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.
Neutropenia is a condition of an abnormally low number of neutrophils which render patients more susceptible to infections, especially to bacterial infections, as the condition may become life threatening and deadly without prompt medical attention. Various factors such as, anticancer drugs, radiotherapy, infectious diseases, congenital defects, or vitamin B12/B9 deficiency can trigger neutropenia. GX‐G3, a human hybrid (hy) Fc‐fused granulocyte colony stimulating factor (G‐CSF), was developed as next‐generation G‐CSF for the treatment of cancer therapy‐induced neutropenia. In this study, with the aim of investigating this promising potential next‐generation G‐CSF, comparative pharmacokinetic and pharmacodynamic studies were conducted in healthy and neutropenia‐induced rats. It was found that t1/2 of GX‐G3 is longer than same mass injection of filgrastim and pegfilgrastim and AUEClast (area under theeffect‐time curve from time zero to the last measurable ANC level) of absolute neutrophil count showed a significant increase after GX‐G3 injection compared with filgrastim and pegfilgrastim in healthy rats. Besides, in duration of neutropenia after the same mass injection GX‐G3 showed about 3.3 days of reduction effect compared with that of filgrastim, and 1.3 days of reduction effect compared with that of pegfilgrastim in neutropenia‐induced rats. These results demonstrate that the half‐life of GX‐G3 is longer than pegfilgrastim and GX‐G3 is more effective than filgrastim and pegfilgrastim in neutropenia‐induced rats.
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