GX-I7(rhIL-7-hyFc, efineptakin alfa), a long-acting IL-7, safely and effectively increased peripheral CD8+ and CD4+ T cells and TILs in patients with solid tumors

Purpose GX-I7 (rhIL-7-hyFc, efineptakin alfa) is a hybrid Fc-fused long-acting recombinant human interleukin-7 (IL-7) developed by Genexine, Inc. with the aim of correcting T-cell deficiency, thereby strengthening the immune response to fight against cancer. This Phase 1b trial ([NCT03478995][1]) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of GX-I7 in patients with locally advanced or metastatic solid tumors. Methods This study consisted of two phases: dose-escalation and expansion. Eight dose groups were administered GX-I7 intramuscularly at doses ranging from 60 to 1700 μg/kg every three or six weeks. Results All regimens were safe and well tolerated, with the most frequently reported adverse drug reactions being injection site reactions, which were manageable with or without pharmacological intervention. GX-I7 demonstrated dose-dependent increases in the maximum serum concentration (Cmax) and area under the curve up to the last measurable concentration (AUClast). In addition, a dose-dependent increase in circulating CD8+/CD4+ T cells was observed. In five patients who consented for biopsy, a statistically significant increase in tumor-infiltrating CD8+/CD4+ T cell lymphocytes after GX-I7 treatment was observed. Conclusion These findings support the use of GX-I7 as a safe and effective T cell-amplifying agent capable of correcting T cell deficiencies. GX-I7 is expected to result in better clinical outcomes when used in combination with other anti-cancer agents by creating a better environment for immune checkpoint inhibitors and anti-cancer treatments to fight cancer. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT03478995 ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: IRBs of Yonsei University Health System Severance Hospital, Seoul Asan Medical Center and Catholic Medical Center gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors All data produced in the present work are contained in the manuscript [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03478995&atom=%2Fmedrxiv%2Fearly%2F2024%2F02%2F14%2F2024.02.12.23299638.atom