FDA receives resubmitted sBLA for NAI plus BCG in papillary NMIBC

The FDA has acknowledged receipt of a resubmitted supplemental biologics license application (sBLA) for nogapendekin alfa inbakicept-pmln (NAI; Anktiva) plus BCG, seeking to expand its indication to include patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with papillary tumors, ImmunityBio announced in a news release.¹

NAI is a first-in-class IL-15 receptor agonist that stimulates natural killer cells and CD8-positive T cells involved in antitumor immune responses. NAI was approved in April 2024 in combination with BCG for adult patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors.

“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,”² said Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, in the news release.¹ “The mechanism of action of Anktiva’s IL-15 superagonist activity was affirmed by the FDA’s approval of Anktiva in 2024 for BCG-unresponsive NMIBC with 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 Anktiva’s IL-15-based mechanism of action.”

Soon-Shiong added, “We welcome FDA Commissioner Dr [Martin A.] Makary’s recent statements in the New England Journal of Medicine³ highlighting the importance of a ‘plausible mechanism of action’ as an emerging regulatory pathway. The mechanism of action of Anktiva, which was recognized in the NCI’s 2007 report and reaffirmed in the FDA-approved 2024 package insert, embodies the principles underlying this approach.”

The resubmission for NAI plus BCG in the papillary indication follows additional interactions with the FDA in early 2026, during which the agency requested updated efficacy data but did not require initiating new clinical trials. Thus, the resubmitted sBLA is supported by long-term data from cohort B of the phase 2/3 QUILT-3.032 study (NCT03022825), which evaluated intravesical NAI combined with BCG in patients with BCG-unresponsive high-grade papillary-only NMIBC (n = 80).

The results were published in the Journal of Urology, showing that the trial met its primary end point with a 12-month disease-free survival (DFS) rate of 58.2% (95% CI, 46.6-68.2).⁴ At 24 and 36 months, the DFS rates were 52.1% (95% CI, 40.3-62.7) and 38.2% (95% CI, 25.6-50.6), respectively. Disease-specific survival (DSS) reached 98.7% (95% CI, 91.4-99.8) at 12 months and 96.0% (95% CI, 88.2-98.7) at 36 months, with the median DSS not yet reached. Progression-free survival was reported at 94.9% (95% CI, 86.9-98.0) at 12 months and 83.1% (95% CI, 69.5-91) at 36 months.

Bladder preservation outcomes were also reported. Cystectomy-free survival was 92.2% (95% CI, 83.4-96.4) at 12 months and 81.8% (95% CI, 68.1-90.1) at 36 months. The median time to cystectomy had not been reached at the time the data were reported.

Regarding safety, the majority (61%) of treatment-related adverse events (TRAEs) were grade 1 to 2, with 3% being grade 3. No grade 4 or 5 TRAEs were reported.

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. Immunotherapy Agent Workshop. National Cancer Institute; 2007. Accessed March 9, 2026. https://sitc.sitcancer.org/news/nci_manuscript.pdf

3. Prasad V, Makary MA. FDA’s new plausible mechanism pathway. N Engl J Med. 2025;393(23):2365-2367. doi:10.1056/NEJMsb2512695

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