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

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

NAI+BCG is already approved for BCG-unresponsive NMIBC with CIS with or without papillary tumors; the sBLA would expand this approval to encompass patients with papillary-only disease, a population for which no FDA-approved therapy currently exists. The Prescription Drug User Fee Act target action date for the FDA review is January 6, 2027.

Supporting Evidence for sBLA: QUILT-3.032 Cohort B Efficacy

The sBLA is supported by 36-month follow-up data from cohort B of the phase 2/3 QUILT-3.032 trial (NCT03022825), a registrational, open-label, single-arm, multicenter study conducted at 32 clinical sites across the United States, published in the Journal of Urology.² The trial enrolled 80 patients with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC who had undergone complete transurethral resection of bladder tumor of their index lesions prior to study entry.

At the July 15, 2024 data cutoff, disease-free survival rates (DFS) were 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, with a median DFS of 25.3 months. The 12-month DFS rate of 58.2% exceeds by at least 14% the 12-month DFS rates reported for other gene and immunotherapies under investigation in this indication, and the median DFS of 25.3 months exceeds the 7.7-month median for pembrolizumab and 12.4-month median for nadofaragene firadenovec in comparable populations.

Progression-free survival (PFS) was 94.9% (95% CI, 86.9%-98.0%) at 12 months, 88.7% (95% CI, 78.5%-94.2%) at 24 months, and 83.1% (95% CI, 69.5%-91.0%) at 36 months, with the median PFS not yet reached. Disease-specific survival rates at 12 and 36 months were 98.7% (95% CI, 91.4%-99.8%) and 96.0% (95% CI, 88.2%-98.7%), respectively, with the median DSS also not reached. Overall survival rates were 98.7% (95% CI, 91.4%-99.8%) at 12 months, 94.7% (95% CI, 86.4%-98.0%) at 24 months, and 91.7% (95% CI, 79.9%-96.7%) at 36 months.

Cystectomy avoidance rates were 92.2% (95% CI, 83.4%-96.4%) at 12 months, 87.9% (95% CI, 78.0%-93.5%) at 24 months, and 81.8% (95% CI, 68.1%-90.1%) at 36 months, with the median time to cystectomy not reached. Notably, the 36-month cystectomy avoidance rate of 81.8% with NAI+BCG exceeded even the 12-month cystectomy avoidance rate of pembrolizumab (76%) and nadofaragene firadenovec (83%) in comparable BCG-unresponsive populations.

Safety Profile for NAI+BCG

The safety of NAI+BCG was assessed across the combined cohorts A and B safety population (N=180). Treatment-related adverse events of grade 1 or 2 occurred in 61% of patients, and grade 3 treatment-emergent adverse events (TRAEs) were reported in only 3% of patients. No grade 4 or grade 5 TRAEs were observed, and there were no immune-related grade 3 TRAEs.²

The most frequently reported TRAEs (occurring in ≥3% of patients) were those expected with intravesical BCG instillation and included dysuria (any-grade, 26%; grade 3, 1%), pollakiuria (any-grade, 25%; grade 3, 1%), hematuria (any-grade, 20%; grade 3, 1%), micturition urgency (any-grade, 16%), fatigue (any-grade, 17%), urinary tract infection (any-grade, 7%; grade 3, 1%), chills (7%), bladder spasm (6%), and pyrexia (5%).

"Patients with BCG-unresponsive NMIBC with papillary disease are faced with the option of a total radical cystectomy and continue to face limited treatment options with no FDA approved therapy to date that strives to preserve the bladder, while reducing the risk of disease progression to muscle-invasive cancer," Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, the developer of NAI, stated in a news release.¹ "The FDA's acceptance of this supplemental application for review represents an important step toward potentially expanding access to ANKTIVA plus BCG for patients with high-grade BCG-unresponsive papillary-only NMIBC and represents an important milestone in our mission to provide patients with bladder-sparing therapeutic options."

QUILT-3.032 Design and Patient Characteristics

QUILT-3.032 (NCT03022825) enrolled patients between July 2017 and July 2024 across 22 US trial sites. Key inclusion criteria included age 18 years or older, ECOG performance status of 0 to 2, and ability to provide informed consent. Patients with a history of muscle-invasive, locally advanced, or metastatic bladder cancer within the prior 5 years, severe cardiac dysfunction, or a life expectancy of fewer than 2 years were excluded. Eligible patients received 400 µg NAI plus 50 mg BCG administered intravesically once weekly for 6 consecutive weeks during induction. The primary end point was DFS at 12 months; secondary end points included PFS, DSS, and cystectomy avoidance, assessed at 12, 24, and 36 months.²

In the 80-patient cohort B efficacy population, the median age was 72 years (range, 46–93). The majority of participants were male (74%) and White (89%). Most patients (76%) had a baseline ECOG performance status of 0. The median number of prior TURBTs was 3 (range, 1–11). In subgroup analyses of PFS at 12 months, high rates were maintained across all evaluated subgroups, including patients with high-grade Ta disease (94.3%), T1 disease (94.6%), high-grade Ta/T1 plus CIS (100%), those with fewer than 12 prior BCG doses (97.4%), those with more than 3 prior TURBTs (94.4%), and those with a history of prior BCG plus other cancer therapy (100%).

Of note, ImmunityBio sponsored an indirect treatment comparison of NAI+BCG vs nadofaragene firadenovec-vncg (Adstiladrin) that was presented at the 2026 AUA Annual Meeting.³ The ITC suggested that there are potential advantages in efficacy with NAI+BCG over nadofaragene firadenovec in patients with BCG-unresponsive NMIBC with carcinoma in situ, with or without papillary disease.

REFERENCES

1. ImmunityBio, Inc. 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. News release. ImmunityBio, Inc; May 20, 2026. Accessed May 20, 2026. https://tinyurl.com/2pxsd5zv

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

3. Jayram G, Ly C, Moradian H, et al. Indirect treatment comparison of nogapendekin alfa inbakicept-pmln plus BCG and nadofaragene firadenovec-vncg in patients with BCG-unresponsive non-muscle invasive bladder cancer CIS ± papillary (NMIBC). J Urol. 2026;215(5 suppl):e711. doi:10.1097/01.JU.0001191716.05440.37.15