<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/NCT04480502</url>
  </required_header>
  <id_info>
    <org_study_id>KN035SAR201</org_study_id>
    <nct_id>NCT04480502</nct_id>
  </id_info>
  <brief_title>ENVASARC: Envafolimab And Envafolimab With Ipilimumab In Patients With Undifferentiated Pleomorphic Sarcoma Or Myxofibrosarcoma</brief_title>
  <acronym>ENVASARC</acronym>
  <official_title>ENVASARC: A Pivotal Trial Of Envafolimab, And Envafolimab In Combination With Ipilimumab, In Patients With Advanced Or Metastatic Undifferentiated Pleomorphic Sarcoma Or Myxofibrosarcoma Who Have Progressed On Prior Chemotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tracon Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tracon Pharmaceuticals Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a multicenter open-label, randomized, non-comparative, parallel cohort pivotal study&#xD;
      of treatment with envafolimab (cohort A and C) or envafolimab combined with ipilimumab&#xD;
      (cohort B and D) in patients with locally advanced, unresectable or metastatic&#xD;
      undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma (MFS) who have progressed on one&#xD;
      or two lines of chemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter open-label, randomized, non-comparative, parallel cohort pivotal study&#xD;
      of treatment with envafolimab (cohort A and C) or envafolimab combined with ipilimumab&#xD;
      (cohort B and D) in patients with locally advanced, unresectable or metastatic UPS/MFS who&#xD;
      have progressed on one or two lines of chemotherapy. Patients were previously assigned at&#xD;
      random into one of two cohorts: cohort A of 80 patients who received single agent envafolimab&#xD;
      (300 mg every 3 weeks by subcutaneous (SC) injection) or cohort B of 80 patients who received&#xD;
      envafolimab (300 mg every 3 weeks by SC injection) in combination with ipilimumab (1 mg/kg&#xD;
      every 3 weeks intravenously for four doses). Following amendment #3, patients will be&#xD;
      assigned at random into one of two cohorts: cohort C of 80 patients who will receive single&#xD;
      agent envafolimab (600 mg every 3 weeks by subcutaneous (SC) injection) or cohort D of 80&#xD;
      patients who will receive envafolimab 600 mg every 3 weeks by SC injection) in combination&#xD;
      with ipilimumab (1 mg/kg every 3 weeks intravenously for four doses).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 9, 2020</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">June 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective response rate (ORR) by RECIST 1.1 assessed by blinded independent central review</measure>
    <time_frame>40 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DR) assessed by blinded independent central review</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR) assessed by blinded independent central review</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) assessed by blinded independent central review</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterize envafolimab pharmacokinetics (PK) in patients receiving envafolimab as a single agent and in combination with ipilimumab</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterize ipilimumab PK in patients given ipilimumab with envafolimab</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR) by investigator assessment</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) by investigator assessment</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Characterize the immunogenicity of envafolimab and ipilimumab</measure>
    <time_frame>40 months</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">230</enrollment>
  <condition>Undifferentiated Pleomorphic Sarcoma</condition>
  <condition>Myxofibrosarcoma</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with 300 mg of single agent envafolimab every three weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with envafolimab in combination with ipilimumab. Envafolimab will be given at 300 mg every three weeks. Ipilimumab will be given at 1 mg/kg every three weeks for a total of four doses.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with 600 mg of single agent envafolimab every three weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients treated with envafolimab in combination with ipilimumab. Envafolimab will be given at 600 mg every three weeks. Ipilimumab will be given at 1 mg/kg every three weeks for a total of four doses.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Envafolimab</intervention_name>
    <description>PD-L1 single domain antibody for subcutaneous injection.</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
    <other_name>KN035</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>CTLA-4 monoclonal antibody</description>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
    <other_name>Yervoy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed locally advanced or metastatic undifferentiated pleomorphic&#xD;
             sarcoma (UPS) or grade ≥ 2 myxofibrosarcoma (MFS)&#xD;
&#xD;
          -  Documented progression following systemic chemotherapy&#xD;
&#xD;
          -  At least one measurable lesion&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status of 0 or 1&#xD;
&#xD;
          -  Adequate hematologic and organ function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  More than two prior lines of chemotherapy for UPS/MFS&#xD;
&#xD;
          -  Prior immune checkpoint inhibitor or immunomodulatory therapy&#xD;
&#xD;
          -  Active autoimmune disease that has required systemic treatment&#xD;
&#xD;
          -  Major surgery within 4 weeks of dosing of investigational agent&#xD;
&#xD;
          -  Active additional malignancy&#xD;
&#xD;
          -  Pericardial effusion, pleural effusion, or ascites&#xD;
&#xD;
          -  Central nervous system metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  Active hepatitis or cirrhosis&#xD;
&#xD;
          -  Interstitial lung disease&#xD;
&#xD;
          -  Unwilling to apply highly effective contraception during the study&#xD;
&#xD;
          -  Other concurrent severe and/or uncontrolled medical conditions that would, in the&#xD;
             investigator's judgment, contraindicate patient participation in the clinical study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Charles Theuer, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Tracon Pharmaceuticals Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Charles Theuer, MD, PhD</last_name>
    <phone>858-550-0780</phone>
    <email>clinicaltrials@traconpharma.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Arizona</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85721</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Sarcoma Oncology Research Center</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90403</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Colorado</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic, Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>H. Lee Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <zip>60208</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21218</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </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>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Michigan</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55901</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Washington University in St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63130</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Columbia University</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10027</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27708</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University Hospitals</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>89106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19106</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University (Sidney Kimmel Cancer Center)</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15260</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37235</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23284</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Wauwatosa</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Royal Marsden</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <last_update_submitted>April 10, 2023</last_update_submitted>
  <last_update_submitted_qc>April 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sarcoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sarcoma</mesh_term>
    <mesh_term>Histiocytoma, Malignant Fibrous</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ipilimumab</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/NCT04480502
org study id: KN035SAR201
nct id: NCT04480502
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a multicenter open-label, randomized, non-comparative, parallel cohort pivotal study
      of treatment with envafolimab (cohort A and C) or envafolimab combined with ipilimumab
      (cohort B and D) in patients with locally advanced, unresectable or metastatic
      undifferentiated pleomorphic sarcoma (UPS)/myxofibrosarcoma (MFS) who have progressed on one
      or two lines of chemotherapy.
This is a multicenter open-label, randomized, non-comparative, parallel cohort pivotal study
      of treatment with envafolimab (cohort A and C) or envafolimab combined with ipilimumab
      (cohort B and D) in patients with locally advanced, unresectable or metastatic UPS/MFS who
      have progressed on one or two lines of chemotherapy. Patients were previously assigned at
      random into one of two cohorts: cohort A of 80 patients who received single agent envafolimab
      (300 mg every 3 weeks by subcutaneous (SC) injection) or cohort B of 80 patients who received
      envafolimab (300 mg every 3 weeks by SC injection) in combination with ipilimumab (1 mg/kg
      every 3 weeks intravenously for four doses). Following amendment #3, patients will be
      assigned at random into one of two cohorts: cohort C of 80 patients who will receive single
      agent envafolimab (600 mg every 3 weeks by subcutaneous (SC) injection) or cohort D of 80
      patients who will receive envafolimab 600 mg every 3 weeks by SC injection) in combination
      with ipilimumab (1 mg/kg every 3 weeks intravenously for four doses).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR) by RECIST 1.1 assessed by blinded independent central review
time frame: 40 months
measure: Duration of response (DR) assessed by blinded independent central review
time frame: 40 months
measure: Disease control rate (DCR) assessed by blinded independent central review
time frame: 40 months
measure: Progression free survival (PFS) assessed by blinded independent central review
time frame: 40 months
measure: Overall survival (OS)
time frame: 40 months
measure: Characterize envafolimab pharmacokinetics (PK) in patients receiving envafolimab as a single agent and in combination with ipilimumab
time frame: 40 months
measure: Characterize ipilimumab PK in patients given ipilimumab with envafolimab
time frame: 40 months
measure: Objective response rate (ORR) by investigator assessment
time frame: 40 months
measure: Progression free survival (PFS) by investigator assessment
time frame: 40 months
measure: Characterize the immunogenicity of envafolimab and ipilimumab
time frame: 40 months
arm group label: Cohort A
arm group type: Experimental
description: Patients treated with 300 mg of single agent envafolimab every three weeks
arm group label: Cohort B
arm group type: Experimental
description: Patients treated with envafolimab in combination with ipilimumab. Envafolimab will be given at 300 mg every three weeks. Ipilimumab will be given at 1 mg/kg every three weeks for a total of four doses.
arm group label: Cohort C
arm group type: Experimental
description: Patients treated with 600 mg of single agent envafolimab every three weeks
arm group label: Cohort D
arm group type: Experimental
description: Patients treated with envafolimab in combination with ipilimumab. Envafolimab will be given at 600 mg every three weeks. Ipilimumab will be given at 1 mg/kg every three weeks for a total of four doses.
intervention type: Biological
intervention name: Envafolimab
description: PD-L1 single domain antibody for subcutaneous injection.
arm group label: Cohort A
arm group label: Cohort B
arm group label: Cohort C
arm group label: Cohort D
other name: KN035
intervention type: Drug
intervention name: Ipilimumab
description: CTLA-4 monoclonal antibody
arm group label: Cohort B
arm group label: Cohort D
other name: Yervoy
criteria: 
gender: All
minimum age: 12 Years
maximum age: N/A
healthy volunteers: No
last name: Charles Theuer, MD, PhD
role: Study Director
affiliation: Tracon Pharmaceuticals Inc.
last name: Charles Theuer, MD, PhD
phone: 858-550-0780
email: clinicaltrials@traconpharma.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Sarcoma
mesh term: Histiocytoma, Malignant Fibrous
mesh term: Ipilimumab