Pharmacokinetics (PK) and pharmacodynamics (PD) of AMG 162, a fully human monoclonal antibody to Receptor Activator of NF kappa B Ligand (RANKL), following a single subcutaneous dose to patients with cancer-related bone lesions

8106 Background: RANKL is an essential osteoclastic differentiation/activation factor. AMG 162 PK and PD were evaluated in a phase 1, single dose, randomized, double-blind, double-dummy, active control (pamidronate), dose escalation study, in patients with breast cancer (BC) or multiple myeloma (MM), with lytic or mixed lytic-blastic bone lesions. Methods: Patients (n=54; 3–9/cohort) received a subcutaneous (SC) injection of either AMG 162 (0.1, 0.3, 1.0, or 3.0 mg/kg) or placebo (3:1 ratio) and an intravenous infusion of either 90 mg of pamidronate or saline. Blood and urine samples were collected for determinations of AMG 162 serum concentrations and the bone resorption marker, N-telopeptide levels (uNTx/Cr), respectively. Results: AMG 162 serum levels reached average maximums of 448 ng/mL (0.1 mg/kg) to 19,800 ng/mL (3.0 mg/kg) 14 to 21 days post-dose, and 625 ng/mL (0.1 mg/kg) to 20,100 ng/mL (3.0 mg/kg) 7 to 14 days post-dose in BC and MM patients, respectively. Serum levels were maintained above 100...