High Survival Seen with Nogapendekin Alfa Inbakicept in Papillary NMIBC

Combination therapy with the interleukin-15 (IL-15) superagonist nogapendekin alfa inbakicept (Anktiva) and Bacillus Calmette-Guérin (BCG) elicited a 3-year disease-specific survival (DSS) rate of 96% in patients with BCG-unresponsive, high-grade papillary-only non-muscle invasive bladder cancer (NMIBC), according to new data from the phase 2/3 QUILT-3.032 trial (NCT03022825).^1,2

The findings, published in the January 2026 issue of The Journal of Urology, indicate that the regimen may offer a durable bladder-sparing alternative to radical cystectomy for this patient population.

Study Results and Efficacy

The open-label, multicenter QUILT-3.032 trial evaluated the safety and efficacy of intravesical nogapendekin alfa inbakicept plus BCG. The newly released data focuses on cohort B, which enrolled 80 participants with histologically confirmed BCG-unresponsive high-grade Ta/T1 papillary NMIBC.

At a median follow-up of 36 months, the combination demonstrated a DSS rate of 96.0% (95% CI, 88.2%–98.7%). The median DSS was not reached. The study’s primary end point, disease-free survival (DFS) at 12 months, was 58.2% (95% CI, 46.6%–68.2%). Long-term analysis showed DFS rates of 52.1% at 24 months and 38.2% at 36 months.

Progression-free survival (PFS) remained robust, with 94.9% of patients avoiding progression at 12 months and 83.1% at 36 months. Notably, the trial reported high rates of cystectomy avoidance, a key quality-of-life metric for patients with NMIBC. At 12 months, 92.2% of patients had avoided radical cystectomy; at 36 months, the avoidance rate was 81.8%.

“Patients with BCG-unresponsive papillary-only [NMIBC] have few treatment options, with cystectomy being considered the definitive treatment,” lead author Sam S. Chang, MD, professor of urology and chief surgical officer at Vanderbilt Ingram Cancer Center, said in a news release.² “Our findings provide evidence that [nogapendekin alfa inbakicept] plus BCG would offer a novel and efficacious treatment option for these patients.”

About the Agent

Nogapendekin alfa inbakicept is an IL-15 agonist IgG1 fusion complex. It consists of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha.^1,2 This structure mimics the biological properties of the membrane-bound IL-15 receptor alpha, promoting the activation and proliferation of natural killer (NK) cells and memory CD8+ T cells without inducing the regulatory T-cell expansion often associated with native IL-15. This mechanism is designed to overcome tumor immune evasion and establish long-term immune memory.

Nogapendekin alfa inbakicept is currently approved by the FDA for the treatment of BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors.³

Safety Profile

The safety analysis included 180 patients from both cohort A (carcinoma in situ) and cohort B (papillary-only).^1,2 The adverse event (AE) profile was consistent with that of BCG monotherapy.¹ Treatment-related adverse events (TRAEs) of grade 1 or 2 occurred in 61% of patients. Grade 3 TRAEs were observed in 3% of participants. No grade 4 or 5 TRAEs were reported.

The most common TRAEs (incidence ≥3%) included dysuria, pollakiuria, and hematuria, all of which are expected local reactions to intravesical BCG administration. Systemic immune-related AEs were rare.

REFERENCES

1. 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

2. ANKTIVA® with BCG demonstrates 96% survival from bladder cancer at three years with median survival not yet reached in BCG-unresponsive high-grade papillary-only non–muscle-invasive bladder cancer. News release. ImmunityBio Inc. December 16, 2025. Accessed December 17, 2025. https://tinyurl.com/465yrrvm

3. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. US FDA. April 22, 2024. Accessed December 17, 2025. https://tinyurl.com/3bcnrzwy