FDA Accepts sBLA for Nogapendekin Alfa Inbakicept in Papillary-Only BCG-Unresponsive NMIBC

The FDA has accepted for review a supplemental biologics license application (sBLA) seeking the approval of nogapendekin alfa inbakicept-pmln (Anktiva) in combination with BCG for the treatment of adult patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with papillary disease without carcinoma in situ (CIS).¹

The agency has set a goal date of January 6, 2027, for the sBLA under the Prescription Drug User Fee Act. If approved, the expanded indication would represent the first FDA-approved bladder-sparing therapy specifically for patients with BCG-unresponsive NMIBC with papillary-only disease.

The sBLA is supported in part by data from Cohort B of the phase 2/3 QUILT-3.032 trial (NCT03022825). Findings published in The Journal of Urology showed a 12-month disease-free survival (DFS) rate of 58.2% (95% CI, 46.6%-68.2%) among patients with high-grade papillary-only NMIBC who received the regimen (n = 80).²

The 12- and 36-month progression-free survival (PFS) rates were 94.9% (95% CI, 86.9%-98.0%) and 83.1% (95% CI, 69.5%-91.0%), respectively; the corresponding cystectomy-free survival (CFS) rates were 92.2% (95% CI, 83.4%-96.4%) and 81.8% (95% CI, 68.1%-90.1%), respectively. The disease-specific survival rate (DSS) was 96.0% at 36 months (95% CI, 88.2%-98.7%), with the median DSS not yet reached (NR; 95% CI, NR-NR) at the time of sBLA submission.^1,2

In the filing communication, the FDA stated¹, “In support of this expansion, you have submitted the results of QUILT-3.032 Cohort B and a literature-based rationale proposing that papillary NMIBC has an overlapping clinical and non-clinical profile with CIS that may allow for extrapolation of results from patients with CIS, as was demonstrated in QUILT-3.032 Cohort A, the basis of the existing indication, to those with papillary-only disease.”

Of note, the FDA stated that the scientific data detailing the overlapping features between CIS and papillary histology will be the focus of the review to determine whether extrapolation from Cohort A to Cohort B is adequately justified. The agency also reiterated their concerns regarding single-arm trials in papillary disease alone (Cohort B), as the initial indication for CIS and papillary disease (Cohort A) was already based upon a single-arm trial.

“The FDA’s acceptance of this supplemental application for review represents an important step toward potentially expanding access to [nogapendekin alfa inbakicept] plus BCG for patients with high-grade BCG-unresponsive NMIBC,” Patrick Soon-Shiong, MD, founder, executive chairman and global chief scientific and medical officer of ImmunityBio, stated in a news release. “We were encouraged by the scientific discussion at the recent FDA workshop regarding the biological overlap between CIS and papillary disease and the current real-world treatment approaches for these patients. We look forward to continuing to work with the agency during its review of the application.”

Additional data from QUILT-3.032, including longer follow-up on DSS, PFS, and cystectomy-free survival in Cohort B, have been submitted to the FDA as part of the sBLA package.

How was the QUILT-3.032 trial designed?

QUILT-3.032 was a registrational, open-label, single-arm, multicenter trial evaluating intravesical nogapendekin alfa inbakicept plus BCG in patients with high-grade BCG-unresponsive NMIBC.² The study comprised 3 cohorts. Cohort B, which forms the basis of the current sBLA, enrolled 80 patients 18 years of age or older with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC who had an ECOG performance status of 1 to 2 and a complete TURBT of their index lesion(s) before study treatment. Those with a history or evidence of muscle-invasive, locally advanced, metastatic, and/or extravesical bladder or other cancer within the past 5 years were excluded from the study.

Eligible patients received intravesical nogapendekin alfa inbakicept in combination with BCG. The primary end point was 12-month DFS rate. Secondary end points included PFS, CFS, and DSS.^1,2

What was the safety profile of nogapendekin alfa inbakicept plus BCG in QUILT-3.032?

The safety profile of the regimen was tolerable and consistent with BCG alone. The most common treatment-related adverse effects (TRAEs; incidence ≥3%) for patients who received the combination in both cohorts A and B (n = 180) were related to bladder instillation, including dysuria, pollakiuria, and hematuria. The overall incidence of grade 1/2 TRAEs was 61%; 3% of TRAEs were grade 3, and grade 4 or 5 TRAEs were reported. All individual grade 3 TRAEs occurred at an incidence of 1%, including dysuria, pollakiuria, and hematuria.

What are the current indications for nogapendekin alfa inbakicept plus BCG?

In April 2024, nogapendekin alfa inbakicept plus BCG received FDA approval for adult patients with BCG-unresponsive NMIBC with CIS, with or without papillary tumors, based on data from Cohort A of the QUILT-3.032 trial.¹ Of note, this approval made nogapendekin alfa inbakicept the first IL-15 receptor agonist approved by the FDA. The current sBLA seeks to expand that indication to patients with papillary-only disease.

Additionally, in March 2026, the National Comprehensive Cancer Network (NCCN) designated intravesical nogapendekin alfa inbakicept plus BCG for BCG-unresponsive NMIBC with papillary-only disease as a Category 2A recommendation, reflecting uniform NCCN consensus based on lower-level evidence that the intervention is appropriate.

References

1. ImmunityBio announces FDA acceptance of supplemental BLA for ANKTIVA plus BCG in BCG-unresponsive non-muscle invasive bladder cancer with papillary disease; PDUFA date set for January 6, 2027. ImmunityBio. May 19, 2026. Accessed May 20, 2026. https://immunitybio.com/immunitybio-announces-fda-acceptance-of-supplemental-bla-for-anktiva-plus-bcg-in-bcg-unresponsive-non-muscle-invasive-bladder-cancer-with-papillary-disease-pdufa-date-set-for-january-6-2027/
2. 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