Immunomodulation profile of the biosimilar trastuzumab MYL-1401O in a bioequivalence phase I study.
Details
Serval ID
serval:BIB_728141A25F81
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Immunomodulation profile of the biosimilar trastuzumab MYL-1401O in a bioequivalence phase I study.
Journal
Scientific reports
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Publication state
Published
Issued date
04/06/2024
Peer-reviewed
Oui
Volume
14
Number
1
Pages
12872
Language
english
Notes
Publication types: Journal Article ; Clinical Trial, Phase I ; Randomized Controlled Trial
Publication Status: epublish
Publication Status: epublish
Abstract
The initial Phase-I single centre, single dose, randomized, double-blind, cross-over study was planned to assess the pharmacokinetic and pharmacodynamic bioequivalence of the trastuzumab biosimilar (MYL-1401O) compared to the reference Herceptin <sup>®</sup> . Their respective immunomodulation profile presented in this paper involved healthy males receiving a single infusion of both monoclonals, separated by a washout period. Sixty parameters were assessed in total, including serum cytokines, peripheral mononuclear cell (PBMC) subsets, cell activation and response to recall antigens and mitogen, pre- and post- infusion, as well as a cytokine release assay (CRA) at baseline. Trastuzumab infusion induced a transient and weak peak of serum IL-6 at 6 h, and a modulation of mononuclear cell subset profile and activation level, notably CD16 + cells. Except for CD8 + T cells, there were no significant differences between Herceptin <sup>®</sup> and MYL-1401O. In CRA, PBMC stimulated with MYL-1401O or Herceptin <sup>®</sup> similarly secreted IL-6, TNF-α, IL-1β, GM-CSF, IFN-γ, and IL-10, but no or low level of IL-2. Interestingly, some observed adverse events correlated with IL-2 and IFN-γ in CRA. MYL-1401O exhibited a very similar immunomodulation profile to Herceptin <sup>®</sup> , strongly supporting its bioequivalence. This approach may thus be included in a proof-of-concept study. CRA may be used as a predictive assay for the evaluation of clinical monoclonals.
Keywords
Humans, Trastuzumab/pharmacokinetics, Biosimilar Pharmaceuticals/pharmacokinetics, Biosimilar Pharmaceuticals/administration & dosage, Male, Therapeutic Equivalency, Adult, Cytokines/metabolism, Cytokines/blood, Cross-Over Studies, Double-Blind Method, Leukocytes, Mononuclear/metabolism, Leukocytes, Mononuclear/drug effects, Leukocytes, Mononuclear/immunology, Immunomodulation/drug effects, Young Adult, Biomarker, Biosimilar, Cytokine release assay, PBMC, Trastuzumab, mAb
Pubmed
Web of science
Open Access
Yes
Create date
14/06/2024 12:04
Last modification date
26/07/2024 7:02