Abstract P5-11-08: Immunogenicity of eflapegrastim in a phase 2 open-label dose-ranging study of eflapegrastim in breast cancer patients receiving TC regimen
Authors: Vacirca JL , Papai Z , Agajanian R , Horvath Z , Makharadze R , Ibrahim E , Koli P , Reddy G , Tedesco KL , McGregor K , Schwartzberg LS 
Published: March 2017

Abstract
Background: Eflapegrastim (SPI-2012/HM10460A) is a novel, long-acting recombinant human granulocyte colony-stimulating factor (rhG-CSF). Eflapegrastim consists of an rhG-CSF conjugated to a recombinant E. coli derived Fc fragment of IgG4 via a polyethylene glycol linker. Eflapegrastim is in clinical development for the treatment of chemotherapy induced neutropenia in cancer patients.
Methods: Immunogenicity of eflapegrastim was investigated in an open label, dose-ranging Phase 2 study in breast cancer patients receiving docetaxel + cyclophosphamide (TC) chemotherapy. The study consisted of 4 arms. Patients in Arms 1 through 3 received subcutaneous doses of 45, 135, or 270 µg/kg eflapegrastim and Arm 4 received 6 mg pegfilgrastim (Neulasta®) on Day 2 of each 21-day chemotherapy cycle. Blood samples for immunogenicity analysis were collected before the start of each chemotherapy cycle (Day 1) and at the End-of-Study Visit. Samples were tested in a screening assay for Anti-Drug Antibodies (ADA) to eflapegrastim by a validated enzyme linked immunosorption assay (ELISA). Positive samples from the screening assay were further tested in a confirmatory assay for antibodies binding to eflapegrastim or G-CSF. Samples found positive in the confirmatory assay were further tested in a validated cell based neutralizing antibody assay.
Results: Serum samples from 143 patients in the study were tested for ADA to eflapegrastim and G-CSF. Preexisting antibodies binding to eflapegrastim or G-CSF were detected in 9 out of 143 (6.3%) patients. One out of the 27 patients (3.7%) in the Pegfilgrastim Arm who was negative prior to dosing was positive for ADA in the G-CSF confirmatory assay. Two out of 100 patients (2.0%) treated with eflapegrastim, who were negative prior to dosing, demonstrated treatment-induced formation of ADA in the G-CSF confirmatory assay. However, the responses in these patients were transient (ie, not consistently positive at all the sampling times) and the assay response values were low and only slightly above the plate-specific cut points. None of the patients tested were positive for G-CSF neutralizing antibodies. A formal assessment of the impact of serum ADA on the PK of eflapegrastim was not performed since PK was examined in only a limited number of patients and all of those patients were negative for ADA both at study initiation and post-dose.
Conclusion: No neutralizing antibodies against eflapegrastim or G-CSF were detected in patients administered eflapegrastim in this study.
Citation Format: Vacirca JL, Papai Z, Agajanian R, Horvath Z, Makharadze R, Ibrahim E, Koli P, Reddy G, Tedesco KL, McGregor K, Schwartzberg LS. Immunogenicity of eflapegrastim in a phase 2 open-label dose-ranging study of eflapegrastim in breast cancer patients receiving TC regimen [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-08.