title: Immunogenicity Assessment of Lipegfilgrastim in Patients with Breast Cancer Receiving Chemotherapy.
abstract: Lipegfilgrastim is a long-acting, once-per-cycle, glycopegylated recombinant granulocyte colony-stimulating factor (G-CSF) used to prevent neutropenia in patients receiving myelosuppressive chemotherapy. This integrated analysis examined the immunogenicity of lipegfilgrastim and its potential clinical impact in two double-blind randomized studies (phases II and III) of patients with breast cancer receiving chemotherapy. Serum samples were analyzed using sequential assays for screening, confirmation, antibody titer, and characterization of antidrug antibodies (ADA). Neutropenia-related efficacy measures were reviewed for each ADA-positive patient. Among 255 patients receiving lipegfilgrastim (154 in phase II, 101 in phase III) and 155 patients receiving pegfilgrastim (54 in phase II, 101 in phase III), the incidence of treatment-emergent ADA was low and similar between the lipegfilgrastim (phase II: 1.3%; phase III: 1.0%) and pegfilgrastim (phase II: 1.9%; phase III: 1.0%) arms. None of the treatment-emergent ADA-positive samples exhibited neutralizing activity against lipegfilgrastim, pegfilgrastim, or glycosylated G-CSF in a cell-based neutralizing antibody assay. No changes were observed in neutropenia-related efficacy measures among ADA-positive patients, and no treatment-related hypersensitivity or anaphylaxis occurred. These results indicate that there is no apparent impact of ADA on lipegfilgrastim efficacy and safety.
authors.affiliation: Global Bioassays and Technology, Teva Pharmaceuticals, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA.
authors.forename: Linglong
authors.identifier: 0000-0002-0904-4662
authors.initials: L
authors.lastname: Zou
authors.affiliation: Merckle GmbH, Graf-Arco-Straße 3, 89079 Ulm, Germany.
authors.forename: Anton
authors.initials: A
authors.lastname: Buchner
authors.affiliation: CIRION BioPharma Research Inc., 3150 rue Delaunay, Laval, QC, Canada H7L 5E1.
authors.forename: Martin
authors.initials: M
authors.lastname: Roberge
authors.affiliation: Global Bioassays and Technology, Teva Pharmaceuticals, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA.
authors.forename: Patrick M
authors.identifier: 0000-0002-7467-7386
authors.initials: PM
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D007518:Isoantibodies; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D000069585:Filgrastim