Abstract P5-11-09: Sustained efficacy of eflapegrastim in breast cancer patients in a phase 2, open-label, dose-ranging study
Authors: Vacirca JL , Agajanian R , Papai Z , Horvath Z , Makharadze R , Ibrahim EN , Choi MR , Song T , Tedesco KL , McGregor K , Schwartzberg LS 
Published: March 2017

Abstract
Background: Eflapegrastim is a distinct biologic that uses the innovative proprietary long-acting protein/peptide discovery technology (LAPSCOVERY™) and consists of a novel, modified recombinant human G-CSF conjugated to the Fc fragment of IgG4 via a polyethylene glycol linker. A Phase 2 study of 3 doses of eflapegrastim vs pegfilgrastim was conducted in breast cancer patients receiving docetaxel + cyclophosphamide (TC) chemotherapy.
Methods: This was an open-label, global, multicenter, dose-ranging study designed to compare the safety and efficacy of eflapegrastim relative to a fixed dose of pegfilgrastim as a concurrent active control. The study included 4 treatment arms: 3 dose levels of eflapegrastim (45 μg/kg, 135 μg/kg, and 270 μg/kg) vs pegfilgrastim (6 mg). The primary objective of the study was the Duration of Severe Neutropenia (DSN) during Cycle 1. The results for the primary objective, along with demographics and safety, were described in a previous presentation (SABCS 2015 P1-10-05). The secondary endpoints included DSN in Cycles 2-4, absolute neutrophil count (ANC) in Cycles 1-4, the overall incidences of febrile neutropenia (FN) and hospitalization rates.
Results: A total of 147 evaluable patients were enrolled. Patient and tumor characteristics were comparable across all 4 treatment arms. Median age was 59.0 years (range 32 to 77 years); most patients were &lt;65 years (68%), Female (98%), and White (95%). The DSN for the 135 µg/kg and 270 µg/kg was non-inferior to pegfilgrastim during all cycles and the DSN for patients treated with 45 µg/kg was non-inferior during Cycles 2 and 3 (Table 1). The ANC was dose proportional across all 4 cycles. The incidence of FN and hospitalization rates was low in all arms and there were no significant differences between the Eflapegrastim and Pegfilgrastim Arms (Table 2).
Table 1. Duration of Severe Neutropenia in Cycles 2 to 4 of TC Chemotherapy by Treatment ArmDSN (Days)Eflapegrastim 45 μg/kg (N=39)Eflapegrastim 135 μg/kg (N=36)Eflapegrastim 270 μg/kg (N=36)Pegfilgrastim 6 mg (N=36)Cycle 2Difference with pegfilgrastim0.380.04-0.05NANon-Inferiority p-value0.001&lt;0.001&lt;0.001NACycle 3Difference with pegfilgrastim0.310.020.01NANon-Inferiority p-value0.002&lt;0.001&lt;0.001NACycle 4Difference with pegfilgrastim0.940.07-0.02NANon-Inferiority p-value0.781&lt;0.001&lt;0.001NADSN = Duration of Severe Neutropenia; NA = Not Applicable
Table 2. Incidence of Febrile Neutropenia and Hospitalizations Eflapegrastim 45 μg/kg (N=39)Eflapegrastim 135 μg/kg (N=36)Eflapegrastim 270 μg/kg (N=36)Pegfilgrastim 6 mg (N=36)Febrile NeutropeniaIncidence (%)3 (7.7%)1 (2.8%)1 (2.8%)2 (5.6%)Difference with Pegfilgrastim2.1 %-2.8%-2.8%NAp-value1.0001.0001.000NAHospitalizationsIncidence (%)3 (7.7%)3 (8.3%)1 (2.8%)5 (13.9%)Difference with Pegfilgrastim-6.2%-5.6%-11.1%NAp-value0.4690.7100.199NA
Conclusions: In breast cancer patients treated with TC, the non-inferiority of DSN of 135 µg/kg and 270 µg/kg eflapegrastim, compared to pegfilgrastim in Cycle 1, was sustained through Cycles 2-4 and the ANC profiles were comparable in Cycles 1-4. In addition, the overall incidence of FN and hospitalizations was comparable between the eflapegrastim arms and the pegfilgrastim arm.
Citation Format: Vacirca JL, Agajanian R, Papai Z, Horvath Z, Makharadze R, Ibrahim EN, Choi MR, Song T, Tedesco KL, McGregor K, Schwartzberg LS. Sustained efficacy of eflapegrastim in breast cancer patients in a phase 2, open-label, dose-ranging study [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 P5-11-09.