<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/NCT02248805</url>
  </required_header>
  <id_info>
    <org_study_id>CP-MGD007-01</org_study_id>
    <nct_id>NCT02248805</nct_id>
  </id_info>
  <brief_title>Phase 1 Study of MGD007 in Relapsed/Refractory Metastatic Colorectal Carcinoma</brief_title>
  <official_title>A Phase 1, First-in-Human, Open Label, Dose Escalation Study of MGD007, A Humanized gpA33 x CD3 DART® Protein in Patients With Relapsed/Refractory Metastatic Colorectal Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MacroGenics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>MacroGenics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary goal of this Phase 1 study is to characterize the safety and tolerability of&#xD;
      MGD007 and establish the maximum tolerated dose (MTD) and schedule of MGD007 administered to&#xD;
      patients with metastatic colorectal carcinoma. Pharmacokinetics, pharmacodynamics, and the&#xD;
      anti-tumor activity of MGD007 will also be assessed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, multi-center, Phase 1 dose-escalation study to define a MTD, describe&#xD;
      preliminarily safety, and to assess PK, immunogenicity, and potential anti-tumor activity of&#xD;
      MGD007 in patients with relapsed or refractory metastatic colorectal cancer.&#xD;
&#xD;
      In the initial phase of the study, two dose schedules will be assessed in dose escalation,&#xD;
      once weekly and once every three weeks administration of single agent MGD007. Following the&#xD;
      establishment of an MTD, additional patients will enroll in four separate dose expansion&#xD;
      cohorts to further optimize the dose and schedule of MGD007 administration.&#xD;
&#xD;
      In all segments of the study, patients who benefit from MGD007 treatment and continue to meet&#xD;
      eligibility may continue treatment in Cycles 2 and beyond.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2014</start_date>
  <completion_date type="Actual">July 2, 2018</completion_date>
  <primary_completion_date type="Actual">July 2, 2018</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>Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule</measure>
    <time_frame>Cycle 1 of a 6 week cycle</time_frame>
    <description>Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit. The MTD will be defined separately for both the weekly and every three week schedules of MGD007 administration, and will be determined as the highest dose level at which the incidence of DLT is &lt; 33% during the first cycle of MGD007 treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Characterize the PK and Immunogenicity of MGD007</measure>
    <time_frame>Beginning of treatment through end of treatment, an expected duration of less than 12 months</time_frame>
    <description>Serum concentrations of MGD007 will be monitored. PK modeling will be performed and an appropriate model will be selected to describe the data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Describe any evidence of anti-tumor activity</measure>
    <time_frame>Every 6 weeks until End of Study, an expected duration of less than 12 months</time_frame>
    <description>Obtain regular radiographic and clinical evaluations to assess treatment response.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">95</enrollment>
  <condition>Colorectal Carcinoma</condition>
  <arm_group>
    <arm_group_label>Does Escalation Arm A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MGD007 treatment once weekly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Escalation Arm B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MGD007 treatment once every 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion Arm C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MGD007 once every 3 weeks for K-ras wild-type and mutant metastatic CRC</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Expansion Arms</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MGD007 2, 3, 6, or 12 doses/cycle</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MGD007</intervention_name>
    <description>MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a DART molecule. MGD007 will be administered as a single agent.</description>
    <arm_group_label>Does Escalation Arm A</arm_group_label>
    <arm_group_label>Dose Escalation Arm B</arm_group_label>
    <arm_group_label>Dose Expansion Arm C</arm_group_label>
    <arm_group_label>Dose Expansion Arms</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  For the dose escalation cohorts, histologically-proven metastatic colorectal&#xD;
             adenocarcinoma that is refractory to 2 prior standard treatment regimens or standard&#xD;
             treatment was declined.&#xD;
&#xD;
          -  For the dose expansion cohorts, histologically-proven metastatic colorectal&#xD;
             adenocarcinoma that is refractory to 1 prior standard treatment regimen or standard&#xD;
             therapy was declined.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
          -  Intolerance to at least 2 prior standard therapy regimens&#xD;
&#xD;
          -  Acceptable laboratory parameters&#xD;
&#xD;
          -  Adult (≥18 years old)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known brain metastasis&#xD;
&#xD;
          -  Any prior history of or suspected current autoimmune disorders (with the exception of&#xD;
             vitiligo, resolved childhood atopic dermatitis, prior Grave's disease)&#xD;
&#xD;
          -  Prior history of allogeneic bone marrow, stem-cell, or solid organ transplantation&#xD;
&#xD;
          -  Prior treatment with checkpoint inhibitors and other immunotherapy treatments,&#xD;
             including anti-LAG-3, anti-PD-1, anti-PD-L1 or anti-CTLA-4 antibodies, if less than 5&#xD;
             half lives before study drug administration&#xD;
&#xD;
          -  Prior history of Grade 3 or greater drug-related diarrhea/colitis during treatment&#xD;
             with checkpoint inhibitors or other immunotherapy treatments.&#xD;
&#xD;
          -  Treatment with any local or systemic anti-neoplastic therapy or any other&#xD;
             investigational agent in the 4 weeks prior to study drug administration&#xD;
&#xD;
          -  Require, at the time of study entry, treatment with steroids &gt; 10 mg/day of oral&#xD;
             prednisone (or equivalent), except topical use, steroid inhaler, nasal spray or&#xD;
             ophthalmic solution&#xD;
&#xD;
          -  History of clinically significant cardiovascular disease, gastrointestinal disorder,&#xD;
             or significant pulmonary compromise.&#xD;
&#xD;
          -  Second primary malignancy that has not been in remission for greater than 3 years,&#xD;
             with the exception of non-melanoma skin cancer, cervical carcinoma in situ,or squamous&#xD;
             intraepithelial lesion on PAP smear, localized prostate cancer (Gleason score &lt;6), or&#xD;
             resected melanoma in situ.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Yale University, Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center &amp; Research Institute, Inc</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Sidney Kimmel Comprehensive Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Carolina Biooncology Institute</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 22, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>February 4, 2022</last_update_submitted>
  <last_update_submitted_qc>February 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>colon cancer</keyword>
  <keyword>colorectal carcinoma</keyword>
  <keyword>stage IV colorectal cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_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/NCT02248805
org study id: CP-MGD007-01
nct id: NCT02248805
lead sponsor: 
has dmc: No
The primary goal of this Phase 1 study is to characterize the safety and tolerability of
      MGD007 and establish the maximum tolerated dose (MTD) and schedule of MGD007 administered to
      patients with metastatic colorectal carcinoma. Pharmacokinetics, pharmacodynamics, and the
      anti-tumor activity of MGD007 will also be assessed.
This is an open-label, multi-center, Phase 1 dose-escalation study to define a MTD, describe
      preliminarily safety, and to assess PK, immunogenicity, and potential anti-tumor activity of
      MGD007 in patients with relapsed or refractory metastatic colorectal cancer.

      In the initial phase of the study, two dose schedules will be assessed in dose escalation,
      once weekly and once every three weeks administration of single agent MGD007. Following the
      establishment of an MTD, additional patients will enroll in four separate dose expansion
      cohorts to further optimize the dose and schedule of MGD007 administration.

      In all segments of the study, patients who benefit from MGD007 treatment and continue to meet
      eligibility may continue treatment in Cycles 2 and beyond.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Characterize dose limiting toxicity and establish a maximum tolerated dose and schedule
time frame: Cycle 1 of a 6 week cycle
description: Safety is based on evaluation of adverse events (AEs) and serious adverse events (SAEs) from the time of study drug administration through the End of Study visit. The MTD will be defined separately for both the weekly and every three week schedules of MGD007 administration, and will be determined as the highest dose level at which the incidence of DLT is < 33% during the first cycle of MGD007 treatment.
measure: Characterize the PK and Immunogenicity of MGD007
time frame: Beginning of treatment through end of treatment, an expected duration of less than 12 months
description: Serum concentrations of MGD007 will be monitored. PK modeling will be performed and an appropriate model will be selected to describe the data.
measure: Describe any evidence of anti-tumor activity
time frame: Every 6 weeks until End of Study, an expected duration of less than 12 months
description: Obtain regular radiographic and clinical evaluations to assess treatment response.
arm group label: Does Escalation Arm A
arm group type: Experimental
description: MGD007 treatment once weekly
arm group label: Dose Escalation Arm B
arm group type: Experimental
description: MGD007 treatment once every 3 weeks
arm group label: Dose Expansion Arm C
arm group type: Experimental
description: MGD007 once every 3 weeks for K-ras wild-type and mutant metastatic CRC
arm group label: Dose Expansion Arms
arm group type: Experimental
description: MGD007 2, 3, 6, or 12 doses/cycle
intervention type: Drug
intervention name: MGD007
description: MGD007 is a gpA33 x CD3 bi-specific antibody-based molecular construct referred to as a DART molecule. MGD007 will be administered as a single agent.
arm group label: Does Escalation Arm A
arm group label: Dose Escalation Arm B
arm group label: Dose Expansion Arm C
arm group label: Dose Expansion Arms
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Colorectal Neoplasms