GX-G3, a long-acting G-CSF, compared with pegfilgrastim in reducing duration of severe neutropenia after chemotherapy for non-Hodgkin’s lymphoma.

Abstract

e19065 Background: G-CSF is used in patients at significant risk for developing severe neutropenia (neutrophil count < 0.5 × 109/L or grade 4 neutropenia) following myelosuppresive chemotherapy. GX-G3, human G-CSF fused to hyFc is a proposed alternative to Neulasta. Methods: An open-label, randomized, phase II study was designed to compare the effects of subcutaneous (SC) injection of GX-G3 (a long-acting G-CSF) at doses of 150, 250 and 350 μg/kg with Neulasta 6 mg administered SC in patients receiving R-CHOP for advanced NHL (n = 65). The primary objective was to assess the duration of severe neutropenia after 1st cycle of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (R-CHOP). The following parameters were also assessed: duration of severe neutropenia after 2nd cycle of chemotherapy, optimal time for GX-G3 intervention (two GX-G3 250 μg/kg cohorts; administered 24 and 72 hours after R-CHOP), incidence of severe neutropenia and febrile neutropenia post R-CHOP, pharmacokinetics, and safety. Patients were randomly assigned to receive GX-G3 or reference drug, Neulasta, one dose after 1st and 2nd cycle of R-CHOP for a total of 2 doses. Results: The mean duration of severe neutropenia after 1st cycle was shortest in GX-G3 350 μg/kg group [GX-G3 150, 250 (24h, 72h), 350 μg/kg and Neulasta®; 3.2, 2.3, 2.0, 1.3 and 2.4 days, respectively]. The results of all GX-G3 groups and Neulasta were not significantly different for duration of severe neutropenia after 2nd cycle of R-CHOP, incidence of severe neutropenia and febrile neutropenia, or toxicity profile. The elimination half-life of GX-G3 and Neulasta ranged from 29.8 to 66 hours and 19.2 to 76.8 hours, respectively. Conclusions: GX-G3, in all tested dosage regimen, was safe and well tolerated in this patient population. A single injection of GX-G3 per chemotherapy cycle provided neutrophil support with safety and efficacy similar to that provided by Neulasta. GX-G3 administration after 24 hours, compared to 72 hours post R-CHOP treatment resulted in relatively shorter duration of severe neutropenia. Clinical trial information: 2015-002693-20.