Study of VGX-100 Administered Alone and Co-administered With Bevacizumab in Adult Subjects With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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A Phase I, Open Label, Dose Escalation Study of the VEGF-C Human Monoclonal Antibody VGX-100 Administered by Intravenous Infusion Alone and Co-administered With Bevacizumab in Adult Subjects With Advanced or Metastatic Solid Tumors

Conditions
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Neoplasms, Cancer

Intervention / Treatment
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* Drug: VGX-100
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A - VGX-100 alone<br>Dose escalation of VGX-100 monotherapy | Drug: VGX-100<br>* VGX-100 will be administered by IV infusion once every week<br>|
| Experimental: Arm B - VGX-100 plus bevacizumab<br>Dose escalation of VGX-100 in combination with escalating doses of bevacizumab | Drug: VGX-100<br>* VGX-100 will be administered by IV infusion once every week<br>Drug: Bevacizumab<br>* Bevacizumab will be administered by IV infusion once every 2 weeks<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of adverse events including dose limiting toxicities |  | Approximately 16 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response by RECIST criteria | Tumor response assessment will be measured by computated tomography (CT) or Magnetic resonance imaging (MRI) every 8 or 12 weeks throughout the study | Approximately 16 months | 
| Pharmacokinetic parameters of VGX-100 alone and co-administered with bevacizumab including Cmax, Cmin, AUC and if feasible half life (t1/2) |  | 28 days after the last subject in each cohort | 
| Anti-VGX-100 antibody formation |  | Approximately 16 months | 
| Biomarker levels including VEGF-A, VEGF-C, VEGF-D, soluble VEGFR-2, and soluble VEGFR-3 |  | Approximately 16 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VGX-100, Bevacizumab, VEGF-C, First-In-Human, Dose Escalation, Advanced Solid Tumors, Angiogenesis Inhibitors, Angiogenesis Modulating Agents, Pharmacologic Actions, Antibodies, Monoclonal, Phase 1, Oncology, Advanced malignancy