NCCN updates bladder cancer guidelines to include NAI plus BCG for papillary NMIBC

The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology for Bladder Cancer to include nogapendekin alfa inbakicept-pmln (NAI; Anktiva) in combination with BCG for patients with BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with papillary-only disease, according to a company announcement.¹

This recommendation expands prior guidance that recognized the combination for patients with carcinoma in situ (CIS) with or without papillary tumors. The addition is classified as a Category 2A recommendation, indicating uniform NCCN consensus based on lower-level evidence.²

Notably, this use in papillary-only disease is not currently included in the FDA-approved indication for NAI, highlighting a current divergence between guideline-supported use and regulatory labeling. ImmunityBio announced resubmission of a supplemental biologics license application to the FDA in early March 2026, seeking approval of the combination of NAI plus BCG in the papillary indication.

“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,” said Patrick Soon-Shiong, MD, founder, executive chairman and global chief scientific and medical officer for ImmunityBio, in the announcement.¹ “The addition of Anktiva plus BCG for papillary-only disease in the NCCN guidelines reflects the growing body of clinical data evaluating Anktiva in this patient population and reinforces our commitment to developing comprehensive treatment solutions that address the full spectrum of patients living with BCG-unresponsive NMIBC.”

The NCCN update is informed in part by findings from the QUILT-3.032 study (NCT03022825), a multicohort clinical trial evaluating NAI plus BCG in patients with BCG-unresponsive NMIBC. In cohort B of the study, which included patients with BCG-unresponsive high-grade papillary only NMIBC (n = 80), the trial met its primary end point with a 12-month disease-free survival (DFS) rate of 58.2% (95% CI, 46.6 to 68.2).³

At 24 and 36 months, the DFS rates were 52.1% (95% CI, 40.3 to 62.7) and 38.2% (95% CI, 25.6 to 50.6), respectively. Disease-specific survival (DSS) was 98.7% (95% CI, 91.4 to 99.8) at 12 months and 96.0% (95% CI, 88.2 to 98.7) at 36 months, with the median DSS not yet reached. Progression-free survival was reported at 94.9% (95% CI, 86.9 to 98.0) at 12 months and 83.1% (95% CI, 69.5 to 91.0) at 36 months.

Bladder preservation outcomes were also reported. Cystectomy-free survival was 92.2% (95% CI, 83.4 to 96.4) at 12 months and 81.8% (95% CI, 68.1 to 90.1) at 36 months. The median time to cystectomy had not been reached at the time of data report.

Regarding safety, the majority (61%) of treatment-related adverse events (TRAEs) were grade 1 to 2, with 3% being grade 3. No grade 4 or 5 TRAEs were reported.

About NAI

Nogapendekin alfa inbakicept is a first-in-class interleukin-15 (IL-15) receptor agonist designed to stimulate natural killer (NK) cells and CD8-positive T cells. By enhancing both innate and adaptive immune responses, the agent aims to overcome tumor immune evasion and promote sustained antitumor activity.

The FDA approved NAI in combination with BCG in April 2024 for adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors. The therapy is administered intravesically with BCG once a week for 6 weeks.

Richard Adcock, president and CEO of ImmunityBio, concluded in the news release, “This update is an important step in the continued evolution of clinical guidance for patients with BCG-unresponsive NMIBC and validates the growing role of immune-based therapies in the treatment landscape.”

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. ImmunityBio. March 17, 2026. Accessed March 18, 2026. https://www.businesswire.com/news/home/20260317965753/en/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

2. Development and Update of Guidelines. National Comprehensive Cancer Network. Accessed March 18, 2026. https://www.nccn.org/guidelines/guidelines-process/development-and-update-of-guidelines

3. Chang SS, Chamie K, Kramolowsky E, et al. Prolonged progression-free survival, disease-free survival, and cystectomy avoidance with IL-15 receptor lymphocyte-stimulating agent NAI plus Bacillus Calmette-Guérin in Bacillus Calmette-Guérin-unresponsive papillary-only nonmuscle-invasive bladder cancer. J Urol. 2026;215(1):44-56. doi:10.1097/JU.0000000000004782