<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/NCT02982941</url>
  </required_header>
  <id_info>
    <org_study_id>CP-MGA271-04</org_study_id>
    <nct_id>NCT02982941</nct_id>
  </id_info>
  <brief_title>Enoblituzumab (MGA271) in Children With B7-H3-expressing Solid Tumors</brief_title>
  <official_title>A Phase 1, Open-label, Dose Escalation Study of MGA271 in Pediatric Patients With B7-H3-Expressing Relapsed or Refractory Solid Tumors</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>
      This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to&#xD;
      characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor&#xD;
      activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses&#xD;
      (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or&#xD;
      refractory malignant solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to&#xD;
      characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor&#xD;
      activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses&#xD;
      (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or&#xD;
      refractory malignant solid tumors.&#xD;
&#xD;
      The study consists of a Dose Escalation Phase to determine the MTD (or MAD) of enoblituzumab&#xD;
      followed by a Cohort Expansion Phase to further define the safety and initial antitumor&#xD;
      activity of enoblituzumab. In the cohort expansion phase, 5 cohorts of 10 patients each will&#xD;
      be enrolled to further evaluate the safety and potential efficacy of enoblituzumab&#xD;
      administered at the MTD/MAD in patients with:1) neuroblastoma - measurable disease, 2)&#xD;
      neuroblastoma - non-measurable disease, 3) rhabdomyosarcoma, 4) osteosarcoma, and 5) Ewing's&#xD;
      sarcoma, Wilms' tumor, desmoplastic small round cell tumors, or malignant solid tumors of any&#xD;
      other histology that test positive for B7-H3.&#xD;
&#xD;
      All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid&#xD;
      Tumors (RECIST) and immune-related response criteria (irRC). Disease assessment in patients&#xD;
      with neuroblastoma will use neuroblastoma overall response criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2016</start_date>
  <completion_date type="Actual">May 22, 2019</completion_date>
  <primary_completion_date type="Actual">May 22, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of enoblituzumab.</measure>
    <time_frame>Time of first dose through end of treatment (up to 2 years)</time_frame>
    <description>Adverse events, SAEs, incidence of treatment-emergent AE</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration</measure>
    <time_frame>Time of first dose through end of treatment (up to 96 weeks)</time_frame>
    <description>PK of enoblituzumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants that develop anti-drug antibodies</measure>
    <time_frame>Time of first dose through end of treatment (up to 96 weeks)</time_frame>
    <description>Proportion of patients who develop anti-MGA271 antibodies, immunogenicity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Antitumor activity of enoblituzumab</measure>
    <time_frame>Time of first dose through end of treatment (up to 96 weeks)</time_frame>
    <description>Anti-tumor activity of enoblituzumab using conventional RECIST 1.1 and immune related RECIST criteria</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Neuroblastoma</condition>
  <condition>Rhabdomyosarcoma</condition>
  <condition>Osteosarcoma</condition>
  <condition>Ewing Sarcoma</condition>
  <condition>Wilms Tumor</condition>
  <condition>Desmoplastic Small Round Cell Tumor</condition>
  <arm_group>
    <arm_group_label>Dose Escalation &amp; Cohort Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>enoblituzumab administered IV weekly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Enoblituzumab</intervention_name>
    <description>enoblituzumab administered IV weekly for up to 96 weeks</description>
    <arm_group_label>Dose Escalation &amp; Cohort Expansion</arm_group_label>
    <other_name>MGA271</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        General Inclusion Criteria:&#xD;
&#xD;
          -  Age at treatment 1 to 35 years.&#xD;
&#xD;
          -  Relapsed or refractory malignant solid tumors of any histology for which no standard&#xD;
             curative therapy is available (escalation phase).&#xD;
&#xD;
          -  Histologically proven: neuroblastoma, rhabdomyosarcoma, osteosarcoma, Ewing's sarcoma/&#xD;
             primitive neuroectodermal tumor, Wilms tumor, desmoplastic small round cell tumor or&#xD;
             malignant solid tumors of any other histology that test positive for B7-H3 .&#xD;
&#xD;
          -  Must have malignant solid tumors that demonstrate B7-H3 expression at 2+ or greater&#xD;
             levels on the membranous surface of at least 10% of tumor cells or ≥ 25% of tumor&#xD;
             vasculature by IHC.&#xD;
&#xD;
          -  With the exception of patients with non-measurable neuroblastoma patients must have&#xD;
             measurable disease as per RECIST 1.1&#xD;
&#xD;
          -  Karnofsky (patients ≥ 16 years)/Lansky (patients &lt; 16 years) index ≥ 70.&#xD;
&#xD;
          -  Acceptable laboratory parameters and adequate organ reserve.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients are to be excluded from the study if they have any of the following:&#xD;
&#xD;
          -  Patients with a history of symptomatic central nervous system (CNS) unless they have&#xD;
             been treated and are asymptomatic.&#xD;
&#xD;
          -  Patients with any history of known or suspected autoimmune disease with the specific&#xD;
             exceptions of vitiligo, resolved childhood atopic dermatitis, psoriasis not requiring&#xD;
             systemic treatment within the past 2 years, and patients with a history of Grave's&#xD;
             disease that are now euthyroid clinically and by laboratory testing.&#xD;
&#xD;
          -  History of prior allogeneic bone marrow/stem-cell or solid organ transplantation.&#xD;
&#xD;
          -  Patients receiving autologous stem cell transplantation must wait 8 weeks before&#xD;
             initiation of study drug administration.&#xD;
&#xD;
          -  Treatment with systemic chemotherapy or investigational therapy within 4 weeks of&#xD;
             first study drug administration; other agents (e.g., biologics) within 2 weeks;&#xD;
             radiation within 2 weeks; patients receiving 131I-MIBG therapy must wait 6 weeks prior&#xD;
             to the initiation of study drug administration; corticosteroids (≥ 0.2 mg/kg/day&#xD;
             prednisone or equivalent) or other immune suppressive drugs within the 2 weeks prior&#xD;
             to the initiation of study drug administration.&#xD;
&#xD;
          -  History of clinically significant cardiovascular disease&#xD;
&#xD;
          -  Active viral, bacterial, or systemic fungal infection requiring parenteral treatment&#xD;
             within 7 days prior to the initiation of study drug.&#xD;
&#xD;
          -  Known positive testing for human immunodeficiency virus or history of acquired immune&#xD;
             deficiency syndrome.&#xD;
&#xD;
          -  Known history of hepatitis B or hepatitis C infection or known positive test for&#xD;
             hepatitis B surface antigen, hepatitis B core antigen, or hepatitis C polymerase chain&#xD;
             reaction.&#xD;
&#xD;
          -  Second primary invasive malignancy that has not been in remission for greater than 2&#xD;
             years.&#xD;
&#xD;
          -  History of severe trauma or major surgery within 4 weeks prior to the initiation of&#xD;
             study drug administration.&#xD;
&#xD;
          -  Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient&#xD;
             contained in the drug formulation for enoblituzumab&#xD;
&#xD;
          -  Patients in Canada may not have a history or evidence of latent or active tuberculosis&#xD;
             infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>1 Year</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chief Medical Officer</last_name>
    <role>Study Director</role>
    <affiliation>MacroGenics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Lucile Packard Children's Hospital, Stanford</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Institute, Center for Cancer Research</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Children's Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Children's</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin, American Family Children's Hospital</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</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>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</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>Neuroblastoma</keyword>
  <keyword>Rhabdomyosarcoma</keyword>
  <keyword>Osteosarcoma</keyword>
  <keyword>Ewing Sarcoma</keyword>
  <keyword>Wilms Tumor</keyword>
  <keyword>Desmoplastic Small Round Cell Tumor</keyword>
  <keyword>pediatric</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Neuroblastoma</mesh_term>
    <mesh_term>Osteosarcoma</mesh_term>
    <mesh_term>Rhabdomyosarcoma</mesh_term>
    <mesh_term>Sarcoma, Ewing</mesh_term>
    <mesh_term>Wilms Tumor</mesh_term>
    <mesh_term>Desmoplastic Small Round Cell Tumor</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02982941
org study id: CP-MGA271-04
nct id: NCT02982941
lead sponsor: 
has dmc: No
This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to
      characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor
      activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses
      (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or
      refractory malignant solid tumors.
This study is a Phase 1, open-label, dose escalation and cohort expansion trial designed to
      characterize the safety, tolerability, PK, PD, immunogenicity and preliminary antitumor
      activity of enoblituzumab administered IV on a weekly schedule for up to 96 doses
      (approximately 2 years) in children and young adults with B7-H3-expressing relapsed or
      refractory malignant solid tumors.

      The study consists of a Dose Escalation Phase to determine the MTD (or MAD) of enoblituzumab
      followed by a Cohort Expansion Phase to further define the safety and initial antitumor
      activity of enoblituzumab. In the cohort expansion phase, 5 cohorts of 10 patients each will
      be enrolled to further evaluate the safety and potential efficacy of enoblituzumab
      administered at the MTD/MAD in patients with:1) neuroblastoma - measurable disease, 2)
      neuroblastoma - non-measurable disease, 3) rhabdomyosarcoma, 4) osteosarcoma, and 5) Ewing's
      sarcoma, Wilms' tumor, desmoplastic small round cell tumors, or malignant solid tumors of any
      other histology that test positive for B7-H3.

      All tumor evaluations will be carried out by both Response Evaluation Criteria in Solid
      Tumors (RECIST) and immune-related response criteria (irRC). Disease assessment in patients
      with neuroblastoma will use neuroblastoma overall response criteria.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of enoblituzumab.
time frame: Time of first dose through end of treatment (up to 2 years)
description: Adverse events, SAEs, incidence of treatment-emergent AE
measure: Peak plasma concentration
time frame: Time of first dose through end of treatment (up to 96 weeks)
description: PK of enoblituzumab
measure: Number of participants that develop anti-drug antibodies
time frame: Time of first dose through end of treatment (up to 96 weeks)
description: Proportion of patients who develop anti-MGA271 antibodies, immunogenicity
measure: Antitumor activity of enoblituzumab
time frame: Time of first dose through end of treatment (up to 96 weeks)
description: Anti-tumor activity of enoblituzumab using conventional RECIST 1.1 and immune related RECIST criteria
arm group label: Dose Escalation & Cohort Expansion
arm group type: Experimental
description: enoblituzumab administered IV weekly
intervention type: Drug
intervention name: Enoblituzumab
description: enoblituzumab administered IV weekly for up to 96 weeks
arm group label: Dose Escalation & Cohort Expansion
other name: MGA271
criteria: 
gender: All
minimum age: 1 Year
maximum age: 35 Years
healthy volunteers: No
last name: Chief Medical Officer
role: Study Director
affiliation: MacroGenics
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Sarcoma
mesh term: Neuroblastoma
mesh term: Osteosarcoma
mesh term: Rhabdomyosarcoma
mesh term: Sarcoma, Ewing
mesh term: Wilms Tumor
mesh term: Desmoplastic Small Round Cell Tumor
sharing ipd: No