A phase Ib dose escalation study of vantictumab (VAN) in combination with nab-paclitaxel (Nab-P) and gemcitabine (G) in patients with previously untreated stage IV pancreatic cancer.

249Background: Vantictumab is a fully human monoclonal antibody that inhibits Wnt pathway signaling through binding FZD1, 2, 5, 7, and 8 receptors. A phase Ib study of VAN in combination with Nab-P and G was performed in patients with untreated stage IV pancreatic adenocarcinoma. Methods: Patients received VAN at escalating doses (3-7 mg/kg) in combination with standard dosing of Nab-P and G according to a 3+3 design. Due to fragility fractures occurring in this and other related clinical trials, dosing on an every 2 week schedule in cohorts 1 and 2 was transitioned to every 4 week dosing for cohorts 3 through 5. In these later cohorts, a minimum of six patients were treated at each dose level and additional criteria for maximum tolerated dose (MTD) integrating bone safety parameters were added. The bone safety plan was also revised for these cohorts. Sequential dosing of VAN followed by Nab-P and G was explored in cohort 5. Results: Thirty-one patients (52% male, 48% female) were enrolled and treated in ...