FDA Accepts Supplemental BLA for Nogapendekin Alfa Combo in NMIBC Subtype

The FDA has accepted a supplemental biologics license application (sBLA) for nogapendekin alfa inbakicept-pmln (Anktiva; NAI) in combination with Bacillus Calmette-Guérin (BCG) for the treatment of adult patients with high-grade BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with papillary disease without carcinoma in situ (CIS), according to a news release from the developer, ImmunityBio.¹

The agency accepted the filing to expand treatment options for patients with limited therapeutic selections, setting a Prescription Drug User Fee Act (PDUFA) target action date for January 6, 2027. The submission sought to broaden the combination's current indication by utilizing scientific evidence demonstrating overlapping biological profiles between papillary and CIS disease states.

Efficacy Data

The sBLA was supported by primary efficacy findings showing a 12-month disease-free survival (DFS) rate of 58.2% (95% CI: 46.6%-68.2%) among patients treated with the combination in cohort B of the phase 2/3 QUILT-3.032 trial (NCT03022825).²

Secondary end points demonstrated durable results over long-term follow-up intervals. The progression-free survival (PFS) rate reached 94.9% at 12 months and 82.0% at 36 months, which indicated durable prevention of progression to muscle-invasive disease.

Bladder preservation remained high among patients. The reported cystectomy-free survival rate was 92.2% at 12 months and 83.1% at 36 months. Furthermore, the disease-specific survival (DSS) rate was 96.0% at 36 months. The median DSS had not yet been reached at the time of the sBLA submission.

“The FDA’s acceptance of this supplemental application for review represents an important step toward potentially expanding access to [NAI] plus BCG for patients with high-grade BCG-unresponsive NMIBC,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio, said in the release.¹ ”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.”

Trial Details

QUILT-3.032 was designed as a phase 2/3 clinical trial investigating the chemotherapy-free immunotherapy combination of intravesical NAI plus BCG. The initial FDA approval of the combination in April 2024 for adult patients with BCG-unresponsive NMIBC with CIS, with or without papillary tumors, was based on results from cohort A of the QUILT-3.032 protocol.³

The sBLA for the expanded indication included results from cohort B alongside a literature-based rationale proposing that papillary NMIBC exhibits overlapping clinical and non-clinical profiles with CIS. This scientific data detailing overlapping features were intended to provide adequate justification for the extrapolation of results from cohort A to patients presenting with papillary-only disease.

Patient Characteristics

The regulatory submission was supported by data collected from 80 patients enrolled in cohort B of the trial. All enrolled patients presented with high-grade papillary-only NMIBC. The target population represented individuals with high-risk disease who had become unresponsive to prior BCG therapy and presented with papillary tumors without the presence of CIS.

Main End Points

The primary end point established for cohort B of the QUILT-3.032 trial was the 12-month DFS rate. The secondary end points included PFS, cystectomy-free survival, and DSS.

Safety

The safety data submitted within the supplemental application demonstrated that the safety profile was consistent with the previously approved indication. The serious adverse effects (AEs) associated with NAI when combined with BCG were consistent with the serious AEs observed with BCG alone.

The official prescribing information for the approved indication noted a risk of metastatic bladder cancer with delayed cystectomy, warning that delaying the procedure can lead to lethal muscle-invasive or metastatic disease. The instructions advised that if patients with CIS do not achieve a complete response after a second induction course of NAI with BCG, clinicians should reconsider cystectomy. The approved route of administration for NAI was restricted to intravesical use only, with specific mandates stating it must not be administered via subcutaneous or intravenous routes.

The developers resubmitted a supplemental biologics license applicationfor NAI plus BCG among patients with BCG-unresponsive NMIBC harboring papillary tumors in March 2026.⁴

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. News release. ImmunityBio. May 19, 2026. Accessed May 20, 2026. https://tinyurl.com/yf3bcxf5
2. Jayram G, Ly C, Moradian H, et al. PD25-15: Indirect treatment comparison of nogapendekin alfa inbakicept-pmln plus Bacillus Calmette-Guérin (NAI+BCG) and nadofaragene firadenovec-vncg in patients with BCG-unresponsive non-muscle invasive bladder cancer CIS ± papillary (NMIBC). Presented at: 2026 American Urological Association Annual Meeting; May 15-18, 2026; Washington, DC. Abstract PD25-15
3. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. News release. FDA. April 22, 2024. Accessed April 22, 2024. https://tinyurl.com/husa6m3v
4. 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 May 20, 2026. https://tinyurl.com/3x74wfhf