FDA Advises on Next Steps for Nogapendekin Alfa Inbakicept Plus BCG sBLA in BCG-Unresponsive Papillary NMIBC

The FDA has completed a Type B End-of-Phase meeting regarding the resubmission of a supplemental biologics license application (sBLA) seeking the approval of nogapendekin alfa inbakicept (Anktiva) in combination with BCG for patients with BCG-unresponsive non–muscle-invasive bladder cancer (NMIBC) with papillary tumors.¹

In May 2025, ImmunityBio—the developer of nogapendekin alfa inbakicept—received a refusal to file (RTF) from the FDA regarding the initial sBLA.2 In the Type B End-of-Phase meeting, the FDA recommended the inclusion of additional information to support resubmission of the sBLA initially; this information has been compiled and will be submitted to the regulatory agency within the next 30 days, according to ImmunityBio.

The sBLA is supported by long-term data from cohort B of the phase 2/3 QUILT-3.032 trial (NCT03022825), which evaluated intravesical nogapendekin alfa inbakicept plus BCG in patients with BCG-unresponsive high-grade, papillary-only NMIBC.¹

The study met its primary end point, with evaluable patients (n = 80) achieving a 12-month disease-free survival (DFS) rate of 58.2% (95% CI, 46.6%-68.2%). With extended follow-up, the disease-specific survival (DSS) rate was 96.0% at 36 months, and the median DSS was not reached. The progression-free survival (PFS) rate was 94.9% at 12 months and 83.1% at 36 months. Bladder preservation signals were also observed, with cystectomy-free survival of 92.2% at 12 months and 81.8% at 36 months.

“The 12- and 36-month survival rates observed with [nogapendekin alfa inbakicept] plus BCG are higher than those reported for other investigational therapies in this patient population,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio, stated in a news release. “Together with the high rate of bladder preservation—with over 80% of patients remaining cystectomy-free at 3 years—these data demonstrate the effectiveness of [nogapendekin alfa inbakicept] in enhancing the immune response against bladder cancer. We remain committed to bringing this important therapy to patients as quickly as possible. Patients with BCG-unresponsive papillary-[only] NMIBC currently have no approved treatment options aside from life-altering radical cystectomy, so our mission is to deliver a safe and effective bladder-sparing treatment to address this urgent unmet need.”

In April 2024, the FDA approved nogapendekin alfa inbakicept plus BCG for the treatment of adult patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors.³ This regulatory decision was also supported by findings from QUILT-3.032.

How was cohort B of the QUILT-3.032 study designed?

QUILT-3.032 was an open-label, multicenter phase 2/3 study that enrolled patients with BCG-unresponsive high-grade Ta/T1 papillary NMIBC.⁴ In cohort B, patients needed to be at least 18 years of age with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC who had an ECOG performance status of 0 to 2. Patients were excluded if they had inadequate organ function, locally advanced, metastatic, and/or extravesical bladder cancer or other tumors within the past 5 years, or a life expectancy of less than 2 years.

Patients received intravesical nogapendekin alfa inbakicept at 400 μg plus 50 mg BCG weekly for 6 consecutive weeks.

The primary end point was DFS rate at 12 months; secondary assessments included PFS, DSS, and cystectomy avoidance. Treatment-related adverse effects (TRAEs) were evaluated to characterize safety.

What was the safety profile of nogapendekin alfa inbakicept plus BCG?

Across Cohorts A and B combined (N = 180), treatment with intravesical nogapendekin alfa inbakicept plus BCG was generally well tolerated, with the majority of TRAEs limited to low-grade, localized urinary symptoms. Overall, 61% of patients experienced at least 1 TRAE of grade 1 or 2 severity, while only 3% experienced a grade 3 or higher TRAE. Importantly, no grade 4 or 5 TRAEs were reported, and there were no treatment-related deaths. In addition, no patients experienced grade 3 immune-related TRAEs.

The most frequently reported TRAEs were consistent with expected local bladder and urinary tract effects associated with intravesical therapy. Dysuria was the most common event, occurring in 27% of patients, with most cases at grade 1 (20%) or grade 2 (6%), and only 1% at grade 3. Other common any-grade urinary effects included pollakiuria (26%), hematuria (21%), micturition urgency (12%), and urinary tract infection (7%), again largely limited to grade 1 or 2 severity. Fatigue was reported in 17% of patients and was exclusively low grade.

Systemic symptoms were infrequent and mild. Chills (7%) and pyrexia (5%) were observed only at grade 1 severity. Bladder spasm (6%) and noninfective cystitis (5%) were uncommon, with isolated grade 3 effects reported in noninfective cystitis (1%). Less frequent TRAEs included nocturia, urinary incontinence, urinary tract pain, myalgia, arthralgia, pain in extremity, and decreased urine flow, each occurring in a small proportion of patients, predominantly at grade 1 severity.

References

1. ImmunityBio advances regulatory discussions with FDA on potential resubmission path for ANKTIVA® in BCG-unresponsive papillary bladder cancer. News Release. ImmunityBio January 20, 2026. Accessed January 22, 2026. https://immunitybio.com/immunitybio-advances-regulatory-discussions-with-fda-on-potential-resubmission-path-for-anktiva-in-bcg-unresponsive-papillary-bladder-cancer/
2. ImmunityBio requests an urgent meeting with FDA to address the change in the agency’s unambiguous guidance on Jan 2025 to submit a sBLA for NMIBC BCG unresponsive papillary disease, following an inconsistent refusal to file letter on May 2, 2025. News release. ImmunityBio. May 5, 2025. Accessed January 22, 2026. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-requests-urgent-meeting-fda-address-change-agencys?field_nir_news_date_value[min]=
3. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed January 22, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
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