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

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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Cancer
• Intervention / Treatment: Drug: VGX-100; Drug: Bevacizumab

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • UCLA Hematology-Oncology
  • Texas
    • Houston, Texas, United States, 77030
      • UT MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Circadian Technologies Ltd.
• Investigators: Study Director: Clinical Research, Circadian Technologies

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 29, 2011
• Primary Completion (ACTUAL): February 7, 2014
• Study Completion (ACTUAL): November 16, 2017

Study Registration Dates

• First Submitted: January 12, 2012
• First Submitted That Met QC Criteria: January 19, 2012
• First Posted (ESTIMATE): January 20, 2012

Study Record Updates

• Last Update Posted (ACTUAL): September 17, 2020
• Last Update Submitted That Met QC Criteria: September 16, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Bevacizumab; Phase 1; Oncology; Advanced Solid Tumors; Antibodies, Monoclonal; Pharmacologic Actions; Dose Escalation; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; First-In-Human; VEGF-C; VGX-100; Advanced malignancy
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: VGX-100-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED