Validation of the selected dose of aflibercept (VEGF Trap) plus irinotecan, 5-fluorouracil, and leucovorin (I-LV5FU2) in a phase I clinical trial of patients (pts) with advanced solid tumors (STs): Preliminary results

Abstract

14540 Background: Aflibercept (AF), a potent angiogenesis inhibitor fusion protein, is comprised of human VEGF receptor VEGFR1 (Flt-1) and VEGFR2 (Flk-1) extracellular domains fused to the Fc portion of human IgG1. A phase I dose escalation study established the AF 4.0 mg/kg + I-LV5FU2 (standard dose) every 2 weeks (q2w) as the recommended dose to be confirmed in a feasibility study. Methods: This was a randomized, double blind feasibility study of AF (4.0 mg/kg) or placebo + I-LV5FU2 at cycle 1, followed in subsequent cy by AF (4.0 mg/kg) + I-LV5FU2 q2w in pts with solid tumors. Study endpoints were to confirm the AF dose, explore the safety, preliminary efficacy and antivascular activity (DCE MRI) of AF. DCE MRI was performed at cycle 1 and 2, all imagings were centrally reviewed. Results: 27 pts were treated in both arms (15 male/12 female), median age 54 [39–75], ECOG PS 0/1/2: 12/11/4, with 70% of colorectal cancers. All pts received prior chemotherapy (CT): median 3 [1–6], 21 pts were previously tre...