<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/NCT03266692</url>
  </required_header>
  <id_info>
    <org_study_id>ATTCK-17-01</org_study_id>
    <nct_id>NCT03266692</nct_id>
  </id_info>
  <brief_title>Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma</brief_title>
  <official_title>A Phase 1 Study of ACTR087, an Autologous T Cell Product, in Combination With SEA-BCMA, a Monoclonal Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cogent Biosciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Cogent Biosciences, 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 phase 1, multi-center, single-arm, open-label study evaluating the safety,&#xD;
      tolerability, and anti-myeloma activity of ACTR087 (an autologous T cell product) in&#xD;
      combination with SEA-BCMA (a monoclonal antibody) in subjects with relapsed or refractory&#xD;
      Multiple Myeloma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Business reasons&#xD;
  </why_stopped>
  <start_date type="Actual">February 22, 2018</start_date>
  <completion_date type="Actual">October 1, 2019</completion_date>
  <primary_completion_date type="Actual">October 1, 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 ACTR087 in combination with SEA-BCMA</measure>
    <time_frame>28 days</time_frame>
    <description>Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determination of recommended Phase 2 dosing regimen</measure>
    <time_frame>52 weeks</time_frame>
    <description>Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs)</measure>
    <time_frame>21 days</time_frame>
    <description>Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-myeloma activity as measured by overall response rate (per IMWG response criteria)</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-myeloma activity as measured by duration of response</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-myeloma activity as measured by progression-free survival</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-myeloma activity as measured by overall survival</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of ACTR087 phenotype and function as measured by flow cytometry</measure>
    <time_frame>52 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration</measure>
    <time_frame>52 weeks</time_frame>
    <description>Levels of inflammatory markers, cytokines/chemokines</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SEA-BCMA PK</measure>
    <time_frame>52 weeks</time_frame>
    <description>SEA-BCMA plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration</measure>
    <time_frame>52 weeks</time_frame>
    <description>Incidence of ADAs to SEA-BCMA</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Multiple Myeloma</condition>
  <condition>Multiple Myeloma in Relapse</condition>
  <condition>Refractory Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>ACTR087 in combination with SEA-BCMA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ACTR087</intervention_name>
    <description>Autologous T cell product</description>
    <arm_group_label>ACTR087 in combination with SEA-BCMA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>SEA-BCMA</intervention_name>
    <description>B-cell maturation antigen (BCMA)-directed antibody</description>
    <arm_group_label>ACTR087 in combination with SEA-BCMA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed written informed consent obtained prior to study procedures&#xD;
&#xD;
          -  Histologically- or cytologically-confirmed relapsed or refractory multiple myeloma&#xD;
             (MM) with measurable disease&#xD;
&#xD;
          -  Must have received at least 3 prior lines of therapy to include treatment with a&#xD;
             proteasome inhibitor (eg, bortezomib, carfilzomib, or ixazomib) and an&#xD;
             immunomodulatory agent (eg, lenalidomide, pomalidomide) unless double-refractory to&#xD;
             both; and a hematopoietic stem cell transplant (HSCT), for those subjects considered&#xD;
             HSCT-eligible.&#xD;
&#xD;
          -  Quantitative serum IgG levels for subjects with IgG MM must not exceed the&#xD;
             institutional upper limit of normal (ULN)&#xD;
&#xD;
          -  ECOG 0 or 1&#xD;
&#xD;
          -  Life expectancy of at least 6 months&#xD;
&#xD;
          -  Absolute neutrophil (ANC) count greater than 1000/ µL&#xD;
&#xD;
          -  Platelet count greater than 50,000/µL&#xD;
&#xD;
          -  Estimated GFR &gt;30mL/min/1.73m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known active central nervous system (CNS) involvement by MM&#xD;
&#xD;
          -  Systemic rheumatic or autoimmune diseases or acute or chronic infections&#xD;
&#xD;
          -  Uncontrolled thromboembolic events or recent severe hemorrhage&#xD;
&#xD;
          -  Subjects who are currently using more than 5mg/day of prednisone (or an equivalent&#xD;
             glucocorticoid exceeding physiologic replacement levels)&#xD;
&#xD;
          -  Prior treatment as follows:&#xD;
&#xD;
               -  T cell-directed antibody therapy (eg. Alemtuzumab, anti-thymocyte globulin)&#xD;
                  within 6 months of enrollment&#xD;
&#xD;
               -  Any prior myeloma-directed therapy including cytotoxic chemotherapy, biologic&#xD;
                  therapy, or radiotherapy within 2 weeks of enrollment&#xD;
&#xD;
               -  Any mAb or other protein therapeutic containing Fc-domains within 4 weeks of&#xD;
                  enrollment&#xD;
&#xD;
               -  Experimental agents within 3 half-lives prior to enrollment, unless progression&#xD;
                  is documented on therapy&#xD;
&#xD;
               -  Prior BCMA-directed investigational agents at any time&#xD;
&#xD;
               -  Prior cell or gene therapy, excluding transfers of genetically unmodified&#xD;
                  autologous cells (eg. Hematopoietic stem cell transplantation), at any time; or&#xD;
                  prior allogeneic HSCT at any time&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jessica Sachs, MD</last_name>
    <role>Study Director</role>
    <affiliation>Cogent Biosciences, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana Blood and Marrow Transplantation</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46327</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohio State University Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor Scott &amp; White</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>August 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>March 27, 2020</last_update_submitted>
  <last_update_submitted_qc>March 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>BCMA</keyword>
  <keyword>SEA-BCMA</keyword>
  <keyword>B Cell Maturation Antigen</keyword>
  <keyword>ACTR</keyword>
  <keyword>ACTR087</keyword>
  <keyword>T cell</keyword>
  <keyword>T cell product</keyword>
  <keyword>relapsed</keyword>
  <keyword>refractory</keyword>
  <keyword>multiple myeloma</keyword>
  <keyword>adoptive T cells</keyword>
  <keyword>autologous</keyword>
  <keyword>gene therapy</keyword>
  <keyword>cell therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</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/NCT03266692
org study id: ATTCK-17-01
nct id: NCT03266692
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 1, multi-center, single-arm, open-label study evaluating the safety,
      tolerability, and anti-myeloma activity of ACTR087 (an autologous T cell product) in
      combination with SEA-BCMA (a monoclonal antibody) in subjects with relapsed or refractory
      Multiple Myeloma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety and tolerability of ACTR087 in combination with SEA-BCMA
time frame: 28 days
description: Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values
measure: Determination of recommended Phase 2 dosing regimen
time frame: 52 weeks
description: Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values
measure: Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs)
time frame: 21 days
description: Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values
measure: Anti-myeloma activity as measured by overall response rate (per IMWG response criteria)
time frame: 52 weeks
measure: Anti-myeloma activity as measured by duration of response
time frame: 52 weeks
measure: Anti-myeloma activity as measured by progression-free survival
time frame: 52 weeks
measure: Anti-myeloma activity as measured by overall survival
time frame: 52 weeks
measure: Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR
time frame: 52 weeks
measure: Assessment of ACTR087 phenotype and function as measured by flow cytometry
time frame: 52 weeks
measure: Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration
time frame: 52 weeks
description: Levels of inflammatory markers, cytokines/chemokines
measure: SEA-BCMA PK
time frame: 52 weeks
description: SEA-BCMA plasma concentration
measure: Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration
time frame: 52 weeks
description: Incidence of ADAs to SEA-BCMA
arm group label: ACTR087 in combination with SEA-BCMA
arm group type: Experimental
intervention type: Biological
intervention name: ACTR087
description: Autologous T cell product
arm group label: ACTR087 in combination with SEA-BCMA
intervention type: Biological
intervention name: SEA-BCMA
description: B-cell maturation antigen (BCMA)-directed antibody
arm group label: ACTR087 in combination with SEA-BCMA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jessica Sachs, MD
role: Study Director
affiliation: Cogent Biosciences, Inc.
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell