A phase I dose escalation and pharmacokinetic (PK) study of intravenous (iv) aflibercept (VEGF Trap) plus docetaxel (D) and cisplatin (C) in patients (pts) with advanced solid tumors: preliminary results

14539 Background: Aflibercept (AF), a potent inhibitor of vascular endothelial growth factor, is a recombinant fusion molecule of the human VEGF receptor R1 + R2 (Flt-1, KDR) extracellular domains and the Fc portion of human IgG1. AF binds VEGF-A and neutralizes all VEGF-A isoforms plus placental growth factor. This study was designed to assess the safety, dose limiting toxicities (DLTs)/recommended dose (RD) and PK of AF + DC. Methods: This combination trial explored escalating iv doses of AF followed by fixed dose of D then C (each 75 mg/m2) every 3 weeks (q3w). Treatment cohorts consisted of at least 3 pts up to 6 pts in case of DLT. Results: 16 heavily pretreated pts (Male/Female 3/13, median age 55 [39–76], ECOG-PS 0/1: 9/7) were enrolled in 3 AF dose levels (4.0, 5.0 and 6.0 mg/kg). Pts’ cancers included breast (5), ovarian (5), colon (2) and others (4). Pts received a median number of 4 [2–8] treatment cycles (cy). DLTs were only hematological (febrile neutropenia at cy 1) for 1/6 pts at AF 4.0 mg/...