Higher lymphocyte counts predict lower mortality in patients with various oncologic malignancies. Interleukin-7 (IL-7), a homeostatic cytokine, plays a critical and non-redundant role in developing T-cells and maintaining immune functions after development. IL-7 is a potent T-cell amplifier, thereby contributing to immune reconstitution, which may result in clinical benefits. A randomized, double-blind, placebo-controlled, dose-escalation, Phase I study was conducted to assess the safety, tolerability, pharmacokinetic and biological properties of Hyleukin-7 (human IL-7 fused to hyFcTM) administered subcutaneously (SC) and intramuscularly (IM) to healthy volunteers.

Ten subjects randomly received Hyleukin-7 or its matching placebo in an 8:2 ratio in each of three cohorts at 20 and 60 μg/kg SC and 60 μg/kg IM. Dose escalation and switch from SC to IM was determined on 28 days after study drug administration based on the safety and tolerability data. Subjects were followed up to 56 days after dose.

Hyleukin-7 was well tolerated and no subject developed cytokine release syndrome. Injection site reactions were the most common treatment-emergent adverse events, which resolved spontaneously without treatment. Hyleukin-7 was slowly but steadily absorbed and its terminal half-life ranged 48-112 hours. Furthermore, Hyleukin-7 increased absolute lymphocyte counts (ALC) in a dose-dependent manner which lasted during the observed period of 56 days after dose. The mean maximum increase in ALC from baseline was seen 3 weeks after dose. IM Hyleukin-7 increased ALC greater than SC Hyleukin-7 did at the same dose (111.4% IM vs. 75.1% SC). In all of the doses, Hyleukin-7 markedly increased the numbers of all peripheral CD4+ and CD8+ lymphocyte subsets (i.e., naïve, EM, CM and TEMRA). These increases are attributed to enhanced expression of Ki-67.

SC and IM Hyleukin-7 was safe and well-tolerated in a dose range of 20 to 60 μg/kg in healthy subjects. A single SC and IM dose of Hyleukin-7 increased ALC dose-dependently. The results of this study warrant further investigation of Hyleukin-7 as a potential immune-oncology therapeutics to treat patients with compromised T-cell immunity.

Citation Format: Sang Won Lee, Donghoon Choi, MinKyu Heo, Eui-Cheol Shin, Su-Hyung Park, So Jeong Kim, Byung Ha Lee, Se Hwan Yang, Young Chul Sung, Howard Lee. Hyleukin-7, a long-acting interleukin-7, increased absolute lymphocyte counts after subcutaneous and intramuscular administration in healthy subjects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT045.