Nogapendekin Alfa Plus BCG Exhibits Efficacy Advantage in NMIBC In Situ

In 2 indirect treatment comparison analyses, nogapendekin alfa inbakicept-pmln (Anktiva; NAI) plus Bacillus Calmette–Guérin (BCG) exhibited favorable efficacy outcomes vs 2 other FDA-approved therapies for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ with or without papillary disease, according to a news release from the developer, ImmunityBio.¹

NAI Plus BCG vs Nadofaragene Firadenovec

According to findings from a podium presentation at the American Urological Association's Annual Meeting (AUA),a matching-adjusted indirect comparison (MAIC) from the phase 2/3 QUILT-3.032 trial (NCT03022825) showed a weighted anytime complete response (CR) rate of 69.7% with NAI plus BCG (cohort A) vs 53.4% for nadofaragene firadenovec-vncg (Adstiladrin) in a phase 3 trial (NCT02773849), for an OR of 2.01 (95% CI, 1.08-3.72).² Additionally, the median duration of response in the respective cohorts was 22.1 months vs 9.7 months, for a median difference of 12.45 months (95% CI, 8.17-17.09). The HR for end of response was 0.57 (95% CI, 0.34-0.95). Moreover, the HR for cystectomy-free survival was 0.40 (95% CI, 0.21-0.75). The overall survival (OS) HR was not statistically different between the 2 arms (95% CI, 0.22-3.31).

"The magnitude and durability of [CR] observed with [NAI plus BCG], combined with a meaningful reduction in the risk of cystectomy, are clinically relevant for patients with BCG-unresponsive NMIBC for whom bladder preservation is the priority," Brooke B. Edwards, MD, chief medical officer at the Urology Group, stated in the news release.¹ "These comparative data, while subject to the inherent limitations of unanchored indirect comparisons, provide context that can support shared decision making with patients considering bladder-sparing therapy."

Additionally, the Kaplan-Meier curves for DOR and cystectomy-free survival consistently showed benefit for the BCG-containing regimen vs nadofaragene firadenovec, and sensitivity analyses using simulated treatment comparison methodology yielded consistent results.

QUILT-3.032 Cohort A vs SunRISe-1 Cohort 2

An additional MAIC made between the cohort A of the QUILT-3.032 protocol and cohort 2 of the phase 2b SunRISe-1 study (NCT04640623), the latter of which evaluated drug-releasing system TAR-200 in a similar BCG-unresponsive NMIBC population, showed an advantage with the NAI plus BCG regimen.³ After matching for variables, the investigators uncovered a similar objective response rate (ORR) between arms, at 49.2% vs 45.9%, respectively (OR, 1.14; 95% CI, 0.61-2.15). Moreover, a 68% reduction in adverse effect (AE) odds was observed between the 2 respective arms, with rates of 61.7% vs 83.5% (OR, 0.32; 95% CI, 0.15-0.67).

Using both MAIC and simulated treatment comparison analyses exhibited consistent safety findings. The E-values exceeded 5 across analyses, with unmeasured confounders potentially negating the findings, requiring a strength of 5 times stronger than the measured baseline risk factors.

“The comparative effectiveness data presented at AUA 2026 reinforce what we have observed across the [nogapendekin alfa inbakicept] development program: that IL-15, working through the trifecta of [natural killer] cells, CD8-positive T cells, and memory T cells, can produce CRs that are not only more frequent but materially more durable than other approved therapies for BCG-unresponsive [NMIBC],” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio, said in the release.¹

Safety

Warnings and precautions for nogapendekin alfa inbakicept include a risk for metastatic bladder cancer with delayed cystectomy, with patients not achieving a CR to treatment after a second induction course of the agent with BCG recommended for cystectomy. Previously reported safety data showed that among patients treated in cohort A of the QUILT-3.032 protocol, most treatment-related AEs (TRAEs) were grades 1 or 2 in severity.⁴

The developers resubmitted a supplemental biologics license applicationfor NAI plus BCG among patients with BCG-unresponsive NMIBC harboring papillary tumors in March 2026.⁵

References

1. ImmunityBio presents favorable comparative effectiveness data in complete response rates of NAI + BCG versus nadofaragene and TAR-200 at AUA 2026. News release. ImmunityBio, Inc. May 19, 2026. Accessed May 19, 2026. https://tinyurl.com/yc7bshpk
2. Jayram G, Ly C, Moradian H, et al. PD25-15: Indirect treatment comparison of nogapendekin alfa inbakicept-pmln plus Bacillus Calmette–Guérin (NAI+BCG) and nadofaragene firadenovec-vncg in patients with BCG-unresponsive non-muscle invasive bladder cancer CIS ± papillary (NMIBC). Presented at: 2026 American Urological Association Annual Meeting; May 15-18, 2026; Washington, DC. Abstract PD25-15
3. Jayram G, Ly C, Moradian H, et al. IP50-12: An indirect treatment comparison (ITC) of nogapendekin alfa inbakicept-pmln plus Bacillus Calmette–Guérin (NAI+BCG) and TAR-200 in patients with BCG-unresponsive, non-muscle invasive bladder cancer CIS±papillary (NMIBC). Presented at: 2026 American Urological Association Annual Meeting; May 15-18, 2026; Washington, DC. Abstract IP50-12
4. 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
5. 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. ImmunityBio. March 9, 2026. Accessed May 19, 2026. https://tinyurl.com/3x74wfhf