<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/NCT02984683</url>
  </required_header>
  <id_info>
    <org_study_id>ACT14884</org_study_id>
    <secondary_id>2016-001962-27</secondary_id>
    <secondary_id>U1111-1182-7044</secondary_id>
    <nct_id>NCT02984683</nct_id>
  </id_info>
  <brief_title>Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer</brief_title>
  <official_title>Open-label Phase 2 Study Evaluating Efficacy and Safety of SAR566658 Treatment in Patients With CA6 Positive Metastatic Triple Negative Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sanofi</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sanofi</source>
  <oversight_info>
    <has_dmc>No</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>
      Primary Objective:&#xD;
&#xD;
      To evaluate the tumor Objective Response Rate (ORR), according to the Response Evaluation&#xD;
      Criteria in Solid Tumors (RECIST 1.1) of SAR566658 in participants with anti-carbonic&#xD;
      anhydrase 6 (CA6)-positive metastatic triple negative breast cancer (TNBC). Part 1: To select&#xD;
      the SAR566658 dose based on ORR and safety of 2 dose levels of SAR566658. Part 2: Part 2a: To&#xD;
      demonstrate the activity of SAR566658 based on ORR in participants overexpressing CA6&#xD;
      (membrane intensity of 2+, 3+ in greater than or equal to (&gt;=) 30% of tumor cells) treated at&#xD;
      the selected dose in an expanded cohort, in addition to the participants treated in Part 1. -&#xD;
      Part 2b: To assess the efficacy in participants with metastatic TNBC and mild CA6 expression.&#xD;
&#xD;
      Secondary Objectives:&#xD;
&#xD;
      To assess:&#xD;
&#xD;
        -  Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS),&#xD;
           and Time To Progression (TTP).&#xD;
&#xD;
        -  The impact of ocular primary prophylaxis on the incidence of keratopathies.&#xD;
&#xD;
        -  The potential immunogenicity of SAR566658.&#xD;
&#xD;
        -  To evaluate the global safety profile.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The duration of the study for 1 participant included a screening period of up to 21 days&#xD;
      prior to first study drug administration, 3-week treatment cycle(s) (until 30 days after last&#xD;
      SAR566658 administration), and a follow-up period. Each participant was treated until&#xD;
      radiological disease progression, unacceptable toxicity, or participant's refusal of further&#xD;
      study treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study discontinued considering the limited clinical benefit combined with a higher than&#xD;
    expected rate of known non-serious ophthalmological event.&#xD;
  </why_stopped>
  <start_date type="Actual">March 23, 2017</start_date>
  <completion_date type="Actual">September 7, 2018</completion_date>
  <primary_completion_date type="Actual">September 7, 2018</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>Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings</measure>
    <time_frame>Up to Cycle 2 (each cycle of 21 days)</time_frame>
    <description>Predefined safety criteria was defined as occurrence of following IMP-related treatment-emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade greater than or equal to (&gt;=) 3 TEAE from the System Organ Class (SOC) of eye disorders, Grade &gt;=3 peripheral neuropathy (Preferred Term), Grade &gt;=4 TEAE. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Objective Response</measure>
    <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
    <description>Objective Response in participants was defined as the participants with complete response (CR) and partial response (PR) as best response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease Control</measure>
    <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
    <description>Disease control in participants was defined as the participants with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
    <description>DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first radiological documentation of tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
    <description>PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Tumor Progression (TTP)</measure>
    <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
    <description>TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumor progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)</measure>
    <time_frame>Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)</time_frame>
    <description>AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Keratopathies (Corneal Toxicity)</measure>
    <time_frame>Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)</time_frame>
    <description>Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All participants received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Positive Anti-SAR566658 Antibodies Response</measure>
    <time_frame>Up to 3 treatment cycles, each cycle 21 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>SAR566658 90 mg/m^2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SAR566658 90 milligram per square meter (mg/m^2) as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAR566658 120 mg/m^2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAR566658 (ACT14884)</intervention_name>
    <description>Pharmaceutical form:Solution Route of administration: Intravenous</description>
    <arm_group_label>SAR566658 120 mg/m^2</arm_group_label>
    <arm_group_label>SAR566658 90 mg/m^2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria :&#xD;
&#xD;
          -  Measurable Metastatic TNBC.&#xD;
&#xD;
          -  Participants with CA6-positive disease.&#xD;
&#xD;
          -  Participants received at least 1 prior chemotherapy regimen but no more than 3 for&#xD;
             advanced/metastatic disease.&#xD;
&#xD;
          -  Prior anticancer therapy must have contained anthracycline (eg, doxorubicin), if not&#xD;
             contraindicated, and a taxane (eg, docetaxel, paclitaxel) in an adjuvant/neo-adjuvant&#xD;
             or metastatic setting.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status &gt;=2.&#xD;
&#xD;
          -  Participant less than 18 years old.&#xD;
&#xD;
          -  Pregnant or breast-feeding women.&#xD;
&#xD;
          -  Participants with reproductive potential who do not agree to use accepted and&#xD;
             effective method of contraception during the study treatment period and for 6 months&#xD;
             following discontinuation of study drug.&#xD;
&#xD;
          -  Wash out period of less than 3 weeks or 5 half-lives from previous antitumor&#xD;
             chemotherapy, immunotherapy, or any investigational treatment.&#xD;
&#xD;
          -  History of brain metastasis (other than totally resected or previously irradiated and&#xD;
             nonprogressive/relapsed), spinal cord compression or carcinomatous meningitis, or new&#xD;
             evidence of brain leptomeningeal disease.&#xD;
&#xD;
          -  Prior treatment with eribulin as last prior therapy or prior maytansinoid treatments&#xD;
             (DM1 or DM4 antibody-drug conjugates [ADCs]).&#xD;
&#xD;
          -  Known intolerance to infused protein products including other monoclonal antibodies&#xD;
             and ADCs.&#xD;
&#xD;
          -  Poor bone marrow reserve and/or poor organ function.&#xD;
&#xD;
          -  Symptomatic peripheral neuropathy Grade &gt;=2.&#xD;
&#xD;
          -  Previous history of chronic corneal diseases (even if asymptomatic) or unresolved&#xD;
             acute nonrecurrent corneal conditions.&#xD;
&#xD;
          -  Participants wearing contact lenses who are not willing to stop wearing them for the&#xD;
             duration of the study.&#xD;
&#xD;
          -  Medical conditions requiring concomitant administration of strong Cytochrome P450 3A4&#xD;
             (CYP3A4) inhibitors, unless it could be discontinued at least 2 weeks before 1st&#xD;
             administration of SAR566658.&#xD;
&#xD;
          -  Contraindications to the use of ophthalmic vasoconstrictor and/or corticosteroid.&#xD;
&#xD;
        The above information was not intended to contain all considerations relevant to a&#xD;
        participant's potential participation in a clinical trial.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Sciences &amp; Operations</last_name>
    <role>Study Director</role>
    <affiliation>Sanofi</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Investigational Site Number 0560001</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 2030002</name>
      <address>
        <city>Praha 2</city>
        <zip>12808</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 3800003</name>
      <address>
        <city>Genova</city>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 3800001</name>
      <address>
        <city>Milano</city>
        <zip>20132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 3800004</name>
      <address>
        <city>Roma</city>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 5280001</name>
      <address>
        <city>Maastricht</city>
        <zip>6229 HX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 5280002</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 GD</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 7240002</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 7240005</name>
      <address>
        <city>Lleida</city>
        <zip>25198</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 7240001</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 7240006</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 7240003</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigational Site Number 7240004</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Czechia</country>
    <country>Italy</country>
    <country>Netherlands</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>December 4, 2016</study_first_submitted>
  <study_first_submitted_qc>December 4, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 7, 2016</study_first_posted>
  <results_first_submitted>August 11, 2021</results_first_submitted>
  <results_first_submitted_qc>August 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">September 8, 2021</results_first_posted>
  <disposition_first_submitted>August 12, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>August 12, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">August 16, 2019</disposition_first_posted>
  <last_update_submitted>August 11, 2021</last_update_submitted>
  <last_update_submitted_qc>August 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 15, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT02984683/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 29, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT02984683/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 13 sites in 5 countries from 23 March 2017 to 07 September 2018.</recruitment_details>
      <pre_assignment_details>A total of 23 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled in the study and included in Part 1. The study was prematurely terminated due to safety reasons, hence Part 2 was not conducted and no analysis was performed.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>SAR566658 90 mg/m^2</title>
          <description>Participants received SAR566658 90 milligram per square meter (mg/m^2) as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
        </group>
        <group group_id="P2">
          <title>SAR566658 120 mg/m^2</title>
          <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Analysis was performed on randomized population.</population>
      <group_list>
        <group group_id="B1">
          <title>SAR566658 90 mg/m^2</title>
          <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
        </group>
        <group group_id="B2">
          <title>SAR566658 120 mg/m^2</title>
          <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="11"/>
            <count group_id="B2" value="12"/>
            <count group_id="B3" value="23"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.73" spread="11.23"/>
                    <measurement group_id="B2" value="50.33" spread="15.30"/>
                    <measurement group_id="B3" value="53.39" spread="13.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings</title>
        <description>Predefined safety criteria was defined as occurrence of following IMP-related treatment-emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade greater than or equal to (&gt;=) 3 TEAE from the System Organ Class (SOC) of eye disorders, Grade &gt;=3 peripheral neuropathy (Preferred Term), Grade &gt;=4 TEAE. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.</description>
        <time_frame>Up to Cycle 2 (each cycle of 21 days)</time_frame>
        <population>Analysis was performed on participants evaluable for predefined safety criteria population which included participants treated in the study and had completed 2 cycles, or who experienced predefined safety criteria.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings</title>
          <description>Predefined safety criteria was defined as occurrence of following IMP-related treatment-emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade greater than or equal to (&gt;=) 3 TEAE from the System Organ Class (SOC) of eye disorders, Grade &gt;=3 peripheral neuropathy (Preferred Term), Grade &gt;=4 TEAE. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.</description>
          <population>Analysis was performed on participants evaluable for predefined safety criteria population which included participants treated in the study and had completed 2 cycles, or who experienced predefined safety criteria.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade&gt;=3 related TEAE from SOC Eye disorders</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade&gt;=3 related peripheral neuropathy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade&gt;=4 related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Objective Response</title>
        <description>Objective Response in participants was defined as the participants with complete response (CR) and partial response (PR) as best response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
        <population>Analysis was performed on all-treated population which included participants who actually received at least 1 dose or any partial dose of SAR566658.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Objective Response</title>
          <description>Objective Response in participants was defined as the participants with complete response (CR) and partial response (PR) as best response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Analysis was performed on all-treated population which included participants who actually received at least 1 dose or any partial dose of SAR566658.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>80% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1" lower_limit="1.0" upper_limit="31.0"/>
                    <measurement group_id="O2" value="8.3" lower_limit="0.9" upper_limit="28.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Disease Control</title>
        <description>Disease control in participants was defined as the participants with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.</description>
        <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
        <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Disease Control</title>
          <description>Disease control in participants was defined as the participants with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.</description>
          <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first radiological documentation of tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.</description>
        <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
        <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first radiological documentation of tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.</description>
          <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions.</description>
        <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
        <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions.</description>
          <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Tumor Progression (TTP)</title>
        <description>TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumor progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.</description>
        <time_frame>Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)</time_frame>
        <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Tumor Progression (TTP)</title>
          <description>TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumor progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.</description>
          <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)</title>
        <description>AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.</description>
        <time_frame>Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)</time_frame>
        <population>Analysis was performed on all treated population.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)</title>
          <description>AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.</description>
          <population>Analysis was performed on all treated population.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any treatment emergent SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any TEAE leading to treatment discontinuation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Keratopathies (Corneal Toxicity)</title>
        <description>Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All participants received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration.</description>
        <time_frame>Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)</time_frame>
        <population>Analysis was performed on all treated population.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Keratopathies (Corneal Toxicity)</title>
          <description>Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All participants received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration.</description>
          <population>Analysis was performed on all treated population.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Positive Anti-SAR566658 Antibodies Response</title>
        <time_frame>Up to 3 treatment cycles, each cycle 21 days</time_frame>
        <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
        <group_list>
          <group group_id="O1">
            <title>SAR566658 90 mg/m^2</title>
            <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
          <group group_id="O2">
            <title>SAR566658 120 mg/m^2</title>
            <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Positive Anti-SAR566658 Antibodies Response</title>
          <population>Data for this outcome measure was not collected and analyzed due to early termination of the study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event (AE) data was collected from the baseline up to 3 treatment cycles, each cycle 21 days.</time_frame>
      <desc>Reported AEs are TEAEs i.e. AEs that developed/worsened during 'treatment period'(time from the first treatment administration to the last treatment administration + 30 days). Analysis was performed on safety population which included all participants who received at least 1 dose (or any partial dose) of SAR566658.</desc>
      <group_list>
        <group group_id="E1">
          <title>SAR566658 90 mg/m^2</title>
          <description>Participants received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
        </group>
        <group group_id="E2">
          <title>SAR566658 120 mg/m^2</title>
          <description>Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pancreatitis Acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Staphylococcal Bacteraemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastases To Meninges</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Ear Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Cushingoid</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal Sensation In Eye</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Corneal Epithelial Microcysts</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Corneal Opacity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry Eye</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Halo Vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Keratitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Keratopathy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Periorbital Oedema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vitreous Floaters</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Xerophthalmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Paraesthesia Oral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="11"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Device Related Thrombosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Hyperthermia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Oedema Peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Periodontitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Skin Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Tonsillitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Intentional Overdose</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood Bilirubin Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Transaminases Increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Weight Decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased Appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Muscle Spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neck Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Neuropathy Peripheral</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Peripheral Sensory Neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Breast Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Breast Ulceration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Metrorrhagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pleural Effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pulmonary Toxicity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Onychomadesis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Palmar-Plantar Erythrodysaesthesia Syndrome</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Pruritus Generalised</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was prematurely discontinued considering the limited clinical benefit combined with higher than expected rate of known non-serious ophthalmological event, hence Part 2 was not conducted and some of pre-specified endpoints were not analyzed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Trial Transparency Team</name_or_title>
      <organization>Sanofi aventis recherche &amp; développement</organization>
      <phone>800-633-1610 ext option 6</phone>
      <email>Contact-US@sanofi.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02984683
org study id: ACT14884
secondary id: 2016-001962-27
secondary id: U1111-1182-7044
nct id: NCT02984683
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Primary Objective:

      To evaluate the tumor Objective Response Rate (ORR), according to the Response Evaluation
      Criteria in Solid Tumors (RECIST 1.1) of SAR566658 in participants with anti-carbonic
      anhydrase 6 (CA6)-positive metastatic triple negative breast cancer (TNBC). Part 1: To select
      the SAR566658 dose based on ORR and safety of 2 dose levels of SAR566658. Part 2: Part 2a: To
      demonstrate the activity of SAR566658 based on ORR in participants overexpressing CA6
      (membrane intensity of 2+, 3+ in greater than or equal to (>=) 30% of tumor cells) treated at
      the selected dose in an expanded cohort, in addition to the participants treated in Part 1. -
      Part 2b: To assess the efficacy in participants with metastatic TNBC and mild CA6 expression.

      Secondary Objectives:

      To assess:

        -  Disease Control Rate (DCR), Duration of Response (DOR), Progression-Free Survival (PFS),
           and Time To Progression (TTP).

        -  The impact of ocular primary prophylaxis on the incidence of keratopathies.

        -  The potential immunogenicity of SAR566658.

        -  To evaluate the global safety profile.
The duration of the study for 1 participant included a screening period of up to 21 days
      prior to first study drug administration, 3-week treatment cycle(s) (until 30 days after last
      SAR566658 administration), and a follow-up period. Each participant was treated until
      radiological disease progression, unacceptable toxicity, or participant's refusal of further
      study treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings
time frame: Up to Cycle 2 (each cycle of 21 days)
description: Predefined safety criteria was defined as occurrence of following IMP-related treatment-emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade greater than or equal to (>=) 3 TEAE from the System Organ Class (SOC) of eye disorders, Grade >=3 peripheral neuropathy (Preferred Term), Grade >=4 TEAE. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE.
measure: Percentage of Participants With Objective Response
time frame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
description: Objective Response in participants was defined as the participants with complete response (CR) and partial response (PR) as best response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Percentage of Participants With Disease Control
time frame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
description: Disease control in participants was defined as the participants with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions) taking as reference the smallest sum diameters while on study.
measure: Duration of Response (DOR)
time frame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
description: DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the first radiological documentation of tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions.
measure: Progression Free Survival (PFS)
time frame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
description: PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumor progression or death (due to any cause), whichever comes first. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions.
measure: Time to Tumor Progression (TTP)
time frame: Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
description: TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumor progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study.
measure: Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)
time frame: Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)
description: AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.
measure: Number of Participants With Keratopathies (Corneal Toxicity)
time frame: Up to 30 days after last drug administration (maximum number of cycles was 3, each cycle 21 days)
description: Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All participants received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration.
measure: Number of Participants With Positive Anti-SAR566658 Antibodies Response
time frame: Up to 3 treatment cycles, each cycle 21 days
arm group label: SAR566658 90 mg/m^2
arm group type: Experimental
description: Participants received SAR566658 90 milligram per square meter (mg/m^2) as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
arm group label: SAR566658 120 mg/m^2
arm group type: Experimental
description: Participants received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
intervention type: Drug
intervention name: SAR566658 (ACT14884)
description: Pharmaceutical form:Solution Route of administration: Intravenous
arm group label: SAR566658 120 mg/m^2
arm group label: SAR566658 90 mg/m^2
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Sciences & Operations
role: Study Director
affiliation: Sanofi
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country: Belgium
country: Czechia
country: Italy
country: Netherlands
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was prematurely discontinued considering the limited clinical benefit combined with higher than expected rate of known non-serious ophthalmological event, hence Part 2 was not conducted and some of pre-specified endpoints were not analyzed.
point of contact: 