Volociximab is a chimeric IgG(4) that is being developed as a novel first-in-class anti-angiogenic, α(5)β(1) integrin inhibitor for the treatment of solid tumors. A mechanism-based pharmacokinetic (PK)/pharmacodynamic (PD) model was developed to investigate the dynamic interaction between volociximab concentrations and free monocyte α(5)β(1) integrin levels in cancer patients. Twenty-one cancer patients from six dose cohorts (0.5, 1.0, 2.5, 5.0, 10, and 15 mg/kg) were included in the analysis. The fully integrated receptor-binding PK/PD model was developed and fit simultaneously to the PK/PD data. A Monte-Carlo parametric expectation-maximization method implement in S-ADAPT program was used to obtain estimates of population parameters and inter- and intra-subject variability. The PK/PD time profiles were well described by the model and the parameters were estimated with good precision. The model was used to simulate PK/PD time profiles for multiple dose regimens at various dose levels, and the results suggested that the monocyte α(5)β(1) integrin binding was saturated (≤5% free) at week 16 in the majority of patients treated with volociximab doses ≥10 mg/kg IV every 2 weeks. The developed model is useful for anticipating the drug exposures and extent of volociximab binding to peripheral monocyte α(5)β(1) integrin in untested regimens and for optimizing the design of future clinical trials.