Nogapendekin Alfa Inbakicept Plus BCG Yields Significant DOR in BCG-Naive NMIBC

Nogapendekin alfa inbakicept (Anktiva), a first-in-class interleukin (IL)–15 agonist, in combination with BCG significantly prolonged duration of complete response (DOCR) compared with BCG alone in patients with BCG-naive non–muscle-invasive bladder cancer (NMIBC), according to interim analysis data from the randomized, registrational phase 1/2 QUILT-2.005 trial (NCT02138734).¹

In the interim analysis requested by the FDA, the combination therapy showed a robust maintenance of response. At 6 months, 85% of patients receiving nogapendekin alfa inbakicept plus BCG maintained a CR compared with 57% of patients receiving BCG alone. This trend continued at 9 months, with 84% of patients in the experimental arm maintaining a CR, whereas those receiving BCG alone achieved a rate of 52%. Despite a limited sample size, the difference in duration at 9 months reached statistical significance (P = .0455).

“The interim analysis is encouraging and consistent with findings in the approved BCG-unresponsive setting, where the DOCR has exceeded 47 months,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio, stated in a news release.

What is the mechanism of action of nogapendekin alfa inbakicept?

Nogapendekin alfa inbakicept is an IL-15 agonist IgG1 fusion complex that plays a critical role in the immune system by affecting the development and function of natural killer (NK) cells and CD8-positive killer T cells. The agent consists of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha. By mimicking natural biological properties, it drives the activation and proliferation of NK cells and generates memory killer T cells. This process helps overcome tumor escape phases in clones resistant to T cells, resulting in a prolonged DOCR.

What is the design of the QUILT-2.005 trial?

This ongoing trial is enrolling patients at least 18 years of age with histologically confirmed, high-grade NMIBC of the transitional cell carcinoma subtype.² Patients need to be currently eligible to receive intravesical BCG therapy, be BCG naive, have an ECOG performance status of 0 to 2, and have adequate pulmonary function.

Patients are being randomly assigned to receive nogapendekin alfa inbakicept at 400 μg plus BCG at 50 mg or BCG alone as induction therapy for 6 consecutive weeks. In the phase 2b portion of the trial, patients are also receiving maintenance therapy with their assigned regimens for 3 consecutive weeks at 3, 6, 12, 18, 24, 30, and 36 months. Patients with eligible disease at 3 months are permitted to receive 6-week re-induction therapy.

CR rate and disease-free survival serve as the primary end points. Key secondary end points include progression-free survival, overall survival, disease-specific survival, time to disease worsening, cystectomy-free rate, safety, and DOCR. Additional end points include immunogenicity and quality of life.

What is the status of the QUILT-2.005 trial?

This study is currently exceeding enrollment expectations, according to the news release.¹ As of the latest update, enrollment of the planned study population is over 85% complete. ImmunityBio anticipates full enrollment will be reached by the second quarter of 2026. Based on current trajectory, the company plans to submit a biologics license application to the FDA by the end of 2026.

How is ImmunityBio addressing the current BCG shortage?

Recognizing the ongoing shortage of TICE BCG, ImmunityBio is progressing with an Expanded Access Program for recombinant BCG to support patient access. The company has requested consultation with the FDA regarding the use of recombinant BCG as an alternative supply source for both clinical needs and patients with BCG-naive disease.

References

1. ImmunityBio advances first-line BCG naive NMIBC program with enrollment exceeding expectations and positive interim analysis for Anktiva plus BCG. News release. ImmunityBio, Inc. January 16, 2026. Accessed January 16, 2026. https://ir.immunitybio.com/news-releases/news-release-details/immunitybio-advances-first-line-bcg-naive-nmibc-program?field_nir_news_date_value[min]=
2. A study of intravesical BCG in combination with ALT-803 in patients with non-muscle invasive bladder cancer. ClinicalTrials.gov. Updated October 16, 2025. Accessed January 16, 2026. https://clinicaltrials.gov/study/NCT02138734