Nogapendekin alfa inbakicept shows high CR, avoidance of cystectomy in NMIBC

Updated data from the phase 2/3 QUILT-3.032 trial (NCT03022825) presented at the 2025 American Urological Association Annual Meeting in Las Vegas, Nevada, demonstrate high complete response (CR) and avoidance of cystectomy rates in patients with high-risk BCG-unresponsive bladder carcinoma in situ (CIS), with or without papillary disease, treated with nogapendekin alfa inbakicept-pmln (NAI; Anktiva).¹

Sam S. Chang, MD, MBA

“This IL-15 superagonist does several things uniquely. First of all, within the bloodstream, you have actually an increased duration or half life. You have an ability to improve binding and then accelerate its ability to bring about an improvement in the immune response. We have proliferation and activation of natural killer cells. We have an impact on the dendritic as well as the T cells themselves, and it’s a combination of increasing this cell kill but not yet stimulating the suppressive T regulatory cells that make this IL-15 superagonist unique,” said QUILT-3.032 principal investigator Sam S. Chang, MD, MBA, professor of urology and Chief Surgical Officer of the Vanderbilt Ingram Cancer Center in Nashville, Tennessee.

Chang also gave an overview of the QUILT-3.032 study, an open-label, single-arm multicenter trial evaluating NAI in patients with BCG-unresponsive NMIBC. The trial included cohort A, which included 100 patients with BCG-unresponsive NMIBC carcinoma in situ (CIS) with or without papillary disease, and cohort B, which included 80 patients with BCG-unresponsive NMIBC papillary disease without CIS. In the induction phase, patients in both cohorts received 400 ug NAI plus 50 mg BCG intravesically for 6 consecutive weeks. There was also a re-induction phase for participants who had not achieved a CR at month 3. The primary end point for cohort A was biopsy-confirmed CR rate that was based on responses at 3- or 6-month assessment. The primary end point for cohort B was disease-free rate assessed at the end of 12 months.

In cohort A, the CR rate 71% (95% CI: 61.1-79.6). The duration of CR in the 71 evaluable responders ranged up to more than 53 months. The cystectomy-free rate at 36 months was 84%. At 36 months, disease-specific overall survival was 99%.

“Exceptional ongoing complete response data were presented for the FDA label population (N=77), which has a longer follow-up time of 29.3 months and showed a 51% probability of duration of complete response of at least 45 months,” ImmunityBio noted in a news release.²

In cohort B, disease-free survival at 12 months was 58% (95% CI: 46.6-68.2) and at 24 months was 52% (95% CI: 40.3-62.7). Median disease-free survival was 25.3 months (95% CI: 9.8-40.1). Chang also reported that in this cohort, treatment with NAI plus BCG yielded cystectomy avoidance rates of 92% at 12 months and 82% at 36 months. The latter figure, according to the presentation, “is the highest percentage of bladder sparing and longest duration available to date in BCG-unresponsive NMIBC papillary disease without CIS.”

Regarding safety, Chang said, “I think importantly, one needs to know that within this trial, there were no grade 4 or grade 5 AEs [adverse events] and overall for grade 3, the treatment-associated side effect [rate] was 3%.”

“Although BCG is the commonly used first-line therapy for newly diagnosed high-risk non-muscle invasive bladder cancer, many patients will be refractory or relapse after an initial response and be diagnosed as BCG-unresponsive. Our latest findings, including an 82% cystectomy avoidance rate, provide additional evidence that ANKTIVA has the ability to restore BCG activity and promote durable complete responses and, most importantly, help patients preserve their bladder for a prolonged duration from surgery in both CIS, as well as papillary without CIS disease,” Chang said in the news release.²

Executive Chairman and Global Chief Medical and Scientific Officer of ImmunityBio Patrick Soon-Shiong, MD, also commented on the data in the news release, saying, “We are pleased with these unmatched long-term follow up results which further illustrate ANKTIVA’s potential to improve outcomes and quality of life for patients with non-muscle invasive bladder cancer in both indications of CIS, as well as papillary disease without CIS. The cystectomy avoidance rate of greater than 82% at 36 months in both BCG-unresponsive CIS with or without papillary disease and in BCG-unresponsive papillary without CIS disease is the highest percentage of bladder sparing and longest duration of complete response and disease-free status seen in this patient population to date, as confirmed by all the studies presented in the field at the AUA 2025 conference. We look forward to the national guidelines (NCCN) for BCG-unresponsive papillary disease without CIS to align with these long-term data of cystectomy avoidance and the data presented at AUA supporting Anktiva as the best in class and best in disease for this indication.”²

ImmunityBio recently announced that it has submitted a supplemental biologics license to the FDA seeking an expanded approval for NAI in combination with BCG for BCG-unresponsive NMIBC in the papillary indication.³

REFERENCE

1. Chang SS, Chamie K, Kramolowsky E, et al. An update on QUILT-3.032: Complete responses to N-803 plus BCG therapy in BCG-unresponsive bladder carcinoma in situ (CIS) with or without Ta/T1 papillary disease. J Urol. 2025;213(5S):e392. doi:10.1097/01.JU.0001109848.08748.9e.12

2. Unmatched long-term bladder preservation for 36 months in over 80 percent of responders with ANKTIVA® plus BCG in BCG-unresponsive NMIBC CIS and papillary disease alone – best in disease and best in class with 5 year follow-up. News release. ImmunityBio. April 28, 2025. Accessed April 28, 2025. https://www.businesswire.com/news/home/20250428844244/en/Unmatched-Long-Term-Bladder-Preservation-for-36-Months-in-over-80-percent-of-Responders-with-ANKTIVA-Plus-BCG-in-BCG-Unresponsive-NMIBC-CIS-and-Papillary-Disease-Alone-Best-in-Disease-and-Best-in-Class-with-5-Year-Follow-Up

3. ImmunityBio announces FDA submissions of supplemental BLA for NMIBC papillary disease and for expanded access of ANKTIVA to treat lymphopenia. News release. ImmunityBio. April 15, 2025. Accessed April 15, 2025. https://immunitybio.com/immunitybio-announces-fda-submissions-of-supplemental-bla-for-nmibc-papillary-disease-and-for-expanded-access-of-anktiva-to-treat-lymphopenia/