A phase I dose escalation (DE) and pharmacokinetics (PK) study of intravenous aflibercept (VEGF Trap) plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in patients with advanced solid tumors (STs)

3557 Background: Aflibercept (AF), a recombinant fusion molecule of the human VEGF receptor extracellular domains and the Fc portion of human IgG1, is a potent inhibitor of vascular endothelial growth factor. This study assessed the safety, dose limiting toxicities (DLTs)/recommended dose (RD) and PK of AF+I-LV5FU2. Methods: DE of AF followed by I-LV5FU2 (fixed standard dose) every 2 weeks (q2w) were explored. Results: 38 pts were enrolled (M/F: 18/20, median age 53 [19–77], ECOG PS 0/1: 24/13) including colorectal (23) and ovarian (5) cancers. Thirty six pts received prior chemotherapy (CT): median 3 [1–5]. A total of 404 cycles (median 10 [1–26]) of AF+I- LV5FU2 were administered across 4 AF dose levels (DL) ranging from 2.0 to 6.0 mg/kg. DLTs were: 2/12 pts at 4.0 (Grade (Gr) 3 proteinuria (PrU)>2wks including 1 pt with thrombotic microangiopathy), 2/10 pts at 5.0 (Gr 3 stomatitis and esophageal reflux) and 2/12 pts at 6.0 mg/kg (febrile neutropenia, Gr 3 stomatitis). The main AF-related Gr3–4 toxiciti...