<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/NCT02991911</url>
  </required_header>
  <id_info>
    <org_study_id>D9320C00001</org_study_id>
    <nct_id>NCT02991911</nct_id>
  </id_info>
  <brief_title>A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer</brief_title>
  <acronym>MEDI3726</acronym>
  <official_title>A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.</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>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to assess the safety and tolerability, describe the&#xD;
      dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum&#xD;
      administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI3726 in&#xD;
      subjects with mCRPC who have received prior treatment with abiraterone or enzalutamide, with&#xD;
      or without a prior taxane-based chemotherapy in the mCRPC setting.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 6, 2017</start_date>
  <completion_date type="Actual">September 30, 2019</completion_date>
  <primary_completion_date type="Actual">September 30, 2019</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Occurrence of adverse events (AEs)</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
    <description>Safety Endpoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of serious adverse events (SAEs)</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
    <description>Safety Endpoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Occurrence of dose-limiting toxicities (DLTs)</measure>
    <time_frame>From time of first dose through 21 days after first dose of MEDI3726</time_frame>
    <description>Safety Endpoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with changes in laboratory parameters from baseline</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
    <description>Safety Endpoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with changes in vital signs from baseline</measure>
    <time_frame>From time of informed consent through 21 days after last dose of MEDI3726</time_frame>
    <description>Safety Endpoint</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with changes in electrocardiogram (ECG) results from baseline</measure>
    <time_frame>From time of informed consent through 21 days after last dose of MEDI3726</time_frame>
    <description>Safety Endpoint</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response Evaluation Criteria in Solid Tumors (RECIST) response</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
    <description>Response according to RECIST version 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PSA50 response</measure>
    <time_frame>From time of fist dose through at least 12 weeks after first dose of MEDI3726</time_frame>
    <description>Reduction in PSA level of 50% (PSA50) or more compared with baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Circulating Tumor Cell (CTC) response</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
    <description>Conversion in the CTC count defined as a reduction from ≥ 5 cells/7.5 mL blood to &lt; 5 cells/7.5 mL blood with a confirmatory assessment at least 4 weeks later</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of MEDI3726 in combination with Enzalutamide</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide</time_frame>
    <description>Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEDI3726 plasma concentrations for pharmacokinetics (PK)</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEDI3726 maximum observed concentration for PK</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEDI3726 area under the concentration-time curve for PK</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEDI3726 clearance for PK</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MEDI3726 terminal half-life for PK</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number and percentage of subjects who develop anti-drug antibodies (ADAs)</measure>
    <time_frame>From time of informed consent through 90 days after last dose of MEDI3726</time_frame>
    <description>To determine the immunogenicity of MEDI3726</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Metastatic Castration Resistant Prostate Cancer</condition>
  <arm_group>
    <arm_group_label>Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI3726 Post-Chemo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI3726 Pre-Chemo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MEDI3726 &amp; Enzalutamide Combo</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MEDI3726 Post-Chemo</intervention_name>
    <description>Single agent MEDI3726 after abiraterone or enzalutatmide, with a prior taxane-based chemotherapy in the mCRPC setting</description>
    <arm_group_label>Arm A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MEDI3726 Pre-Chemo</intervention_name>
    <description>Single agent MEDI3726 after abiraterone or enzalutatmide, without a prior taxane-based chemotherapy in the mCRPC setting</description>
    <arm_group_label>Arm B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MEDI3726 &amp; Enzalutamide Combo</intervention_name>
    <description>MEDI3726 in combination with Enzalutatmide after prior treatment with abiraterone, with or without a prior taxane-based chemotherapy in the mCRPC setting</description>
    <arm_group_label>Arm C</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 18 years at the time of screening.&#xD;
&#xD;
          -  Histologically confirmed diagnosis of metastatic castration-resistant prostate&#xD;
             adenocarcinoma (mCRPC).&#xD;
&#xD;
          -  Documented PD in subjects with mCRPC as assessed by the Investigator and defined by at&#xD;
             least one of the following according to the PCWG3 criteria:&#xD;
&#xD;
               1. Radiographic progression.&#xD;
&#xD;
               2. PSA progression.&#xD;
&#xD;
          -  Prior exposure to abiraterone or enzalutamide of at least 12 weeks in the mCRPC&#xD;
             setting.&#xD;
&#xD;
        NOTE: Subjects who have received both abiraterone and enzalutamide in the mCRPC setting are&#xD;
        eligible.&#xD;
&#xD;
          -  In dose escalation: Prior taxane-based chemotherapy in the mCRPC setting is:&#xD;
&#xD;
               1. Required for Arm A.&#xD;
&#xD;
               2. Excluded for Arm B.&#xD;
&#xD;
               3. Optional for Arm C.&#xD;
&#xD;
                  Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with neuroendocrine, neuroendocrine differentiation and/or small cell&#xD;
             prostate cancer.&#xD;
&#xD;
          -  The subject has received any conventional or investigational anti-cancer treatment&#xD;
             within 21 days before the first dose of investigational product, with the following&#xD;
             modifications:&#xD;
&#xD;
               1. At least 14 days before the first dose of investigational product since&#xD;
                  completion of treatment with abiraterone or enzalutamide&#xD;
&#xD;
               2. At least 14 days before the first dose of investigational product since&#xD;
                  completion of prior taxane-based chemotherapy&#xD;
&#xD;
               3. At least 28 days before the first dose of investigational product since&#xD;
                  completion of treatment with Radium-223.&#xD;
&#xD;
               4. At least 42 days before the first dose of investigational product since&#xD;
                  completion of prior bicalutamide and nilutamide treatment.&#xD;
&#xD;
        NOTE: An LHRH agonist or antagonist required for ongoing testosterone suppression will be&#xD;
        permitted if Inclusion Criterion is satisfied.&#xD;
&#xD;
          -  Prior exposure to PSMA-directed therapies.&#xD;
&#xD;
          -  Subjects with previous radiotherapy for the treatment of unresectable, locally&#xD;
             advanced or metastatic prostate cancer are excluded if:&#xD;
&#xD;
               1. More than 25% of marrow-bearing bone has been irradiated.&#xD;
&#xD;
               2. The last fraction of radiotherapy has been administered within approximately 2&#xD;
                  weeks prior to the first dose of investigational product.&#xD;
&#xD;
          -  Brain metastases that are untreated, symptomatic, or require therapy to control&#xD;
             symptoms; or any radiation, surgery, or other therapy to control symptoms from brain&#xD;
             metastases within 2 months prior to the first dose of investigational product.&#xD;
&#xD;
          -  Subjects with known history of peripheral vasculopathies including, but not limited&#xD;
             to, macro and microangiopathies secondary to diabetes, peripheral arteriopathy of any&#xD;
             cause, intermittent claudication, repeated and/or non-healing ulcers of any cause.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MedImmune LLC</last_name>
    <role>Study Director</role>
    <affiliation>Sponsor GmbH</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Norfolk</city>
        <state>Virginia</state>
        <zip>23502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chur</city>
        <zip>7000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>London</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 9, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>January 14, 2020</last_update_submitted>
  <last_update_submitted_qc>January 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>metastatic, prostate cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prostatic Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>MEDI3726</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/NCT02991911
org study id: D9320C00001
nct id: NCT02991911
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the safety and tolerability, describe the
      dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum
      administered dose (MAD [in the absence of establishing the MTD]) for single agent MEDI3726 in
      subjects with mCRPC who have received prior treatment with abiraterone or enzalutamide, with
      or without a prior taxane-based chemotherapy in the mCRPC setting.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Occurrence of adverse events (AEs)
time frame: From time of informed consent through 90 days after last dose of MEDI3726
description: Safety Endpoint
measure: Occurrence of serious adverse events (SAEs)
time frame: From time of informed consent through 90 days after last dose of MEDI3726
description: Safety Endpoint
measure: Occurrence of dose-limiting toxicities (DLTs)
time frame: From time of first dose through 21 days after first dose of MEDI3726
description: Safety Endpoint
measure: Number of patients with changes in laboratory parameters from baseline
time frame: From time of informed consent through 90 days after last dose of MEDI3726
description: Safety Endpoint
measure: Number of patients with changes in vital signs from baseline
time frame: From time of informed consent through 21 days after last dose of MEDI3726
description: Safety Endpoint
measure: Number of patients with changes in electrocardiogram (ECG) results from baseline
time frame: From time of informed consent through 21 days after last dose of MEDI3726
description: Safety Endpoint
measure: Response Evaluation Criteria in Solid Tumors (RECIST) response
time frame: From time of informed consent through 90 days after last dose of MEDI3726
description: Response according to RECIST version 1.1
measure: PSA50 response
time frame: From time of fist dose through at least 12 weeks after first dose of MEDI3726
description: Reduction in PSA level of 50% (PSA50) or more compared with baseline
measure: Circulating Tumor Cell (CTC) response
time frame: From time of informed consent through 90 days after last dose of MEDI3726
description: Conversion in the CTC count defined as a reduction from ≥ 5 cells/7.5 mL blood to < 5 cells/7.5 mL blood with a confirmatory assessment at least 4 weeks later
measure: Safety and tolerability of MEDI3726 in combination with Enzalutamide
time frame: From time of informed consent through 90 days after last dose of MEDI3726 with enzalutamide
description: Measured by occurrence of AEs, SAEs, DLTs and number of patients with changes in laboratory parameters, vital signs, and ECG results from baseline
measure: MEDI3726 plasma concentrations for pharmacokinetics (PK)
time frame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 maximum observed concentration for PK
time frame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 area under the concentration-time curve for PK
time frame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 clearance for PK
time frame: From time of informed consent through 90 days after last dose of MEDI3726
measure: MEDI3726 terminal half-life for PK
time frame: From time of informed consent through 90 days after last dose of MEDI3726
measure: Number and percentage of subjects who develop anti-drug antibodies (ADAs)
time frame: From time of informed consent through 90 days after last dose of MEDI3726
description: To determine the immunogenicity of MEDI3726
arm group label: Arm A
arm group type: Experimental
description: MEDI3726 Post-Chemo
arm group label: Arm B
arm group type: Experimental
description: MEDI3726 Pre-Chemo
arm group label: Arm C
arm group type: Experimental
description: MEDI3726 & Enzalutamide Combo
intervention type: Biological
intervention name: MEDI3726 Post-Chemo
description: Single agent MEDI3726 after abiraterone or enzalutatmide, with a prior taxane-based chemotherapy in the mCRPC setting
arm group label: Arm A
intervention type: Biological
intervention name: MEDI3726 Pre-Chemo
description: Single agent MEDI3726 after abiraterone or enzalutatmide, without a prior taxane-based chemotherapy in the mCRPC setting
arm group label: Arm B
intervention type: Biological
intervention name: MEDI3726 & Enzalutamide Combo
description: MEDI3726 in combination with Enzalutatmide after prior treatment with abiraterone, with or without a prior taxane-based chemotherapy in the mCRPC setting
arm group label: Arm C
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: MedImmune LLC
role: Study Director
affiliation: Sponsor GmbH
facility: 
facility: 
facility: 
facility: 
facility: 
country: Switzerland
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Prostatic Neoplasms
mesh term: MEDI3726