PRO131921 is a third-generation, humanized anti-CD20
monoclonal antibody with increased antibody-dependent cytotoxicity and
complement-dependent cytotoxicity compared to
rituximab. In this phase I study,
PRO131921 was administered as a single agent to patients with CD20+, relapsed or refractory, indolent
non-Hodgkin lymphoma (NHL) who had been treated with a prior
rituximab-containing regimen. The primary aim of this study was safety and tolerability of
PRO131921. The secondary aim of the study, and focus of this report, was to determine the pharmacokinetics (PK) profile of
PRO131921 and establish a correlation between
drug exposure and clinical efficacy. Patients were treated with
PRO131921 by
intravenous infusion weekly for 4 weeks and the dose was escalated based on safety in a 3+3 design. Twenty-four patients were treated with
PRO131921 at doses from 25mg/m(2) to 800 mg/m(2). Analysis of PK data demonstrated a correlation between higher normalized
drug exposure (normalized AUC) and
tumor shrinkage (p = .0035). Also, normalized AUC levels were higher among responders and subjects displaying
tumor shrinkage versus subjects progressing or showing no regression (p = 0.030). In conclusion,
PRO131921 demonstrated clinical activity in
rituximab-relapsed and refractory indolent NHL patients. The observation that higher normalized AUC may be associated with improved clinical responses has potential implications in future trials of
monoclonal antibody-based
therapies, and emphasizes the importance of early PK studies to optimize antibody efficacy.