Background: The vascular endothelial growth factor C (VEGFEC) induces angiogenesis via activation of both VEGFRE2 and VEGFRE3, as well as lymphangiogenesis via activation of VEGFRE3. VGX-100 is a novel fully human IgG₁λ neutralizing monoclonal antibody directed against human VEGFEC. Synergism between the VEGF-A inhibitor, bevacizumab and VGX-100 has been documented pre-clinically. It is thought that tumoral escape and relapse following VEGF-A inhibition, may in part be due to increased VEGF-C that signals through VEGFR-2 and VEGFR-3. Therefore the premise of this study is that administration of VGX-100 in conjunction with bevacizumab would block the two key ligands for VEGFRE2 along with blocking VEGFR-3-mediated tumor angiogenesis and lymphangiogenesis, and thus this drug combination will be clinically synergistic. This study (NCT01514123) is enrolling at MD Anderson and UCLA. Methods: Objectives:establish the safety and toxicity, MTD, pharmacokinetic and pharmacodynamic / biomarker profiles, as well as preliminary anti-tumor activity in refractory pts. Eligibility: pts with advanced solid tumors, good organ function, ECOG PS 0-1, any number of prior therapies, no CNS or cerebrovascular haemorrhage, no MI or reversible posterior leukoencephalopathy syndrome associated with prior anti-VEGF/anti-VEGFR therapy. Design: This is an open-label phase I dose escalation study with a standard “3+3” design. The study has two arms: safety data from the 28 day DLT period from Arm A (VGXE100 monotherapy at 6 cohort dose levels: 1, 2.5, 5, 10, 20 and 30 mg/kg, QW) will be available prior to starting the equivalent dose level in Arm B (VGXE100 at 5 cohort dose levels: 2.5, 5, 10, 20 and 30 mg/kg QW with bevacizumab at doses of either 5 or 10 mg/kg, Q2W). Accrual has completed in Cohorts A1 to A5 and B1 to B2. Accrual is underway for Cohort A6 and B3. Clinical trial information: NCT01514123.