IDMC confirms statistical power of pivotal QUILT-2.005 trial in BCG-naïve NMIBC

An independent data monitoring committee (IDMC) has confirmed that enrollment in the pivotal QUILT-2.005 trial is adequate to detect a pre-specified, clinically meaningful difference in complete response (CR) rate between nogapendekin alfa inbakicept-pmln (NAI; Anktiva) plus BCG and BCG monotherapy in patients with BCG-naïve non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without papillary disease, ImmunityBio announced.¹

The committee's recommendation, based on a planned interim analysis of 183 evaluable patients from the fully enrolled study (n = 366), clears the path for a supplemental Biologics License Application (sBLA) submission anticipated in the fourth quarter of 2026.

"Over the past decade, our scientific thesis has been that activating natural killer cells and CD8+ cytotoxic T cells through IL-15 receptor agonism would generate durable immunological memory against bladder cancer. The NCI identified IL-15 as the number one ranked immunostimulatory cytokine nearly two decades ago, and this program has been the clinical validation of that thesis,” explained Patrick Soon-Shiong, MD, Founder, Executive Chairman and Global Chief Medical and Scientific Officer of ImmunityBio, in a news release from the company.¹

QUILT-2.005 (NCT02138734) is a randomized, controlled, open-label, multicenter phase 2b trial that enrolled patients with BCG-naïve NMIBC with CIS, with or without papillary disease (cohort A). Enrollment for cohort A was completed in February 2026, reaching n = 366. Patients are randomly assigned to receive intravesical NAI in combination with BCG or BCG alone. The primary efficacy end point is complete response rate.¹

Per protocol, the planned interim analysis was conducted once 50% of enrolled patients (n = 183) became evaluable for the primary end point. The IDMC reviewed interim CR data comparing NAI plus BCG to BCG alone and concluded that the current enrollment is sufficient to detect the pre-specified clinically meaningful difference at the protocol-specified level of statistical power. No additional enrollment is required.

Earlier interim data from the trial, established from the first 43 patients and presented at the 2024 American Urological Association Annual Meeting, had shown numerically higher rates of durable CR in the combination arm vs BCG alone. Six-month maintained CR rates were 85% vs 57% (P = .0536), and 9-month maintained CR rates were 84% vs 52% (P = .0455). No significant new or worsening safety signals attributable to the addition of NAI to BCG were identified in that analysis.²

Full enrollment data from the now-complete n = 366 cohort will form the basis for final data analysis and the planned sBLA submission.

Soon-Shiong added, “Among participants from the QUILT 2.005 phase 1b study which began in 2014, those patients who enrolled in long-term follow-up (6 of 9 evaluable), all (6 out of 6, 100%) demonstrated a prolonged duration of complete remission with a median survival of 8.8 years with ongoing bladder preservation to date. In addition, the initial interim analysis of QUILT-2.005, performed in the first 43 patients in 2023, further demonstrated a difference in durable complete response when Anktiva is combined with BCG in the BCG-naïve setting. The consistency of durable response from the first 9 patients in 2014, to the next 43 patients in 2023 is encouraging, and I am pleased that statistical power of the randomized trial requires no further enrollment.”

NAI is a first-in-class interleukin-15 (IL-15) receptor agonist designed to stimulate natural killer (NK) cells and CD8-positive T cells involved in antitumor immune responses. NAI was approved in April 2024 in combination with BCG for adult patients with BCG-unresponsive NMIBC with carcinoma in situ (CIS), with or without papillary tumors. A separate sBLA for the BCG-unresponsive papillary-only indication (cohort B of QUILT-3.032) was submitted to the FDA in March 2026.

Richard Adcock, president and CEO of ImmunityBio, concluded, "With Anktiva approved with BCG for adult patients with BCG-unresponsive NMIBC CIS with or without papillary disease in 34 countries and territories, the opportunity to extend its use earlier in the disease course in the BCG-naïve setting represents a substantial expansion of the addressable patient population."

REFERENCES

1. ImmunityBio confirms statistical power in pivotal randomized BCG-naïve NMIBC trial to detect clinically meaningful differences between ANKTIVA® plus BCG versus BCG alone; Supplemental BLA submission on track for 2026. News release. ImmunityBio. March 26, 2026. Accessed March 26, 2026. https://www.businesswire.com/news/home/20260326666809/en/ImmunityBio-Confirms-Statistical-Power-in-Pivotal-Randomized-BCG-Nave-NMIBC-Trial-to-Detect-Clinically-Meaningful-Differences-Between-ANKTIVA-Plus-BCG-Versus-BCG-Alone-Supplemental-BLA-Submission-on-Track-for-2026

2. ANKTIVA synergizes with T cell activity of BCG in both the naïve and unresponsive setting by activating NK cells, interferon gamma, and driving memory CD8+ killer T cells. ImmunityBio. May 2024. Accessed March 26, 2026. https://immunitybio.com/wp-content/uploads/2024/05/ANKTIVA-BCG-Naive.pdf