Nogapendekin alfa inbakicept (Anktiva), a first-in-class interleukin (IL)–15 agonist, in combination with BCG significantly prolonged duration of complete response (DOCR) compared with BCG alone in patients with BCG-naive non–muscle-invasive bladder cancer (NMIBC), according to interim analysis data from the randomized, registrational phase 1/2 QUILT-2.005 trial (NCT02138734).1
In the interim analysis requested by the FDA, the combination therapy showed a robust maintenance of response. At 6 months, 85% of patients receiving nogapendekin alfa inbakicept plus BCG maintained a CR compared with 57% of patients receiving BCG alone. This trend continued at 9 months, with 84% of patients in the experimental arm maintaining a CR, whereas those receiving BCG alone achieved a rate of 52%. Despite a limited sample size, the difference in duration at 9 months reached statistical significance (P = .0455).
“The interim analysis is encouraging and consistent with findings in the approved BCG-unresponsive setting, where the DOCR has exceeded 47 months,” Patrick Soon-Shiong, MD, founder, executive chairman, and global chief medical and scientific officer of ImmunityBio, stated in a news release.
QUILT-2.005 Trial Interim Analysis: Highlights
- Interim results from the QUILT-2.005 trial demonstrate that combining nogapendekin alfa inbakicept with BCG significantly improved DOCR compared with BCG monotherapy in patients with BCG-naive bladder cancer.
- Nogapendekin alfa inbakicept is an IL-15 agonist that activates NK cells and memory killer T cells to help the immune system overcome tumor resistance.
- With enrollment for the QUILT-2.005 trial more than 85% complete, ImmunityBio, the developer of nogapendekin alfa inbakicept, expects to file a biologics license application to the FDA by the end of 2026.
What is the mechanism of action of nogapendekin alfa inbakicept?
Nogapendekin alfa inbakicept is an IL-15 agonist IgG1 fusion complex that plays a critical role in the immune system by affecting the development and function of natural killer (NK) cells and CD8-positive killer T cells. The agent consists of an IL-15 mutant (IL-15N72D) fused with an IL-15 receptor alpha. By mimicking natural biological properties, it drives the activation and proliferation of NK cells and generates memory killer T cells. This process helps overcome tumor escape phases in clones resistant to T cells, resulting in a prolonged DOCR.
What is the design of the QUILT-2.005 trial?
This ongoing trial is enrolling patients at least 18 years of age with histologically confirmed, high-grade NMIBC of the transitional cell carcinoma subtype.2 Patients need to be currently eligible to receive intravesical BCG therapy, be BCG naive, have an ECOG performance status of 0 to 2, and have adequate pulmonary function.
Patients are being randomly assigned to receive nogapendekin alfa inbakicept at 400 μg plus BCG at 50 mg or BCG alone as induction therapy for 6 consecutive weeks. In the phase 2b portion of the trial, patients are also receiving maintenance therapy with their assigned regimens for 3 consecutive weeks at 3, 6, 12, 18, 24, 30, and 36 months. Patients with eligible disease at 3 months are permitted to receive 6-week re-induction therapy.
