<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01688960</url>
  </required_header>
  <id_info>
    <org_study_id>R910-ST-1114</org_study_id>
    <nct_id>NCT01688960</nct_id>
  </id_info>
  <brief_title>Nesvacumab (REGN910/ SAR307746) and Aflibercept (&quot;Ziv-aflibercept&quot; in the U.S.) in Patients With Advanced Solid Malignancies</brief_title>
  <official_title>A Phase 1b Study of Combined Angiogenesis Inhibition by Administering REGN910 and Aflibercept (Ziv-aflibercept) in Patients With Advanced Solid Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Regeneron Pharmaceuticals</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, multicenter, ascending, multiple dose study of nesvacumab (REGN910/&#xD;
      SAR307746) in combination with aflibercept (&quot;ziv-aflibercept&quot; in the U.S.)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D)</measure>
    <time_frame>Day 1 to Day 28</time_frame>
    <description>Determine the maximum tolerable dose or recommended phase 2 dose of nesvacumab (REGN910/ SAR307746) administered in combination with aflibercept (ziv-aflibercept) in patients with advanced solid malignancies</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK)</measure>
    <time_frame>Day 1 to Day 170</time_frame>
    <description>To assess PK parameters such as concentration of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>Day 1 to Day 170</time_frame>
    <description>To assess the anti-drug antibodies of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor activity</measure>
    <time_frame>Day 1 to Day 170</time_frame>
    <description>Objective tumor response according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacodynamics (PD)</measure>
    <time_frame>Day 1 to Day 170</time_frame>
    <description>Target inhibition biomarker changes, serum tumor markers</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3b</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nesvacumab (REGN910/ SAR307746)</intervention_name>
    <description>Dose level 1</description>
    <arm_group_label>Cohort 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nesvacumab (REGN910/ SAR307746)</intervention_name>
    <description>Dose level 2</description>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3b</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nesvacumab (REGN910/ SAR307746)</intervention_name>
    <description>Dose level 3</description>
    <arm_group_label>Cohort 3a</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>aflibercept (ziv-aflibercept)</intervention_name>
    <description>Dose level 1</description>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 3a</arm_group_label>
    <other_name>In US: aflibercept is known as ziv-aflibercept</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>aflibercept (ziv-aflibercept)</intervention_name>
    <description>Dose level 2</description>
    <arm_group_label>Cohort 3b</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <other_name>In US: aflibercept is known as ziv-aflibercept</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Inclusion criteria include, but are not limited to, the following:&#xD;
&#xD;
          1. Confirmed diagnosis of solid tumor malignancy&#xD;
&#xD;
          2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1&#xD;
&#xD;
          3. Adequate hepatic, renal and bone marrow function&#xD;
&#xD;
          4. Resolution of toxicity from prior therapy (except alopecia) to grade less than or&#xD;
             equal to 1&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Exclusion criteria include, but are not limited to, the following:&#xD;
&#xD;
          1. Patients with brain metastases, spinal cord compression, carcinomatous meningitis, or&#xD;
             other evidence of central nervous system involvement&#xD;
&#xD;
          2. Either systolic BP greater than 140 mm Hg or diastolic BP greater than 90 mm Hg&#xD;
&#xD;
          3. Patients with medical history of myocardial infarction, unstable angina pectoris,&#xD;
             coronary/ peripheral artery bypass graft, congestive heart failure or ventricular&#xD;
             arrhythmia&#xD;
&#xD;
          4. Patients with deep vein thrombosis or pulmonary embolism within last 3 months&#xD;
&#xD;
          5. Patients with serious non healing wound or acute ulcer&#xD;
&#xD;
          6. Patients with treatment resistant or bleeding peptic ulcer disease, erosive&#xD;
             esophagitis or gastritis, grade 3 or gastrointestinal bleeding/hemorrhage, infectious&#xD;
             or inflammatory bowel disease, diverticulitis, or other uncontrolled thromboembolic&#xD;
             event within last 3 months&#xD;
&#xD;
          7. Patients with history of abdominal or tracheal-esophageal fistula&#xD;
&#xD;
          8. Prior treatment with aflibercept (ziv-aflibercept), Ang2 or Tie2 inhibitors&#xD;
&#xD;
          9. Prior treatment with bevacizumab within last 6 weeks&#xD;
&#xD;
         10. Pregnant or breast-feeding women&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trial Management</last_name>
    <role>Study Director</role>
    <affiliation>Regeneron Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New York</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toronto</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 17, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <last_update_submitted>March 16, 2015</last_update_submitted>
  <last_update_submitted_qc>March 16, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 17, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aflibercept</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01688960
org study id: R910-ST-1114
nct id: NCT01688960
lead sponsor: 
collaborator: 
has dmc: No
This is an open-label, multicenter, ascending, multiple dose study of nesvacumab (REGN910/
      SAR307746) in combination with aflibercept ("ziv-aflibercept" in the U.S.)
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerable Dose (MTD) or Recommended Phase 2 Dose (RP2D)
time frame: Day 1 to Day 28
description: Determine the maximum tolerable dose or recommended phase 2 dose of nesvacumab (REGN910/ SAR307746) administered in combination with aflibercept (ziv-aflibercept) in patients with advanced solid malignancies
measure: Pharmacokinetics (PK)
time frame: Day 1 to Day 170
description: To assess PK parameters such as concentration of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept).
measure: Immunogenicity
time frame: Day 1 to Day 170
description: To assess the anti-drug antibodies of nesvacumab (REGN910/ SAR307746) and aflibercept (ziv-aflibercept)
measure: Antitumor activity
time frame: Day 1 to Day 170
description: Objective tumor response according to RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1
measure: Pharmacodynamics (PD)
time frame: Day 1 to Day 170
description: Target inhibition biomarker changes, serum tumor markers
arm group label: Cohort 1
arm group type: Experimental
arm group label: Cohort 2
arm group type: Experimental
arm group label: Cohort 3a
arm group type: Experimental
arm group label: Cohort 3b
arm group type: Experimental
arm group label: Cohort 4
arm group type: Experimental
intervention type: Drug
intervention name: nesvacumab (REGN910/ SAR307746)
description: Dose level 1
arm group label: Cohort 1
intervention type: Drug
intervention name: nesvacumab (REGN910/ SAR307746)
description: Dose level 2
arm group label: Cohort 2
arm group label: Cohort 3b
intervention type: Drug
intervention name: nesvacumab (REGN910/ SAR307746)
description: Dose level 3
arm group label: Cohort 3a
arm group label: Cohort 4
intervention type: Drug
intervention name: aflibercept (ziv-aflibercept)
description: Dose level 1
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 3a
other name: In US: aflibercept is known as ziv-aflibercept
intervention type: Drug
intervention name: aflibercept (ziv-aflibercept)
description: Dose level 2
arm group label: Cohort 3b
arm group label: Cohort 4
other name: In US: aflibercept is known as ziv-aflibercept
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trial Management
role: Study Director
affiliation: Regeneron Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Aflibercept