<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/NCT02221960</url>
  </required_header>
  <id_info>
    <org_study_id>D6050C00001</org_study_id>
    <nct_id>NCT02221960</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors</brief_title>
  <official_title>A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MedImmune LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MedImmune LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate MEDI6383 when given alone or together with MEDI4736 in adult subjects with&#xD;
      recurrent or metastatic solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study to&#xD;
      evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and&#xD;
      antitumor activity of MEDI6383 alone and in combination with MEDI4736 in adult subjects with&#xD;
      recurrent or metastatic solid tumors.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 15, 2014</start_date>
  <completion_date type="Actual">July 3, 2017</completion_date>
  <primary_completion_date type="Actual">July 3, 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety</measure>
    <time_frame>From time of informed consent through 12 weeks after last dose of investigational product</time_frame>
    <description>Primary endpoint will be the number (%) of subjects with adverse events and serious adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Preliminary Antitumor Activity</measure>
    <time_frame>Duration of Study</time_frame>
    <description>The endpoints for assessment of antitumor activity include objective response (OR), disease control (DC), duration of response (DoR), progression-free survival (PFS), and 3-year overall survival (OS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics of MEDI6383 or MEDI6383/MEDI4736</measure>
    <time_frame>From time of informed consent through 12 weeks after last dose of investigational product</time_frame>
    <description>When MEDI6383 is administered alone, the endpoints for assessment of PK of MEDI6383 include individual subject MEDI6383 concentrations in serum at different time points after MEDI6383 administration. When MEDI6383 is administered together with MEDI4736, the endpoints for assessment of PK of MEDI6383 and MEDI4736 include individual subject MEDI6383 and MEDI4736 concentrations in serum at different time points after MEDI6383 and MEDI4736 administration. PK Parameters that may be modeled may include Cmax, Area Under the concentration-time curve, Clearance, and terminal half-live.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker Activity</measure>
    <time_frame>From time of informed consent through 12 weeks after last dose of investigational product</time_frame>
    <description>The endpoints for assessment of pharmacodynamic activity include immunohistochemistry of tumor biopsies and assessment of tumor-infiltrating lymphocyte phenotypic markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>From time of informed consent through 12 weeks after last dose of investigational product</time_frame>
    <description>The endpoint for for the assessment of immunogenicity will include the number and percentage of subjects that develop anti-drug antibodies.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">39</enrollment>
  <condition>Recurrent or Metastatic Solid Tumors</condition>
  <arm_group>
    <arm_group_label>Monotherapy Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI6383</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI6383 and MEDI4736</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MEDI6383</intervention_name>
    <description>Subjects will receive MEDI6383 until disease progression or adverse event.</description>
    <arm_group_label>Monotherapy Arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MEDI6383 and MEDI4736</intervention_name>
    <description>Subjects will recieve MEDI6383 and MEDI4736 until disease progression or adverse event.</description>
    <arm_group_label>Combination Arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female subjects; age ≥ 18&#xD;
&#xD;
          2. Written informed consent must be obtained&#xD;
&#xD;
          3. Subjects must meet the following criteria:&#xD;
&#xD;
               1. Have recurrent or metastatic solid tumors&#xD;
&#xD;
               2. Must have received and have progressed, are refractory, or are intolerant to&#xD;
                  standard therapy appropriate for the specific tumor type. Subjects should not&#xD;
                  have received more than 5 prior lines of therapy for recurrent or metastatic&#xD;
                  disease including both standards of care and investigational therapies&#xD;
&#xD;
          4. Subjects must have at least 1 lesion&#xD;
&#xD;
          5. Subjects must consent to provide archived tumor specimens and / or tumor biopsy for&#xD;
             correlative biomarker studies.&#xD;
&#xD;
          6. Eastern Cooperative Oncology Group performance score of 0 or 1&#xD;
&#xD;
          7. In the opinion of the invesgator likely to complete ≥ 8 weeks of treatment.&#xD;
&#xD;
          8. Adequate organ function as determined by:&#xD;
&#xD;
             i. Absolute neutrophil count ≥ 1.5 x 109/L (1,500/mm3) ii.Platelet count ≥ 100 x 109/L&#xD;
             (100,000/mm3) iii.Hemoglobin ≥ 9.0 g/dL within first 2 weeks prior to first dose of&#xD;
             investigational product iv.Calculated creatinine clearance* (CrCl) or 24 hour urine&#xD;
             CrCl &gt; 50 mL/min v.Total bilirubin ≤ 1.5× ULN; for subjects with documented/suspected&#xD;
             Gilbert's disease, bilirubin ≤ 3× ULN vi.Aspartate transaminase (AST) and alanine&#xD;
             transaminase (ALT) ≤ 2.5× ULN vii.Serum Electrolytes within normal limits&#xD;
&#xD;
          9. Females of childbearing potential who are sexually active with a nonsterilized male&#xD;
             partner must use 2 methods of highly effective contraception from screening, and must&#xD;
             agree to continue using such precautions for 90 days after the final dose of&#xD;
             investigational product; 10) Nonsterilized males who are sexually active with a female&#xD;
             partner of childbearing potential must use a highly effective method of contraception&#xD;
             from Day 1 through 90 days after receipt of the final dose of investigational product&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR)&#xD;
             .&#xD;
&#xD;
          2. Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or&#xD;
             PD-1 antagonists are NOT permitted to enroll unless all of the following apply:&#xD;
&#xD;
               -  Must not have experienced a toxicity that led to permanent discontinuation of&#xD;
                  prior immunotherapy&#xD;
&#xD;
               -  All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or&#xD;
                  baseline prior to screening for this study.&#xD;
&#xD;
          3. Must not have experienced a ≥ Grade 3 AE or neurologic or ocular AE of any grade while&#xD;
             receiving prior immunotherapy&#xD;
&#xD;
          4. History of severe allergic reactions to any unknown allergens or any components of the&#xD;
             study drug formulations&#xD;
&#xD;
          5. Active or prior documented autoimmune disease within the past 2 years.&#xD;
&#xD;
          6. Untreated central nervous system metastatic disease l&#xD;
&#xD;
          7. Concurrent enrollment in another clinical study, unless it is an observational (non&#xD;
             interventional) clinical study or the follow-up period of an interventional study&#xD;
&#xD;
          8. Receipt of anticancer therapy within 28 days prior to the first dose of&#xD;
             Investigational Product&#xD;
&#xD;
          9. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer&#xD;
             treatment.&#xD;
&#xD;
         10. Unresolved toxicities from prior anticancer therapy&#xD;
&#xD;
         11. Systemic anticoagulation or daily aspirin dose exceeding 325 mg per day&#xD;
&#xD;
         12. Current or prior use of immunosuppressive medication within 14 days prior to the first&#xD;
             dose of MEDI6383. )&#xD;
&#xD;
         13. History of primary immunodeficiency, solid organ transplantation, or tuberculosis&#xD;
&#xD;
         14. True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C&#xD;
&#xD;
         15. Receipt of live, attenuated vaccine within 28 days prior to the first dose of&#xD;
             investigational products )&#xD;
&#xD;
         16. Pregnant or breastfeeding women&#xD;
&#xD;
         17. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of&#xD;
             MEDI6383 or still recovering from prior surgery. Local surgery of isolated lesions for&#xD;
             palliative intent is acceptable&#xD;
&#xD;
         18. Other invasive malignancy within 2 years&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medimmune Medimmune</last_name>
    <role>Study Director</role>
    <affiliation>MedImmune LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Parkville</city>
        <zip>3052</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <last_update_submitted>March 12, 2019</last_update_submitted>
  <last_update_submitted_qc>March 12, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Recurrent or metastatic solid tumors, MEDI6383, OX40</keyword>
  <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>Durvalumab</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/NCT02221960
org study id: D6050C00001
nct id: NCT02221960
lead sponsor: 
has dmc: No
To evaluate MEDI6383 when given alone or together with MEDI4736 in adult subjects with
      recurrent or metastatic solid tumors.
This is a Phase 1, multicenter, open-label, dose-escalation, and dose-expansion study to
      evaluate the safety, tolerability, pharmacokinetics, immunogenicity, pharmacodynamics, and
      antitumor activity of MEDI6383 alone and in combination with MEDI4736 in adult subjects with
      recurrent or metastatic solid tumors.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety
time frame: From time of informed consent through 12 weeks after last dose of investigational product
description: Primary endpoint will be the number (%) of subjects with adverse events and serious adverse events.
measure: Preliminary Antitumor Activity
time frame: Duration of Study
description: The endpoints for assessment of antitumor activity include objective response (OR), disease control (DC), duration of response (DoR), progression-free survival (PFS), and 3-year overall survival (OS)
measure: Pharmacokinetics of MEDI6383 or MEDI6383/MEDI4736
time frame: From time of informed consent through 12 weeks after last dose of investigational product
description: When MEDI6383 is administered alone, the endpoints for assessment of PK of MEDI6383 include individual subject MEDI6383 concentrations in serum at different time points after MEDI6383 administration. When MEDI6383 is administered together with MEDI4736, the endpoints for assessment of PK of MEDI6383 and MEDI4736 include individual subject MEDI6383 and MEDI4736 concentrations in serum at different time points after MEDI6383 and MEDI4736 administration. PK Parameters that may be modeled may include Cmax, Area Under the concentration-time curve, Clearance, and terminal half-live.
measure: Biomarker Activity
time frame: From time of informed consent through 12 weeks after last dose of investigational product
description: The endpoints for assessment of pharmacodynamic activity include immunohistochemistry of tumor biopsies and assessment of tumor-infiltrating lymphocyte phenotypic markers
measure: Immunogenicity
time frame: From time of informed consent through 12 weeks after last dose of investigational product
description: The endpoint for for the assessment of immunogenicity will include the number and percentage of subjects that develop anti-drug antibodies.
arm group label: Monotherapy Arm
arm group type: Experimental
description: MEDI6383
arm group label: Combination Arm
arm group type: Experimental
description: MEDI6383 and MEDI4736
intervention type: Biological
intervention name: MEDI6383
description: Subjects will receive MEDI6383 until disease progression or adverse event.
arm group label: Monotherapy Arm
intervention type: Biological
intervention name: MEDI6383 and MEDI4736
description: Subjects will recieve MEDI6383 and MEDI4736 until disease progression or adverse event.
arm group label: Combination Arm
criteria: 
gender: All
minimum age: 18 Years
maximum age: 99 Years
healthy volunteers: No
last name: Medimmune Medimmune
role: Study Director
affiliation: MedImmune LLC
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Durvalumab