Nogapendekin Alfa Combo Shows Survival Benefits in BCG-Unresponsive NMIBC

Combining nogapendekin alfa inbakicept-pmln (Anktiva) with Bacillus Calmette-Guérin (BCG) demonstrated long-term efficacy and safety among patients with BCG-unresponsive, papillary-only non-muscle invasive bladder cancer (NMIBC), according to findings from cohort B of the phase 2/3 QUILT-3.032 study (NCT03022825) published in the Journal of Urology.¹

After a median follow-up of 30.2 months (range, 3.2-62.8) for patients without an event, the median progression-free survival (PFS), disease-specific survival (DSS), and time to cystectomy were all not reached (NR). The PFS rates were 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. For DSS, these rates were 98.7% (95% CI, 91.4%-99.8%), 96.0% (95% CI, 88.2%-98.7%), and 96.0% (95% CI, 88.2%-98.7%), respectively. Additionally, the cystectomy-free 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.

The 12-month, 24-month, and 36-month overall survival (OS) rates were 98.7% (95% CI, 91.4%-99.8%), 94.7% (95% CI, 86.4%-98.0%), and 91.7% (95% CI, 79.9%-96.7%), respectively. Data showed disease-free survival (DFS) rates of 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; the median DFS was 25.3 months.

“Patients with BCG-unresponsive papillary-only [NMIBC] have few treatment options, with cystectomy being considered the definitive treatment. Prolongation of [PFS], [DFS] and avoidance of bladder removal are clinically meaningful goals of next-generation chemotherapy-free immunotherapy,” lead study author Sam S. Chang, MD, a professor of Urology and Chief Surgical Officer of the Vanderbilt Ingram Cancer Center, stated in a press release on these data.² “Our findings provide evidence that [nogapendekin alfa] plus BCG would offer a novel and efficacious treatment option for these patients.”

In cohort B of the registrational, open-label, single-arm QUILT-3.032 trial, 80 patients evaluable for efficacy received induction therapy consisting of nogapendekin alfa at 400 μg plus BCG at 50 mg via intravesical administration for 6 consecutive weeks.

The primary end point was DFS at 12 months. Other end points included PFS, DSS, and cystectomy avoidance rates.

Patients 18 years and older with histologically confirmed BCG-unresponsive, high-grade Ta/T1, papillary-only NMIBC were eligible for enrollment on the trial. Those with inadequate organ function or a life expectancy of less than 2 years were ineligible for study entry.

The median patient age was 72 years (range, 46-93), and most were White (89%) and male (74%). Additionally, a majority of the population had an ECOG performance status of 0 (76%), and the median number of prior transurethral resection of the bladder tumor (TURBT) procedures was 3 (range, 1-11).

In a pooled population of 180 patients from cohort B and cohort A—which included those with BCG-unresponsive bladder carcinoma in situ—grade 1/2 treatment-related adverse effects (TRAEs) occurred in 61% of patients, and 3% had grade 3 or higher TRAEs. Of note, investigators reported no grade 4/5 TRAEs, TRAEs leading to death, or immune-related grade 3 TRAEs. The most common grade 1 toxicities included dysuria (20%), hematuria (18%), pollakiuria (16%), fatigue (14%), micturition urgency (12%), and chills (7%).

“The 12- and 36-month rates for [DFS, PFS, and DSS] seen in this study are higher than those reported for other investigational therapies in this patient population. Together with the high rates of cystectomy avoidance, with the median to cystectomy not yet reached, and the 96% bladder cancer-specific survival at 3 years, also with median not yet reached, demonstrates the effectiveness of [nogapendekin alfa] in enhancing the immune response,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer at ImmunityBio, the developer of nogapendekin alfa, concluded in the press release.²

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/mwdvcrjr