ImmunityBio has secured approval for Anktiva (N-803, or nogapendekin alfa inbakicept-pmln) in combination with Bacillus Calmette-Guérin (BCG) from the US Food and Drug Administration (FDA) for the treatment of a specific type of bladder cancer.

The approval is for patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) presenting carcinoma in situ (CIS), irrespective of papillary tumours.

Anktiva, which is an IL-15 agonist immunotherapy, obtained breakthrough therapy designation and FDA approval based on its safety and efficacy outcomes, particularly in terms of complete response (CR) rates and duration of complete response (DOR).

In a single-arm, multicentre trial involving 77 assessable patients, the IL-15 agonist was administered alongside BCG maintenance therapy for up to 37 months.

Tumour status was monitored through cystoscopy and urine cytology, with evaluations continuing for up to five years post-trial enrolment for each participant.

The CR rate among the 77 patients stood at 62%, with the upper end of the confidence interval reaching 73%. As of the November 2023 cut-off, the duration of complete response surpassed 47 months and remains ongoing.

The sustained durations of complete response, exceeding 24 months with Anktiva and BCG, surpassed the threshold for clinically significant results set forth by a panel of experts at the International Bladder Cancer Group (IBCG).

Roger Buckley from the IBCG said: “We are pleased that treatment with Anktiva now exceeds the clinically meaningful benchmarks established by the IBCG in 2016 for durable complete response.

“We look forward to the global availability of Anktiva to potentially reduce the need for cystectomy in many patients worldwide with NMIBC.”

Anktiva represents a novel IL-15 superagonist complex comprised of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha. This complex exhibits high affinity binding to IL-15 receptors present on NK, CD4, and CD8 T cells, effectively mimicking the natural biological functions of dendritic cells.

Consequently, it stimulates the generation of memory killer T cells that are selectively primed to target cancer cells. This activation and proliferation of specialised killing cells result in a sustained and robust complete response.

ImmunityBio executive chairman and global chief scientific and medical officer Patrick Soon-Shiong said: “ANKTIVA not only proliferates and activates the patient’s own NK cells and CD8+ killer T cells, but also activates CD4+ T helper cells, thus enhancing the proliferation of memory killer T cells. This novel mechanism of action, which mimics the biology of the dendritic cell, begins the evolution of immunotherapy beyond T cells alone.”

The IL-15 agonist immunotherapy is anticipated to launch in the US around mid-May 2024.

Anktiva has undergone investigation involving over 700 patients across various Phase 1 and 2 trials encompassing both liquid and solid tumours. In addition to ongoing trials focusing on NMIBC, it is currently under evaluation in trials targeting non-small-cell lung cancer, colorectal cancer, non-Hodgkin’s lymphoma, glioblastoma, solid tumours, and HIV.

Future studies are also planned to explore its efficacy in platinum-resistant ovarian cancer and acute myeloid leukemia.