Phase I Trial Characterizing the Pharmacokinetic Profile of N-803, a Chimeric IL-15 Superagonist, in Healthy Volunteers.
J Immunol
; 208(6): 1362-1370, 2022 03 15.
Article
in En
| MEDLINE
| ID: mdl-35228263
ABSTRACT
The oncotherapeutic promise of IL-15, a potent immunostimulant, is limited by a short serum t 1/2 The fusion protein N-803 is a chimeric IL-15 superagonist that has a >20-fold longer in vivo t 1/2 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 t 1/2 of â¼20 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD8-Positive T-Lymphocytes
/
Interleukin-15
Limits:
Humans
Language:
En
Journal:
J Immunol
Year:
2022
Document type:
Article