<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/NCT03009344</url>
  </required_header>
  <id_info>
    <org_study_id>E7438-J081-106</org_study_id>
    <nct_id>NCT03009344</nct_id>
  </id_info>
  <brief_title>A Study of Tazemetostat in Participants With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma</brief_title>
  <official_title>A Phase 1 Study of Tazemetostat in Patients With Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eisai Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multicenter, single-arm, open-label, Phase 1 study to assess the tolerability,&#xD;
      safety, pharmacokinetics, and preliminary anti-tumor activity of tazemetostat in participants&#xD;
      with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2017</start_date>
  <completion_date type="Actual">June 17, 2020</completion_date>
  <primary_completion_date type="Actual">July 12, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Dose-limiting Toxicities (DLTs)</measure>
    <time_frame>Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)</time_frame>
    <description>DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (&gt;) 7 days; 2) greater than or equal to (&gt;=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) &gt;=Grade 3 nausea, vomiting, or diarrhea that persisted &gt;7 days despite maximal medical therapy; 6) &gt;=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted &gt;7 days; 7) Other Grade 3 toxicity lasting &gt;7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer &gt;=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)</time_frame>
    <description>TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
    <description>Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F: Apparent Total Body Clearance of Tazemetostat</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
    <description>Vz/F for Cycle 0 Day 1 was calculated as Dose divided by ([lambda z]*[AUC0-infinity]) and for Cycle 1 Day 15 was calculated as Dose divided by ([lambda z]*[AUC0-tau]).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
    <description>MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
    <description>The PTF within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State</measure>
    <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
    <description>Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
    <description>Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
    <description>Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fe: Fraction of Tazemetostat Dose Excreted in Urine</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
    <description>The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose*100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR: Renal Clearance of Tazemetostat</measure>
    <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Objective Response</measure>
    <time_frame>From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months)</time_frame>
    <description>Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (&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>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma</condition>
  <arm_group>
    <arm_group_label>Tazemetostat 800 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later) (Cycle 0 duration=4 days) (Cycle 1 and later duration= 28 days).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tazemetostat</intervention_name>
    <description>Tazemetostat tablets.</description>
    <arm_group_label>Tazemetostat 800 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with histological diagnosis of B-cell non-Hodgkin's lymphoma&#xD;
&#xD;
          -  Participant who has measurable disease&#xD;
&#xD;
          -  Participant who had previous therapy with systemic chemotherapy and/or antibody&#xD;
             therapy&#xD;
&#xD;
          -  Participant who had progressive disease (PD) or did not have a response (complete&#xD;
             response [CR] or partial response [PR]) in previous systemic therapy, or relapsed or&#xD;
             progressed after previous systemic therapy&#xD;
&#xD;
          -  Participant with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to&#xD;
             1&#xD;
&#xD;
          -  Participant with life expectancy of ≥3 months from starting study drug administration&#xD;
&#xD;
          -  Participant with adequate renal, bone marrow, and liver function&#xD;
&#xD;
          -  Participant with left ventricular ejection fraction (LVEF) &gt; 50%&#xD;
&#xD;
          -  Male and female participant ≥20 years of age at the time of informed consent&#xD;
&#xD;
          -  Participant who has provided written consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant with prior exposure to EZH2 inhibitor&#xD;
&#xD;
          -  Participant with a history or a presence of central nerves invasion&#xD;
&#xD;
          -  Participant with allogeneic stem cell transplantation&#xD;
&#xD;
          -  Participant with medical need for the continued use of potent or moderate inhibitors&#xD;
             of CYP3A or P-gp, or potent or moderate inducer of CYP3A (including St. John's wort).&#xD;
&#xD;
          -  Participant with significant cardiovascular impairment&#xD;
&#xD;
          -  Participant with prolongation of corrected QT interval using Fridericia's formula&#xD;
             (QTcF) to &gt; 480 milliseconds (msec)&#xD;
&#xD;
          -  Participant with venous thrombosis or pulmonary embolism within the last 3 months&#xD;
             before starting study drug&#xD;
&#xD;
          -  Participant with complications of hepatic cirrhosis, interstitial pneumonia, or&#xD;
             pulmonary fibrosis&#xD;
&#xD;
          -  Participant with active infection requiring systemic therapy&#xD;
&#xD;
          -  Women of childbearing potential or man of impregnate potential who don't agree to use&#xD;
             a medically effective method for contraception for periods from before informed&#xD;
             consent to during the clinical study and 30 days later from last administration of&#xD;
             study drug&#xD;
&#xD;
          -  Woman who are pregnant or breastfeeding&#xD;
&#xD;
          -  Participant who were deemed as inappropriate to participate in the study by the&#xD;
             investigator or sub-investigator&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Eisai Trial Site</name>
      <address>
        <city>Isehara</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>December 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 4, 2017</study_first_posted>
  <results_first_submitted>January 12, 2022</results_first_submitted>
  <results_first_submitted_qc>April 6, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 10, 2022</results_first_posted>
  <last_update_submitted>April 6, 2022</last_update_submitted>
  <last_update_submitted_qc>April 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>relapsed or refractory B-cell non-Hodgkin's lymphoma</keyword>
  <keyword>tazemetostat</keyword>
  <keyword>Japan</keyword>
  <keyword>E7438</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Lymphoma, B-Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>October 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03009344/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>July 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/44/NCT03009344/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 2 investigative sites in Japan from 10 January 2017 to 17 June 2020.</recruitment_details>
      <pre_assignment_details>A total of 7 participants were screened and enrolled to receive study treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tazemetostat 800 mg</title>
          <description>Participants received tazemetostat 800 milligram (mg) tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until disease progression (PD), development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety/efficacy analysis set included all participants who received at least 1 administration of the study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Tazemetostat 800 mg</title>
          <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
          </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="72.3" spread="8.12"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Japanese</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Dose-limiting Toxicities (DLTs)</title>
        <description>DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (&gt;) 7 days; 2) greater than or equal to (&gt;=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) &gt;=Grade 3 nausea, vomiting, or diarrhea that persisted &gt;7 days despite maximal medical therapy; 6) &gt;=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted &gt;7 days; 7) Other Grade 3 toxicity lasting &gt;7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer &gt;=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported.</description>
        <time_frame>Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)</time_frame>
        <population>DLT analysis set included all participants who completed treatment Cycles 0 and 1 without major protocol deviations with at least 75% of treatment compliance in Cycle 1 and were assessed for DLT, and participants who experienced DLT during Cycles 0 and 1. Participants with less than 75% treatment compliance in Cycle 1 due to a reason other than toxicity up to Cycle 1 Day 28 were not included in this analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Dose-limiting Toxicities (DLTs)</title>
          <description>DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (&gt;) 7 days; 2) greater than or equal to (&gt;=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) &gt;=Grade 3 nausea, vomiting, or diarrhea that persisted &gt;7 days despite maximal medical therapy; 6) &gt;=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted &gt;7 days; 7) Other Grade 3 toxicity lasting &gt;7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer &gt;=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported.</description>
          <population>DLT analysis set included all participants who completed treatment Cycles 0 and 1 without major protocol deviations with at least 75% of treatment compliance in Cycle 1 and were assessed for DLT, and participants who experienced DLT during Cycles 0 and 1. Participants with less than 75% treatment compliance in Cycle 1 due to a reason other than toxicity up to Cycle 1 Day 28 were not included in this analysis set.</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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
        <description>TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria.</description>
        <time_frame>From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)</time_frame>
        <population>The safety analysis set included all participants who received at least 1 administration of the study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
          <description>TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria.</description>
          <population>The safety analysis set included all participants who received at least 1 administration of the study drug.</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="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The pharmacokinetic (PK) analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The pharmacokinetic (PK) analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="988" spread="62.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="790" spread="78.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.97" lower_limit="0.95" upper_limit="4.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.97" lower_limit="1.12" upper_limit="4.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>nanogram*hour per milliliter (ng*h/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4080" spread="61.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4500" spread="72.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5180" spread="63.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6540" spread="75.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5220" spread="63.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6570" spread="74.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387</title>
        <description>Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.</description>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387</title>
          <description>Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>per hour</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0925" spread="17.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0794" spread="16.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat (Cycle 0 Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.76" lower_limit="5.24" upper_limit="9.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tazemetostat (Cycle 1 Day 15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.10" lower_limit="2.40" upper_limit="8.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387 (Cycle 0 Day 1)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.68" lower_limit="6.52" upper_limit="10.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387 (Cycle 1 Day 15)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.55" lower_limit="3.22" upper_limit="9.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CL/F: Apparent Total Body Clearance of Tazemetostat</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>CL/F: Apparent Total Body Clearance of Tazemetostat</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>liter per hour (L/h)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="153" spread="63.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat</title>
        <description>Vz/F for Cycle 0 Day 1 was calculated as Dose divided by ([lambda z]*[AUC0-infinity]) and for Cycle 1 Day 15 was calculated as Dose divided by ([lambda z]*[AUC0-tau]).</description>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat</title>
          <description>Vz/F for Cycle 0 Day 1 was calculated as Dose divided by ([lambda z]*[AUC0-infinity]) and for Cycle 1 Day 15 was calculated as Dose divided by ([lambda z]*[AUC0-tau]).</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>liter (L)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0 Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1660" spread="64.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1170" spread="93.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387</title>
        <description>MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time.</description>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387</title>
          <description>MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time.</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.25" spread="29.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.7" spread="31.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4220" spread="42.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10200" spread="39.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="351" spread="42.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="852" spread="39.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1170" spread="51.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1800" spread="47.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.4" spread="43.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="293" spread="46.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387</title>
        <description>The PTF within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.</description>
        <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387</title>
          <description>The PTF within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>percentage fluctuation</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="303" spread="40.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="171" spread="39.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387</title>
        <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.05" lower_limit="0.88" upper_limit="2.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.07" lower_limit="0.88" upper_limit="2.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State</title>
        <time_frame>Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="190" spread="42.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387</title>
        <description>Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1.</description>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387</title>
          <description>Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1.</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.19" spread="56.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.28" spread="59.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387</title>
        <description>Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1.</description>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387</title>
          <description>Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1.</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.04" spread="37.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.27" spread="58.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387</title>
        <description>Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1.</description>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387</title>
          <description>Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1.</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tazemetostat</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.809" spread="35.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ER-897387</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.56" spread="53.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed &quot;n&quot; signifies participants who were evaluable for this outcome measure at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed &quot;n&quot; signifies participants who were evaluable for this outcome measure at given time points.</population>
          <units>mg</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.1" spread="51.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.81" spread="33.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Fe: Fraction of Tazemetostat Dose Excreted in Urine</title>
        <description>The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose*100.</description>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed &quot;n&quot; signifies participants who were evaluable for this outcome measure at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Fe: Fraction of Tazemetostat Dose Excreted in Urine</title>
          <description>The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose*100.</description>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed &quot;n&quot; signifies participants who were evaluable for this outcome measure at given time points.</population>
          <units>percentage of dose</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.89" spread="51.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.852" spread="33.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CLR: Renal Clearance of Tazemetostat</title>
        <time_frame>Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)</time_frame>
        <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed &quot;n&quot; signifies participants who were evaluable for this outcome measure at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>CLR: Renal Clearance of Tazemetostat</title>
          <population>The PK analysis set included all participants who received at least 1 administration of the study drug and had sufficient PK data to derive at least 1 PK parameter. Here number analyzed &quot;n&quot; signifies participants who were evaluable for this outcome measure at given time points.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 0 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.62" spread="15.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.62" spread="25.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Objective Response</title>
        <description>Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (&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>From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months)</time_frame>
        <population>The efficacy analysis set included all participants who received at least 1 administration of the study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Tazemetostat 800 mg</title>
            <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Objective Response</title>
          <description>Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (&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>The efficacy analysis set included all participants who received at least 1 administration of the study drug.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.1" lower_limit="18.4" upper_limit="90.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)</time_frame>
      <desc>The safety analysis set included all participants who received at least 1 administration of the study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tazemetostat 800 mg</title>
          <description>Participants received tazemetostat 800 mg tablets, orally on Day 1 of Cycle 0 and 800 mg tablets, orally, twice daily as continuous dosing in Cycle 1 and later cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or study termination by the sponsor (up to 39 months). Cycle 0 duration was 4 days, Cycle 1 and later cycles duration was 28 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.0</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="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intestinal perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Squamous cell carcinoma of the tongue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 22.0</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="7" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Anal fissure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Epigastric discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Muscle strain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Blood triglycerides increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperphosphatasaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bursitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Haemarthrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Synovial cyst</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour associated fever</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Neuropathy peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Middle insomnia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nail disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin swelling</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Inquiry Service</name_or_title>
      <organization>Eisai Co., Ltd.</organization>
      <email>eisai-chiken_hotline@hhc.eisai.co.jp</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/NCT03009344
org study id: E7438-J081-106
nct id: NCT03009344
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a multicenter, single-arm, open-label, Phase 1 study to assess the tolerability,
      safety, pharmacokinetics, and preliminary anti-tumor activity of tazemetostat in participants
      with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Dose-limiting Toxicities (DLTs)
time frame: Cycle 0 and Cycle 1 (Cycle 0=4 days, Cycle 1=28 days)
description: DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) were defined as: 1) Grade 4 neutropenia for greater than (>) 7 days; 2) greater than or equal to (>=) Grade 3 febrile neutropenia; 3) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 4) Grade 4 anemia or anemia requiring erythrocyte transfusion; 5) >=Grade 3 nausea, vomiting, or diarrhea that persisted >7 days despite maximal medical therapy; 6) >=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted >7 days; 7) Other Grade 3 toxicity lasting >7 days or Grade 4 non-hematological toxicity of any duration; 8) Failure to administer >=75 percent (%) of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity. Here, number of participants who had DLT were reported.
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: From the date of first dose up to 30 days after the last dose of study drug (up to 40 months)
description: TEAE was defined as an adverse event (AE) that emerged during time from first dose to 30 days following last dose of drug, having been absent at pretreatment or reemerged during treatment, having been present at pretreatment but stopped before treatment, or worsened in severity during treatment relative to pretreatment state, when AE was continuous. Number of participants with TEAEs were reported based on their safety assessments of laboratory tests, physical examination, regular measurement of vital signs, body weight, echocardiograms/multigated acquisition (MUGA) scans to assess left ventricular ejection fraction, eastern cooperative oncology group-performance status (ECOG-PS) and electrocardiograms parameter values. SAE was defined as untoward medical occurrence that at any dose resulted in death; was life threatening; resulted in persistent or significant disability; was congenital anomaly or medically important due to other reasons than above mentioned criteria.
measure: Cmax: Maximum Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: Tmax: Time to Reach Maximum Plasma Concentration (Cmax) of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: AUC(0-12 Hours): Area Under the Plasma Concentration-time Curve From Time Zero to 12 Hours Post-dose of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-12 hours post-dose (Cycle 0 length=4 days)
measure: AUC(0-t Hours): Area Under the Plasma Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: AUC(0-infinity): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: Lambda z: Terminal Phase Elimination Rate Constant of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
description: Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method.
measure: T1/2: Terminal Half-life of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: CL/F: Apparent Total Body Clearance of Tazemetostat
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
measure: Vz/F: Apparent Volume of Distribution at Terminal Phase of Tazemetostat
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
description: Vz/F for Cycle 0 Day 1 was calculated as Dose divided by ([lambda z]*[AUC0-infinity]) and for Cycle 1 Day 15 was calculated as Dose divided by ([lambda z]*[AUC0-tau]).
measure: MRT: Mean Residence Time of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days)
description: MRT of tazemetostat and its metabolite ER-897387 was calculated as MRT=AUMC(0-infinity)/AUC(0-infinity), where AUMC(0-infinity) was the area under the first moment curve extrapolated to infinity and AUC(0-infinity) was area under the concentration-time curve from zero time extrapolated to infinite time.
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Css,Av: Average Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Css,Max: Maximum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Css,Min: Minimum Steady State Plasma Concentration of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: PTF: Peak-trough Fluctuation Ratio of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
description: The PTF within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav) multiplied by 100. Here, Cmin means the minimum plasma concentration, Cmax means the maximum plasma concentration and Cav means the average plasma concentration of drug and metabolite.
measure: Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: CLss/F: Apparent Total Body Clearance of Tazemetostat at Steady State
time frame: Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Rac (Cmax): Accumulation Ratio of Cmax for Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
description: Rac (Cmax) was calculated as the ratio of maximum observed concentration at steady state (Css,max) on Cycle 1 Day 15 divided by Cmax on Cycle 0 Day 1.
measure: Rac (AUC): Accumulation Ratio of AUC for Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
description: Rac (AUC) was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-12 hours) on Cycle 0 Day 1.
measure: Rss: Steady State Accumulation Ratio of Tazemetostat and Its Metabolite ER-897387
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days) and Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
description: Rss was calculated as the ratio of AUC(0-tau) on Cycle 1 Day 15 divided by AUC(0-infinity) on Cycle 0 Day 1.
measure: Ae: Amount of Unchanged Drug Tazemetostat Excreted in Urine
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Fe: Fraction of Tazemetostat Dose Excreted in Urine
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
description: The fraction of dose excreted in urine was calculated as: Cumulative amount of unchanged drug excreted in urine (Ae)/Dose*100.
measure: CLR: Renal Clearance of Tazemetostat
time frame: Cycle 0 Day 1: 0-72 hours post-dose (Cycle 0 length=4 days); Cycle 1 Day 15: 0-12 hours post-dose (Cycle 1 length=28 days)
measure: Percentage of Participants With Objective Response
time frame: From the date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurred first (up to 39 months)
description: Objective response was assessed by investigator based on the Lugano Classification (CT-Based) response criteria. Objective response rate was defined as the percentage of participants who had a Best Overall Response (BOR) of complete response (CR) or partial response (PR). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis to less than (<) 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.
arm group label: Tazemetostat 800 mg
arm group type: Experimental
description: Participants will receive oral tazemetostat at a starting dose of 800 milligrams (mg) as a single dose (Cycle 0) and 800 mg twice a day as continuous dosing (Cycle 1 and later) (Cycle 0 duration=4 days) (Cycle 1 and later duration= 28 days).
intervention type: Drug
intervention name: Tazemetostat
description: Tazemetostat tablets.
arm group label: Tazemetostat 800 mg
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Lymphoma, B-Cell
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 