IL-15 Superagonist Anktiva Achieves 57% 12-Month Disease-Free Survival in BCG-Unresponsive Papillary NMIBC in Phase 2/3 Trial

On October 19, 2021, ImmunityBio announced that its IL-15 superagonist complex Anktiva (N-803) in combination with bacillus Calmette-Guérin (BCG) met the primary endpoint for the papillary tumor subgroup in a Phase 2/3 clinical trial for BCG-unresponsive non-muscle-invasive bladder cancer (NMIBC), with 57% of patients achieving a 12-month disease-free survival (DFS) rate. Previously, Anktiva achieved a 72% complete response (CR) rate in patients with the carcinoma in situ (CIS) subgroup.

Bladder cancer is one of the most commonly diagnosed cancers worldwide, with over 570,000 new cases and more than 200,000 deaths reported in 2020. Papillary tumors account for approximately 90% of non-muscle-invasive bladder cancer (NMIBC) cases. Over the past three decades, intravesical Bacillus Calmette-Guérin (BCG) therapy has been the standard of care for patients with non-invasive papillary tumors; however, approximately 40% of patients are non-responsive to this treatment.

The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by influencing the development, maintenance, and function of natural killer (NK) cells and immune T cells. Anktiva consists of an IL-15 mutant (IL-15N72D) complexed with an IL-15 receptor alpha (IL-15Rα)/IgG1 Fc fusion protein. It binds to the IL-15 receptor βγc, directly and specifically stimulating CD8+ T cells and NK cells while avoiding stimulation of regulatory T cells (Tregs). Compared with native, non-complexed IL-15, Anktiva exhibits a superior pharmacokinetic profile in patients, with prolonged persistence in lymphoid tissues and enhanced anti-tumor activity. In December 2019, the U.S. FDA granted Anktiva Breakthrough Therapy Designation.

▲Mechanism of Action of Anktiva (Image source: Reference [2])

At a median follow-up of 17.3 months, Kaplan-Meier analysis showed that the proportion of patients achieving 12-month DFS was 57% (95% CI: 43.7%, 68.5%), and at 18 months it was 53% (95% CI: 38.8%, 64.6%). Durable responses to Anktiva were observed in both the papillary tumor and carcinoma in situ patient cohorts (n=154), with 85% of patients able to avoid cystectomy.

References:

[1] ImmunityBio Announces Primary Endpoint Met in a Second Indication in Bladder Cancer Trial with 57% Disease-Free Survival in Patients with BCG Unresponsive Papillary Disease. Retrieved October 19, 2021, from https://www.businesswire.com/news/home/20211019005500/en

[2] 39th Annual JP Morgan Healthcare Conference. Retrieved February 16, 2021, from https://immunitybio.com/wp-content/uploads/2021/02/2021.01.13-JP-Morgan-Presentation-2021-v6sm-Final-1.pdf

(Original text abridged)

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