A randomized, double-blind, active control, multicenter, dose-finding study of XM22, glycopegfilgrastim, in patients with breast cancer receiving myelosuppressive therapy.

Abstract

9080 Background: XM22 is a glyco-PEGylated r-metHuG-CSF that is being developed for the reduction of duration of severe neutropenia and incidence of febrile neutropenia in cancer patients undergoing chemotherapy. Randomized, single-blind studies in healthy volunteers have evaluated the pharmacokinetics, pharmacodynamics, and safety of long-acting, subcutaneously (sc) administered XM22 in comparison to Pegfilgrastim (PEGF). The primary objective of the XM22-02-INT study was to identify the optimal fixed dose of XM22 compared to PEGF in primary breast cancer patients receiving chemotherapy (CTX). Methods: This study was a multinational, multicenter, randomized, double-blind, controlled study evaluating the efficacy and safety of fixed doses of XM22 compared to 6 mg of PEGF in breast cancer patients receiving 4 cycles of doxorubicin 60 mg/m2 and docetaxel 75 mg/m2. XM22 (3 mg, 4.5 mg, or 6 mg) or PEGF (6mg) was administered sc approximately 24 hours after CTX on each of the 4 cycles. The primary endpoint was the duration of severe neutropenia (DSN) in cycle 1. Secondary endpoints included DSN in cycles 2-4, duration and incidence of severe neutropenia, febrile neutropenia, ANC values, ANC nadir, time to ANC nadir and recovery. Pharmacokinetic parameters were also analyzed. Results: A total of 229 patients were screened and 208 randomized to XM22 3mg (n=53), XM22 4.5mg (n=51), XM22 6mg (n=50), and PEGF (n=54). Six patients did not complete the study. Demographic and baseline characteristics were comparable across the treatment groups. DSN in cycle 1 was 1.1, 0.8, 0.8, and 0.9 days in the XM22 3mg, 4.5mg, 6mg and PEGF groups, respectively. Using multivariate Poisson regression for the primary endpoint, greater efficacy was seen with higher XM22 doses. Secondary endpoints also suggested greater efficacy with increased XM22 dose. Treatment-emergent adverse events were similar between the treatment groups. Conclusions: DSN in cycle 1 was similar for all treatment groups (mean = 0.9 days), however, there was a clear trend to shorter DSN with higher XM22 doses. The study supported the use of XM22 6 mg in the phase III comparative study versus PEGF.