NCCN Adds Nogapendekin to Bladder Cancer Guidelines

The National Comprehensive Cancer Center Network (NCCN) has added nogapendekin alfa inbakicept-pmln (Anktiva) in combination with Bacillus Calmette-Guérin (BCG) for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with papillary-only disease to its clinical guidelines for bladder cancer, according to a news release from the manufacturer, ImmunityBio, Inc.^1,2

The addition expands previous NCCN clinical guideline recommendations, which included patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary disease, to now also recognize patients with BCG-unresponsive NMIBC with papillary-only disease as candidates for treatment with nogapendekin plus BCG.

The NCCN guideline reference to nogapendekin for patients with BCG-unresponsive NMIBC with papillary-only disease reflects a use that is not included in the current FDA approved indication for the agent.

“These updated NCCN guideline recommendations in bladder cancer represent an important milestone for patients with BCG-unresponsive NMIBC papillary-only disease who have exhausted standard BCG therapy,” Patrick Soon-Shiong, MD, founder, executive chairman and global chief scientific and medical officer of ImmunityBio, said in a release. “We welcome these updated guideline recommendations and await the FDA’s review of ANKTIVA plus BCG for this indication.”

In other regulatory news, the manufacturer has re-submitted a supplemental Biologics License Application for the agent plus BCG in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with papillary tumors following ongoing discussions with the FDA.³

What Is Nogapendekin?

The immunotherapy is designed to activate natural killer (NK) cells and T cells and has demonstrated durable responses in clinical studies.

The cytokine interleukin-15 (IL-15) plays a 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. By activating NK cells, the immunotherapy overcomes the tumor escape phase of clones resistant to T cells and restores memory T cell activity with resultant prolonged duration of complete response.

Nogapendekin is a first-in-class IL-15 agonist IgG1 fusion 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 fusion complex of nogapendekin mimics the natural biological properties of the membrane-bound IL-15 receptor alpha, delivering IL-15 by dendritic cells and driving the activation and proliferation of NK cells with the generation of memory killer T cells that have retained immune memory against these tumor clones.

REFERENCES

1. ImmunityBio Announces NCCN® Clinical Practice Guidelines in Oncology have been updated to include ANKTIVA® plus BCG for patients with BCG-unresponsive NMIBC with papillary-only disease. News release. March 17, 2026. Accessed March 18, 2026. https://tinyurl.com/mw9jkj3y

2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Bladder Cancer. Version 1.2026, March 16, 2026. https://tinyurl.com/2sw4z2zn

3. ImmunityBio Announces Resubmission of Supplemental BLA to the FDA for ANKTIVA® Plus BCG in BCG-Unresponsive NMIBC with Papillary Disease Following Agency Review of Additional Data. News release. March 9, 2026. Accessed March 18, 2026. https://tinyurl.com/et4xusnp