An open-label, dose-escalating study of Maxy-G34, a novel potent, long-acting Pegylated G-CSF, compared with pegfilgrastim (PF) for the treatment of chemotherapy induced neutropenia (CIN)

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e14500 Background: rhG-CSF reduces the incidence and duration of CIN in patients (pts) receiving myelosuppressive chemotherapy. Maxy-G34 is a recombinant, modified human G-CSF, containing three 5 kD PEG groups. These modifications alter both renal and receptor mediated clearance, leading to a longer half-life and the potential for enhanced activity. Phase I studies demonstrated safety of Maxy-G34 in normal volunteers with a dose dependent rapidly reversible increase in the absolute neutrophil count (ANC). The effect of Maxy-G34 on CIN was evaluated in an open-label, active-comparator controlled, dose-ranging study. Methods: The primary efficacy endpoint was duration of severe, Grade 4 neutropenia (G4N) in treatment cycle 1. Adults with high-risk Stage I-IIIa breast cancer eligible for TAC chemotherapy received Maxy-G34 at 10, 30, 45, 60 or 100 μg/kg or the active control PF 6 mg, given sub- cutaneously 24-hours after each dose of TAC for 6 cycles. Blood samples were collected daily and analyzed at a central laboratory throughout each of the 21-day chemotherapy cycles to determine ANC and evaluate PK profile of Maxy-G34. Results: All dose groups of Maxy-G34 enrolled 6 pts each, except the 100 μg/kg group (3 pts), and the PF group (8 pts). The mean durations of G4N in cycle 1 were 2.2 days for 10 μg/kg, 1.8 days for 30 μg/kg, 0.8 days for 45 μg/kg, 2.2 days for 60 μg/kg, and 1.7 days for 100 μg/kg Maxy-G34 groups vs. 2.0 days for PF. The rate of FN was 2.6% across all Maxy-G34 doses vs. 4.2% for PF. CD34+ cell counts increased across Maxy-G34 groups following recovery from nadir with maximum concentration in treatment cycle 1 ranging from 25.8 to 133.3 cells/mL versus 49.6 cells/mL for PF. The average half-life and Cmax obtained after Maxy-G34 were approximately 2-fold higher than PF. Adverse events were consistent with those reported for G-CSF and TAC with no serious unexpected adverse events. Grade 3/4 AEs for Maxy-G34 was 9.5% vs. 8.5% for PF. No neutralizing antibodies related to Maxy-G34 were observed. Conclusion: Once-per-cycle Maxy-G34 appears to be effective in reducing CIN with no new safety signals. Further Phase II studies are planned. [Table: see text]

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