<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/NCT03832361</url>
  </required_header>
  <id_info>
    <org_study_id>2000023841</org_study_id>
    <nct_id>NCT03832361</nct_id>
  </id_info>
  <brief_title>Evaluation of Mirvetuximab Soravtansine (IMGN853) in Women With Folate Receptor-α Positive Endometrial Cancer</brief_title>
  <official_title>A Phase II Evaluation of the Safety and Efficacy of Mirvetuximab Soravtansine (IMGN853) in Women With Folate Receptor-α Positive Persistent or Recurrent Endometrial Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Alessandro Santin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>ImmunoGen, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</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>
      The purpose of this study is to evaluate the activity and safety profile of mirvetuximab&#xD;
      soravtansine (IMGN853) in patients with type II endometrial cancers that overexpress folate&#xD;
      receptor alpha (FRα).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will enroll patients with persistent or recurrent FRα-positive uterine serous&#xD;
      carcinoma (pure or mixed), Grade 3 endometrial adenocarcinoma, or carcinosarcoma with high&#xD;
      grade serous or Grade 3 endometrioid components. All patients must have measurable disease.&#xD;
      The primary objective of the study is to assess the activity of IMGN853 as measured by&#xD;
      objective response rate (ORR). The secondary objectives are to assess the duration of overall&#xD;
      survival (OS), progression-free survival (PFS) and durable disease control rate (DDCR), as&#xD;
      well as the safety profile of IMGN853 in endometrial carcinoma patients.&#xD;
      Exploratory/correlative objectives are to correlate ORR, PFS, and OS with the level of folate&#xD;
      receptor α expression and explore use of circulating tumor (ct) DNA as a biomarker for&#xD;
      disease response and compare its performance to cancer antigen 125 (CA-125). All enrolled&#xD;
      patients will receive IMGN853 at a dose of 6 mg/kg administered intravenously once every 3&#xD;
      weeks until unacceptable toxicity or progression of disease requiring discontinuation of&#xD;
      treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Anticipated">October 2028</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>Phase 2</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>Objective response rate (ORR)</measure>
    <time_frame>5 Years</time_frame>
    <description>Objective response rate (complete response and partial response rates) by RECIST 1.1 criteria of mirvetuximab soravtansine in patients with folate receptor α-positive persistent or recurrent endometrial cancer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of overall survival (OS)</measure>
    <time_frame>5 Years</time_frame>
    <description>Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of progression free survival (PFS)</measure>
    <time_frame>5 Years</time_frame>
    <description>Progression-free survival is defined as the duration of time from study entry to time of progression, death, or the date of last contact, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durable disease control rate (DDCR)</measure>
    <time_frame>5 Years</time_frame>
    <description>The percentage of patients who have achieved complete response, partial response, and stable disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety profile of mirvetuximab soravtansine (IMGN853) in endometrial cancer patients (adverse events as assessed by CTCAE v5.0)</measure>
    <time_frame>5 Years</time_frame>
    <description>Incidence of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Endometrial Cancer</condition>
  <arm_group>
    <arm_group_label>IMGN853</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>IMGN853 administered 6 mg/kg adjusted ideal body weight (AIBW) once every three weeks (Q3W)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IMGN853</intervention_name>
    <description>IMGN853 6 mg/kg intravenously every 3 weeks until disease progression</description>
    <arm_group_label>IMGN853</arm_group_label>
    <other_name>mirvetuximab soravtansine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Radiologically confirmed (ie, CT scan and/or MRI) persistent or recurrent endometrial&#xD;
             cancer&#xD;
&#xD;
          -  Patients must have one of the following pathologically documented, definitively&#xD;
             diagnosed tumor types: Uterine serous carcinoma (Pure or Mixed), Grade 2 or Grade 3&#xD;
             endometrial adenocarcinoma, Carcinosarcoma with high grade serous or Grade 2/3&#xD;
             endometrioid components, or clear cell carcinoma (Pure or Mixed).&#xD;
&#xD;
          -  Have measurable disease&#xD;
&#xD;
          -  FRα-positive tumor expression as defined in the protocol&#xD;
&#xD;
          -  Have at least one &quot;target lesion&quot; to be used to assess response as defined by RECIST&#xD;
             v1.1&#xD;
&#xD;
          -  Patients must have received prior treatment with ≤ 3 prior lines of therapy for&#xD;
             recurrent disease; hormonal agents are not considered a line of therapy; prior&#xD;
             treatment with folate receptor-targeting investigational agents is not allowed&#xD;
&#xD;
          -  Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Time from prior therapy: Systemic anti-neoplastic therapy: five half-lives or four&#xD;
             weeks, whichever is shorter; Radiotherapy: wide-field radiotherapy completed at least&#xD;
             four weeks, or focal radiation completed at least two weeks, prior to starting study&#xD;
             treatment&#xD;
&#xD;
          -  Patients must have resolution of toxic effect(s) of the most recent prior chemotherapy&#xD;
&#xD;
          -  Patients must have adequate hematologic, liver and kidney function as defined in the&#xD;
             protocol&#xD;
&#xD;
          -  Women of child bearing potential (WCBP), must agree to use effective contraceptive&#xD;
             methods during study treatment and for at least twelve weeks after the last dose of&#xD;
             IMGN853&#xD;
&#xD;
          -  WCBP must have a negative pregnancy test within 4 days prior to the first dose of&#xD;
             study treatment&#xD;
&#xD;
          -  At time of initial surgery, patient may have either been optimally or suboptimally&#xD;
             debulked&#xD;
&#xD;
          -  Have signed the informed consent form, and willing to adhere to the study visit&#xD;
             schedule and other protocol requirements&#xD;
&#xD;
          -  ≥ 18 years of age&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active or chronic corneal disorder&#xD;
&#xD;
          -  Serious concurrent illness or clinically-relevant active infection as defined in the&#xD;
             protocol&#xD;
&#xD;
          -  Clinically-significant cardiac disease such as recent myocardial infarction (≤ 6&#xD;
             months prior to day 1), unstable angina pectoris, uncontrolled congestive heart&#xD;
             failure, uncontrolled hypertension, prior history of hypertensive crisis or&#xD;
             hypertensive encephalopathy, uncontrolled cardiac arrhythmias, clinically-significant&#xD;
             vascular disease, severe aortic stenosis, clinically significant peripheral vascular&#xD;
             disease, or cardiac toxicity following prior chemotherapy&#xD;
&#xD;
          -  History of neurological conditions&#xD;
&#xD;
          -  History of hemorrhagic or ischemic stroke within the last 6 months&#xD;
&#xD;
          -  History of cirrhotic liver disease&#xD;
&#xD;
          -  Previous clinical diagnosis of non-infectious pneumonitis&#xD;
&#xD;
          -  Prior hypersensitivity to monoclonal antibodies&#xD;
&#xD;
          -  Women who are pregnant or breast feeding&#xD;
&#xD;
          -  Carcinomatous meningitis, untreated central nervous system (CNS) disease or&#xD;
             symptomatic CNS metastasis&#xD;
&#xD;
          -  History or evidence of thrombotic or hemorrhagic disorders within 6 months before&#xD;
             first study treatment&#xD;
&#xD;
          -  Required used of folate-containing supplements (e.g. folate deficiency)&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or required active treatment&#xD;
             within 3 years of first dose of study treatment&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alessandro D. Santin, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Yale University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Alessandro D. Santin, M.D.</last_name>
    <phone>203-737-4450</phone>
    <email>alessandro.santin@yale.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lisa Baker, R.N.</last_name>
    <phone>203-785-6398</phone>
    <email>lisa.baker@yale.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Smilow Cancer Hospital at Yale New Haven</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alessandro D Santin, M.D.</last_name>
      <phone>203-737-4450</phone>
      <email>alessandro.santin@yale.edu</email>
    </contact>
    <contact_backup>
      <last_name>Lisa Baker, R.N.</last_name>
      <phone>203-785-6398</phone>
      <email>lisa.baker@yale.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Alessandro Santin, M.D.</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>April 25, 2023</last_update_submitted>
  <last_update_submitted_qc>April 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Yale University</investigator_affiliation>
    <investigator_full_name>Alessandro Santin</investigator_full_name>
    <investigator_title>Professor of Obstetrics, Gynecology, and Reproductive Sciences</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endometrial Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mirvetuximab soravtansine</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/NCT03832361
org study id: 2000023841
nct id: NCT03832361
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the activity and safety profile of mirvetuximab
      soravtansine (IMGN853) in patients with type II endometrial cancers that overexpress folate
      receptor alpha (FRα).
This study will enroll patients with persistent or recurrent FRα-positive uterine serous
      carcinoma (pure or mixed), Grade 3 endometrial adenocarcinoma, or carcinosarcoma with high
      grade serous or Grade 3 endometrioid components. All patients must have measurable disease.
      The primary objective of the study is to assess the activity of IMGN853 as measured by
      objective response rate (ORR). The secondary objectives are to assess the duration of overall
      survival (OS), progression-free survival (PFS) and durable disease control rate (DDCR), as
      well as the safety profile of IMGN853 in endometrial carcinoma patients.
      Exploratory/correlative objectives are to correlate ORR, PFS, and OS with the level of folate
      receptor α expression and explore use of circulating tumor (ct) DNA as a biomarker for
      disease response and compare its performance to cancer antigen 125 (CA-125). All enrolled
      patients will receive IMGN853 at a dose of 6 mg/kg administered intravenously once every 3
      weeks until unacceptable toxicity or progression of disease requiring discontinuation of
      treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR)
time frame: 5 Years
description: Objective response rate (complete response and partial response rates) by RECIST 1.1 criteria of mirvetuximab soravtansine in patients with folate receptor α-positive persistent or recurrent endometrial cancer
measure: Duration of overall survival (OS)
time frame: 5 Years
description: Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.
measure: Duration of progression free survival (PFS)
time frame: 5 Years
description: Progression-free survival is defined as the duration of time from study entry to time of progression, death, or the date of last contact, whichever occurs first.
measure: Durable disease control rate (DDCR)
time frame: 5 Years
description: The percentage of patients who have achieved complete response, partial response, and stable disease.
measure: Safety profile of mirvetuximab soravtansine (IMGN853) in endometrial cancer patients (adverse events as assessed by CTCAE v5.0)
time frame: 5 Years
description: Incidence of treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
arm group label: IMGN853
arm group type: Experimental
description: IMGN853 administered 6 mg/kg adjusted ideal body weight (AIBW) once every three weeks (Q3W)
intervention type: Drug
intervention name: IMGN853
description: IMGN853 6 mg/kg intravenously every 3 weeks until disease progression
arm group label: IMGN853
other name: mirvetuximab soravtansine
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Alessandro D. Santin, M.D.
role: Principal Investigator
affiliation: Yale University
last name: Alessandro D. Santin, M.D.
phone: 203-737-4450
email: alessandro.santin@yale.edu
last name: Lisa Baker, R.N.
phone: 203-785-6398
email: lisa.baker@yale.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Yale University
investigator full name: Alessandro Santin
investigator title: Professor of Obstetrics, Gynecology, and Reproductive Sciences
mesh term: Endometrial Neoplasms
mesh term: Mirvetuximab soravtansine