The identification of patients who are most likely to benefit from therapy is an important component of any drug development strategy. Ideally, baseline characteristics are used to select patients but that is not always the case. Placental growth factor (PLGF) was a pharmacodynamic (PD) biomarker for an investigational compound AMG 706 (motesanib), which is a selective oral inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3, the platelet-derived growth factor (PDGF) receptor and Kit. Data generated from earlier phase studies that suggested that higher levels of PLGF after one cycle of dosing compared with baseline was associated with improved patient benefit. Considerations that triggered the decision to test the hypothesis that PLGF was a therapeutic response biomarker (i.e., whether a patient should remain on therapy) in a phase 3 trial will be presented.