Nogapendekin Alfa Inbakicept Plus BCG Meets Primary End Point in BCG-Naive NMIBC

Nogapendekin alfa inbakicept-pmln (Anktiva; N-803) plus BCG met the primary end point in cohort A of the phase 1b/2b QUILT-2.005 trial (NCT02138734), demonstrating statistically significant efficacy improvement vs BCG alone in BCG-naive non–muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors.¹

ImmunityBio reported that patient-reported quality of life was maintained with the combination, and the most common treatment-emergent and treatment-related adverse effects were consistent with BCG alone, additionally no patients experienced deaths that were treatment-related.

“These results build on the clinical findings observed in patients with BCG-unresponsive NMIBC and underscore the potential of nogapendekin alfa inbakicept plus BCG to become the first chemotherapy-free immunotherapy combination to improve treatment outcomes for patients with BCG-naive bladder cancer,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, stated in the news release. “The statistically significant improvement in efficacy supports our efforts to extend this therapeutic approach to patients earlier in their treatment journey,”

What is the mechanism of action of nogapendekin alfa inbakicept?

Nogapendekin alfa inbakicept is an IL-15 receptor agonist. It comprises an IL-15 mutant complexed with an IL-15 receptor alpha–Fc fusion protein. Receptor binding promotes the proliferation and activation of natural killer cells, CD8-positive T cells.

How was QUILT-2.005 evaluating nogapendekin alfa inbakicept in NMIBC designed?

The open-label, multicenter study comprising an initial phase 1b dose-escalation phase and a randomized phase 2b expansion phase.² The phase 1b portion evaluated safety and established the recommended dose of nogapendekin alfa inbakicept with BCG.

Patients in phase 2b of the trial were randomly assigned to the combination or BCG alone, with stratification by disease and ECOG performance status. The experimental regimen consists of intravesical nogapendekin alfa inbakicept at 400 μg plus BCG at 50 mg once a week for 6 weeks. Maintenance comprises 3 weekly instillations at months 3, 6, 12, 18, 24, 30, and 36. The comparator follows the same BCG schedule. Eligible patients may receive another 6-week induction course.

What end points are being evaluated in QUILT-2.005?

Cohort A’s primary end point is complete response rate at 6 months, assessed using cystoscopy, confirmatory bladder biopsy, and urine cytology. Cohort B’s primary end point is disease-free survival.

Secondary end points include progression-free, overall, and disease-specific survival, as well as duration of complete response, cystectomy-free rate, time to disease worsening, and safety. Quality of life is assessed using the European Organization for Research and Treatment of Cancer questionnaires for patients with cancer and NMIBC-specific QLQ-NMIBC24 questionnaires.

ImmunityBio plans to present additional findings at a medical congress and submit a supplemental biologics license application before year-end 2026.¹

References

1. ImmunityBio announces ANKTIVA plus BCG meets primary endpoint in BCG-naïve non-muscle invasive bladder cancer randomized QUILT-2.005 trial. News release. ImmunityBio. November 9, 2026. Accessed November 9, 2026.
   https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-announces-anktivar-plus-bcg-meets-primary-endpoint
2. A study of intravesical BCG in combination with ALT-803 in patients with non-muscle invasive bladder cancer. ClinicalTrials.gov. Updated March 31, 2026. Accessed November 9, 2026.
   https://clinicaltrials.gov/study/NCT02138734