This is a non-randomized, multi-dose, first-in-human, multicenter, two arm (Arm A: VGX-100 alone; Arm B: VGX-100 co-administered with bevacizumab), open label, dose escalation study in subjects with advanced or metastatic solid tumors. The study is aimed at evaluating the safety and establishing the recommended dose of the VEGF-C human monoclonal antibody VGX-100 when administered alone or in combination with bevacizumab.

Inclusion Criteria:

• Age ≥ 18 years
• Provision of written informed consent
• Histologically or cytologically documented advanced or metastatic solid tumor that is refractory to standard treatment, for which no standard therapy is available, or for which the subject refuses standard therapy
• Life expectancy > 3 months in the opinion of the investigator
• ECOG performance status 0 to 1
• Evaluable OR measurable disease by RECIST 1.1 criteria
• Agree to the use of effective contraceptive if either male or female of child bearing potential

Exclusion Criteria:

• Inadequate venous access

• Women who are lactating/breastfeeding

• Women with a positive pregnancy test or who are planning to become pregnant during the duration of the study

• Known to be HIV positive, or have chronic hepatitis B or C

• Major surgical procedure within 6 weeks of Baseline or surgical or other wound that is not fully healed at Baseline

• Untreated or symptomatic brain metastasis, known central nervous system metastasis, or spinal cord compression (except glioblastoma multiforme)

• Mediastinal or cavitated, or lung mass located near, invading or encasing a major blood vessel or airway on imaging

• Squamous cell lung cancer

• History of or known/suspected gastrointestinal perforation

• Hemoptysis of >2.5 mL (half a teaspoon) red blood within 28 days of Screening

• Deep venous thrombosis or history of symptomatic pulmonary thromboembolism within 6 months of Screening

• Gastrointestinal bleeding requiring medical intervention within 28 days of Screening

• Receipt of therapeutic concentrations of warfarin or other anticoagulants within 7 days of Screening

• Receipt of investigational agent(s) for any indication within 28 days of Baseline or 5 half lives, whichever is greater

• Receipt of the following treatments:

  • Traditional cytotoxics, tyrosine kinase inhibitors or other small molecule anti-cancer agents within 21 days
  • Nitrosoureas, mitomycin C, bevacizumab or trastuzumab within 6 weeks
  • Any other therapeutic monoclonal antibodies within 21 days
  • Hormonal therapy (other than gonadal suppression) within 14 days

• Radiotherapy:

  • to >25% bone marrow
  • to brain within 28 days of baseline
  • other than above within 14 days of baseline

• Unstable angina, myocardial infarction, transient ischemic events, or stroke within 24 weeks of Screening

• History of CNS hemorrhage, cerebrovascular hemorrhage, myocardial infarction or reversible posterior leukoencephalopathy syndrome associated with prior anti-VEGF/anti-VEGFR therapy

• Uncontrolled hypertension of ≥ CTCAE Grade 2

• Proteinuria at Baseline of ≥2+ or 1.0g/24 hours

• Prior allergic reaction to a monoclonal antibody