Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric IL-15 Superagonist, in Healthy Volunteers
Mark P. Rubinstein, Cameron E. Williams, Caroline Mart, Jonathan Beall, Linda MacPherson, Joseph Azar, Marzena Swiderska‐Syn, Paolo Manca, Barry C. Gibney, Mark D. Robinson, Carsten Krieg, Elizabeth G. Hill, Sharif A. Taha, Amy D. Rock, John H Lee, Patrick Soon‐Shiong, John Wrangle
Abstract
Abstract The oncotherapeutic promise of IL-15, a potent immunostimulant, is limited by a short serum t1/2. The fusion protein N-803 is a chimeric IL-15 superagonist that has a >20-fold longer in vivo t1/2 versus IL-15. This phase 1 study characterized the pharmacokinetic (PK) profile and safety of N-803 after s.c. administration to healthy human volunteers. Volunteers received two doses of N-803, and after each dose, PK and safety were assessed for 9 d. The primary endpoint was the N-803 PK profile, the secondary endpoint was safety, and immune cell levels and immunogenicity were measures of interest. Serum N-803 concentrations peaked 4 h after administration and declined with a t1/2 of ∼20 h. N-803 did not cause treatment-emergent serious adverse events (AEs) or grade ≥3 AEs. Injection site reactions, chills, and pyrexia were the most common AEs. Administration of N-803 was well tolerated and accompanied by proliferation of NK cells and CD8+ T cells and sustained increases in the number of NK cells. Our results suggest that N-803 administration can potentiate antitumor immunity.