jan 2025 to submit an sBLA for NMIBC BCG unresponsive papillary disease, following an inconsistent refusal to file letter on May 2, 2025. News release. ImmunityBio, Inc. May 5, 2025. Accessed March 9, 2026. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-requests-urgent-meeting-fda-address-change-agencys?field_nir_news_date_value[min]=
4. 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-Guérin-unresponsive papillary-only nonmuscle-invasive bladder cancer. J Urol. 2026;215(1):44-56. doi:10.1097/JU.0000000000004782