ImmunityBio, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved ANKTIVA (N-803, or nogapendekin alfa inbakicept-pmln) plus Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary tumors. ANKTIVA, a first-in-class IL-15 agonist immunotherapy for NMIBC, received Breakthrough Therapy Designation and approval from the FDA based on the safety and efficacy outcome of complete responses (CR) and duration of complete response (DOR). The 77 evaluable patients in this single-arm, multicenter trial received ANKTIVA with BCG maintenance therapy for up to 37 months.

The tumor status was assessed with cystoscopy and urine cytology and will continue for up to five years after each patient began their participation in the trial. The CR rate for the 77 evaluable patients was 62% with the upper end of the confidence interval being 73%. The duration of complete response as of the November 2023 cut-off was more than 47 months and is ongoing to date.

These prolonged duration of complete response results beyond 24 months with ANKTIVA and BCG exceed the benchmark for the magnitude of meaningful clinical results suggested by a panel of experts at the IBCG. The duration of response is ongoing, so the final median duration of response has yet to be determined. 58% of patients with CR had a DOR = 12 months and 40% had a DOR = 24 months.

ANKTIVA is expected to be available in the U.S. by mid-May 2024. The cytokine interleukin-15 (IL-15) plays a crucial role in the immune system by affecting the development, maintenance, and function of key immune cells?NK and CD8+ killer T cells?that are involved in killing cancer cells. ANKTIVA is a novel IL-15 superagonist complex consisting of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha, which binds with high affinity to IL-15 receptors on NK, CD4, and CD8 T cells.

This mimics the natural biological properties of dendritic cells, and drives the generation of memory killer T cells that have specifically been trained to recognize the cancer cells, resulting in activation and proliferation of these killing cells with durable complete response. ANKTIVA has improved pharmacokinetic properties, longer persistence in lymphoid tissues, and enhanced anti-tumor activity compared to native, non-complexed IL-15 in vivo.