Nogapendekin Alfa Inbakicept Is Under EMA Review for BCG-Unresponsive NMIBC With CIS

The European Medicines Agency (EMA) has accepted for review a marketing authorization application (MAA) seeking the approval of 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 carcinoma in situ (CIS) with or without papillary tumors.1

This MAA was supported by findings from the ongoing phase 2/3 QUILT-3.032 trial (NCT0302285), in which, as of a data cutoff of July 15, 2024, the complete response (CR) rate with nogapendekin alfa inbakicept plus BCG among the 100 evaluable patients with BCG-unresponsive high-grade NMIBC with CIS (cohort A) was 71%.1,2 In patients with a CR, the duration of response (DOR) ranged from 0.03 months to 54 months and ongoing.1

“We are encouraged by the speed in which the EMA accepted our MAA and determined it would begin its assessment of our innovative treatment for this serious condition, just 9 months after [the agent] was first approved by the FDA for use in the United States,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief scientific and medical officer of ImmunityBio, stated in a news release. “Along with our submission to the United Kingdom’s Medicines and Healthcare products Regulatory Agency, this action by the EMA is strong evidence of the momentum for putting [nogapendekin alfa inbakicept] plus BCG into the hands of physicians who are treating patients with NMIBC.”

Nogapendekin alfa inbakicept is a first-in-class interleukin-15 (IL-15) agonist IgG1 fusion complex that binds with high affinity to IL-15 receptors on natural killer, CD4-positive, and CD8-positive T cells.

In April 2024, the FDA approved nogapendekin alfa inbakicept plus BCG for the treatment of adult patients with BCG-unresponsive NMIBC with CIS with or without papillary tumors.3 This regulatory decision was supported by data from 77 evaluable adult patients with BCG-unresponsive, high-risk NMIBC with CIS with or without Ta/T1 papillary disease following transurethral resection who were included in the single-arm, multicenter QUILT-3.032 trial.

In the trial, patients received 400 mcg of nogapendekin alfa inbakicept induction therapy via intravesical instillation with BCG for 6 consecutive weeks during the induction period.4 Then, patients with no or low-grade disease received maintenance treatment once weekly every 3 weeks at 4, 7, 10, 13, and 19 months, whereas patients with persistent CIS or high-grade Ta disease at 3 months were eligible to receive a second induction course. Patients with ongoing CR at 25 months were permitted to receive additional instillations once weekly every 3 weeks at months 25, 31, and 37.

In this report, patients had a median age of 73 years (range, 50-91), 86% were male, 90% were White, and 83% had an ECOG performance status of 0. At baseline, 57% of patients had relapsed NMIBC, and 43% had refractory disease. Patients had received a median of 12 prior doses of BCG (range, 8-45).

The CR rate was 62% (95% CI, 51%-73%), and the DOR ranged from 0.0 months to longer than 47.0 months. Furthermore, 58% of patients who achieved a CR had a DOR of at least 12 months, and 40% of patients who achieved a CR had a DOR of at least 24 months.

The most common adverse effects observed in at least 15% of safety-evaluable patients included increased creatinine levels (any-grade, 76%; grade 3/4, 0%), dysuria (32%; 0%), hematuria (32%; 3.4%), urinary frequency (27%; 0%), micturition urgency (25%; 0%), urinary tract infection (24%; 2.3%), increased potassium levels (18%; 2%), musculoskeletal pain (17%; 2.3%), chills (15%; 0%), and pyrexia (15%; 0%).

References

1. ImmunityBio announces European Medicines Agency acceptance of marketing authorization application for Anktiva for the treatment of patients with BCG-unresponsive non-muscle invasive bladder cancer carcinoma in situ. News release. ImmunityBio. January 27, 2025. Accessed January 27, 2025. https://www.businesswire.com/news/home/20250127517387/en
2. Chamie K, Chang SS, Gonzalgo M, et al. Final clinical results of pivotal trial of IL-15RαFc superagonist N-803 with BCG in BCG-unresponsive CIS and papillary nonmuscle-invasive bladder cancer (NMIBC). J Clin Oncol. 2022:40(suppl 16):4508. doi:10.1200/JCO.2022.40.16_suppl.4508
3. FDA approves nogapendekin alfa inbakicept-pmln for BCG-unresponsive non-muscle invasive bladder cancer. FDA. April 22, 2024. Accessed January 27, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nogapendekin-alfa-inbakicept-pmln-bcg-unresponsive-non-muscle-invasive-bladder-cancer
4. Anktiva. Prescribing information. Altor BioScience. April 2024. Accessed January 27, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/761336s000lbl.pdf