<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/NCT03006887</url>
  </required_header>
  <id_info>
    <org_study_id>E7080-J081-115</org_study_id>
    <secondary_id>KEYNOTE 523</secondary_id>
    <nct_id>NCT03006887</nct_id>
  </id_info>
  <brief_title>Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Participants With Selected Solid Tumors</brief_title>
  <official_title>An Open-Label Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Subjects With Selected Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eisai Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label Phase 1b study designed to confirm the tolerability and safety of&#xD;
      lenvatinib in combination with pembrolizumab in participants with selected solid tumors&#xD;
      (non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial&#xD;
      carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma&#xD;
      [excluding uveal melanoma]).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 12, 2017</start_date>
  <completion_date type="Actual">April 15, 2020</completion_date>
  <primary_completion_date type="Actual">April 15, 2020</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 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From the first dose until 30 days after the last dose (approximately 2 years 7 months)</time_frame>
    <description>A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Dose-limiting Toxicities</measure>
    <time_frame>Cycle 1 (Cycle length=21 days)</time_frame>
    <description>A DLT is defined as any of the following: any of the hematological or nonhematological toxicities specified in the protocol that are considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; failed to administer greater than or equal to 75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; participants who discontinued due to treatment-related toxicity in Cycle 1; greater than a 2-week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</measure>
    <time_frame>From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months</time_frame>
    <description>ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</measure>
    <time_frame>From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months.</time_frame>
    <description>DOR was defined as time from the first documented of CR or PR to the date of first documentation of disease progression (PD) (based on modified RECIST 1.1) or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. DOR = Date of PD/death (whichever occurs first) - Date of first CR or PR + 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours</time_frame>
    <description>Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (Cmax) = Css,max on Cycle 1 Day 15 / Cmax on Cycle 1 Day 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours</time_frame>
    <description>Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC) = AUC(0-t) on Cycle 1 Day 15 / AUC(0-t) on Cycle 1 Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab</measure>
    <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
    <description>The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab</measure>
    <time_frame>Day 1 of Cycles 1, 2, 4, 6, and 8 and every 4 cycles thereafter; within 30 days after discontinuation or until the initiation of other anticancer treatment, whichever is earlier (Cycle length=21 days); up to 31 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>lenvatinib 20 mg plus pembrolizumab 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with selected tumors will receive oral lenvatinib at a starting dose of 20 milligrams (mg) once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lenvatinib</intervention_name>
    <description>lenvatinib capsules</description>
    <arm_group_label>lenvatinib 20 mg plus pembrolizumab 200 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>pembrolizumab intravenous infusion</description>
    <arm_group_label>lenvatinib 20 mg plus pembrolizumab 200 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically and/or cytologically confirmed selected solid tumor types that have&#xD;
             progressed after treatment with standard therapies or for which there are no other&#xD;
             appropriate therapies available.&#xD;
&#xD;
        The selected tumor types are: non-small cell lung cancer, predominantly clear cell renal&#xD;
        cell carcinoma, endometrial carcinoma, urothelial carcinoma, squamous cell carcinoma of the&#xD;
        head and neck, or melanoma (excluding uveal melanoma)&#xD;
&#xD;
          -  At least 1 measurable target lesion according to modified Response Evaluation Criteria&#xD;
             In Solid Tumors (RECIST) 1.1&#xD;
&#xD;
          -  Participants must have an Eastern Cooperative Oncology Group (ECOG)-Performance Status&#xD;
             (PS) of 0 to 1.&#xD;
&#xD;
          -  Adequate liver function as evidenced by bilirubin ≤1.5×ULN and alkaline phosphatase&#xD;
             (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3×ULN (in&#xD;
             the case of liver metastases ≤5×ULN). In case ALP is &gt;3×ULN (in the absence of liver&#xD;
             metastases) or &gt;5×ULN (in the presence of liver metastases) AND the participant also&#xD;
             is known to have bone metastases, the liver-specific ALP must be separated from the&#xD;
             total and used to assess the liver function instead of the total ALP.&#xD;
&#xD;
          -  Males or females age ≥20 years at the time of informed consent&#xD;
&#xD;
          -  Life expectancy of 12 weeks or more&#xD;
&#xD;
          -  Voluntary agreement to provide written informed consent and the willingness and&#xD;
             ability to comply with all aspects of the protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior anticancer treatment within 28 days (or 5 times the half-life time, whichever is&#xD;
             shorter) or any investigational agent within 28 days prior to the first dose of study&#xD;
             drugs. All toxicities related to prior treatments must be resolved to Grade ≤1 (except&#xD;
             alopecia).&#xD;
&#xD;
          -  Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent,&#xD;
             excluding cancer types such as melanoma and non-small cell lung cancer where prior&#xD;
             treatment with one anti-PD-1, anti-PD-L1, or anti-PD-L2 agent is allowed&#xD;
&#xD;
          -  Participants must have recovered adequately from any complications from major surgery&#xD;
             prior to starting therapy.&#xD;
&#xD;
          -  New York Heart Association congestive heart failure of grade II or above, unstable&#xD;
             angina, myocardial infarction within the past 6 months, or serious cardiac arrhythmia&#xD;
             associated with significant cardiovascular impairment within the past 6 months&#xD;
&#xD;
          -  Prolongation of QTc (Fridericia formula) interval to &gt;480 milliseconds (ms)&#xD;
&#xD;
          -  Active infection (any infection requiring systemic treatment)&#xD;
&#xD;
          -  Participant is known to be positive for Human Immunodeficiency Virus (HIV), Hepatitis&#xD;
             B, or Hepatitis C&#xD;
&#xD;
          -  Known intolerance to either of the study drugs (or any of the excipients)&#xD;
&#xD;
          -  History of organ allograft&#xD;
&#xD;
          -  Any medical or other condition which, in the opinion of the investigator, would&#xD;
             preclude participation in a clinical trial&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis, or has a history of interstitial lung disease&#xD;
&#xD;
          -  Females who are breastfeeding or pregnant at Screening or Baseline.&#xD;
&#xD;
          -  Females of childbearing potential.&#xD;
&#xD;
          -  Participants must be on a stable dose of the same oral hormonal contraceptive product&#xD;
             for at least 4 weeks before dosing with study drug and for the duration of the study.&#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 1</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 2021</verification_date>
  <study_first_submitted>December 27, 2016</study_first_submitted>
  <study_first_submitted_qc>December 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <results_first_submitted>April 15, 2021</results_first_submitted>
  <results_first_submitted_qc>May 19, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 20, 2021</results_first_posted>
  <last_update_submitted>May 19, 2021</last_update_submitted>
  <last_update_submitted_qc>May 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>solid tumors</keyword>
  <keyword>non-small cell lung cancer</keyword>
  <keyword>predominantly clear cell renal cell carcinoma</keyword>
  <keyword>endometrial carcinoma</keyword>
  <keyword>urothelial carcinoma</keyword>
  <keyword>squamous cell carcinoma of the head and neck</keyword>
  <keyword>non-uveal melanoma</keyword>
  <keyword>E7080</keyword>
  <keyword>lenvatinib</keyword>
  <keyword>pembrolizumab</keyword>
  <keyword>Japan</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Lenvatinib</mesh_term>
  </intervention_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>April 7, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03006887/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>October 11, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03006887/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 1 investigative site in Japan from 12 Jan 2017 to 15 Apr 2020.</recruitment_details>
      <pre_assignment_details>A total of 11 participants were screened, of which 5 were screen failures and 6 received study treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
          <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 milligram (mg), capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing Dose limiting toxicities (DLTs). In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <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 analysis set included all participants who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
          <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </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="55.0" spread="13.39"/>
                  </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="3"/>
                  </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="6"/>
                  </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 (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
        <description>A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.</description>
        <time_frame>From the first dose until 30 days after the last dose (approximately 2 years 7 months)</time_frame>
        <population>The safety analysis set included all participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
          <description>A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.</description>
          <population>The safety analysis set included all participants who received at least 1 dose of 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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Dose-limiting Toxicities</title>
        <description>A DLT is defined as any of the following: any of the hematological or nonhematological toxicities specified in the protocol that are considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; failed to administer greater than or equal to 75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; participants who discontinued due to treatment-related toxicity in Cycle 1; greater than a 2-week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria.</description>
        <time_frame>Cycle 1 (Cycle length=21 days)</time_frame>
        <population>The DLT set included all participants who completed Cycle 1 without major protocol deviation with at least 75% of study drug compliance and were assessed for DLT, and participants who experienced DLT during Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Dose-limiting Toxicities</title>
          <description>A DLT is defined as any of the following: any of the hematological or nonhematological toxicities specified in the protocol that are considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; failed to administer greater than or equal to 75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; participants who discontinued due to treatment-related toxicity in Cycle 1; greater than a 2-week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria.</description>
          <population>The DLT set included all participants who completed Cycle 1 without major protocol deviation with at least 75% of study drug compliance and were assessed for DLT, and participants who experienced DLT during Cycle 1.</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>Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</title>
        <description>ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.</description>
        <time_frame>From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months</time_frame>
        <population>The efficacy analysis set included all participants who received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</title>
          <description>ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.</description>
          <population>The efficacy analysis set included all participants who received at least 1 dose of study drug.</population>
          <units>percentage of participants</units>
          <param>Number</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="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</title>
        <description>DOR was defined as time from the first documented of CR or PR to the date of first documentation of disease progression (PD) (based on modified RECIST 1.1) or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. DOR = Date of PD/death (whichever occurs first) - Date of first CR or PR + 1.</description>
        <time_frame>From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months.</time_frame>
        <population>The efficacy analysis set included all participants who received at least 1 dose of study drug. Here overall number analyzed &quot;N&quot; included the participants who had CR or PR.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</title>
          <description>DOR was defined as time from the first documented of CR or PR to the date of first documentation of disease progression (PD) (based on modified RECIST 1.1) or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. DOR = Date of PD/death (whichever occurs first) - Date of first CR or PR + 1.</description>
          <population>The efficacy analysis set included all participants who received at least 1 dose of study drug. Here overall number analyzed &quot;N&quot; included the participants who had CR or PR.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="16.79" upper_limit="NA">Median and upper limit of 95%CI was not estimable due to lesser number of participants with events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <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="325" spread="233"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.85" lower_limit="1.78" upper_limit="7.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</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="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.62" lower_limit="5.52" upper_limit="5.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.26" lower_limit="6.95" upper_limit="7.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
          <units>nanogram*hour per milliliter (ng*h/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <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>
              <title>Cycle 1 Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3040" spread="1780"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4280" spread="2600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3880" spread="2090"/>
                  </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 Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>liter (L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.8" spread="23.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.1" spread="0.636"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here, overall number analyzed &quot;N&quot; are the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here, overall number analyzed &quot;N&quot; are the participants who were evaluable for the outcome measure.</population>
          <units>liter per hour (L/hr)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.15" spread="2.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>hours</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.06" spread="0.983"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.8" spread="0.141"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <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="355" spread="319"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <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="60.1" spread="24.6"/>
                  </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 Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</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="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.14" lower_limit="2.07" upper_limit="7.83"/>
                  </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 Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>ng*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6780" spread="1820"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.95" spread="0.932"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="283" spread="75.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab</title>
        <description>Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (Cmax) = Css,max on Cycle 1 Day 15 / Cmax on Cycle 1 Day 1</description>
        <time_frame>Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab</title>
          <description>Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (Cmax) = Css,max on Cycle 1 Day 15 / Cmax on Cycle 1 Day 1</description>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <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="1.14" spread="0.376"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab</title>
        <description>Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC) = AUC(0-t) on Cycle 1 Day 15 / AUC(0-t) on Cycle 1 Day 1.</description>
        <time_frame>Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab</title>
          <description>Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC) = AUC(0-t) on Cycle 1 Day 15 / AUC(0-t) on Cycle 1 Day 1.</description>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
          <units>ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <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="1.46" spread="0.450"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab</title>
        <time_frame>Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>1/hour</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.123" spread="0.00354"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0956" spread="0.00573"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab</title>
        <description>The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100</description>
        <time_frame>Cycle 1 Day 15: 0-24 hours</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab</title>
          <description>The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100</description>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data. Here overall number analyzed &quot;N&quot; included the participants who were evaluable for the outcome measure.</population>
          <units>Percentage fluctuation</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="194" spread="48.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab</title>
        <time_frame>Day 1 of Cycles 1, 2, 4, 6, and 8 and every 4 cycles thereafter; within 30 days after discontinuation or until the initiation of other anticancer treatment, whichever is earlier (Cycle length=21 days); up to 31 months</time_frame>
        <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</population>
        <group_list>
          <group group_id="O1">
            <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
            <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab</title>
          <population>The PK analysis set included all participants who received at least 1 dose of lenvatinib and pembrolizumab, and had evaluable concentration data.</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_list>

    <reported_events>
      <time_frame>Baseline up to 30 days after last dose of study drug (approximately 2 years 7 months)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Lenvatinib 20 mg Plus Pembrolizumab 200 mg</title>
          <description>Participants with selected solid tumors received oral lenvatinib at a starting dose of 20 mg, capsule, once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks on a 21-day treatment cycle to confirm the dose tolerability by assessing DLTs. In case of dose intolerability in Cycle 1, lenvatinib dose was reduced from 20 mg to 14 mg once daily, in combination with 200 mg pembrolizumab every 3 weeks administered up to maximum of 45 cycles or until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study (31 months).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (22.1)</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="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Subileus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Aspergillus infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (22.1)</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="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Performance status decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Gallbladder enlargement</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Bronchopulmonary aspergillosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Tooth infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Post procedural haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Thermal burn</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood cholesterol increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Electrocardiogram ST-T change</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hyperphosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Hypozincaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Periarthritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </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="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Purpura</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
              </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 NOT 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, Inc.</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/NCT03006887
org study id: E7080-J081-115
secondary id: KEYNOTE 523
nct id: NCT03006887
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is an open-label Phase 1b study designed to confirm the tolerability and safety of
      lenvatinib in combination with pembrolizumab in participants with selected solid tumors
      (non-small cell lung cancer, predominantly clear cell renal cell carcinoma, endometrial
      carcinoma, urothelial carcinoma, squamous cell carcinoma of the head and neck, or melanoma
      [excluding uveal melanoma]).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: From the first dose until 30 days after the last dose (approximately 2 years 7 months)
description: A TEAE was defined as an adverse event (AE) that emerged during the time from the first dose of study drug to 30 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. A Serious AE is any untoward medical occurrence that at any dose: resulted in death; was life threatening (that is, the participant was at immediate risk of death from the AE as it occurred; this does not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death) required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect or is medically important due to other reasons than the above mentioned criteria.
measure: Number of Participants With Dose-limiting Toxicities
time frame: Cycle 1 (Cycle length=21 days)
description: A DLT is defined as any of the following: any of the hematological or nonhematological toxicities specified in the protocol that are considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; failed to administer greater than or equal to 75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; participants who discontinued due to treatment-related toxicity in Cycle 1; greater than a 2-week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria.
measure: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months
description: ORR was defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) for target and non-target lesions. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (target or non-target) had to be reduced in the short axis to less than 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ.
measure: Duration of Response (DOR) Based on Modified Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or up to approximately 2 years 7 months.
description: DOR was defined as time from the first documented of CR or PR to the date of first documentation of disease progression (PD) (based on modified RECIST 1.1) or death (whichever occurs first). CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. PD for target lesion, was defined as a minimum 20% increase and a minimum 5 mm absolute increase in sum of diameters compared to nadir, or PD for non-target lesion(s) or unequivocal new lesion(s). Nadir was defined as lowest measure sum of diameters of target lesions at any time point from baseline onward. The tumor assessment was done using number of lesions based on modified RECIST 1.1 for assessing tumor burden up to 10 target lesions with up to 5 target lesions per organ. DOR = Date of PD/death (whichever occurs first) - Date of first CR or PR + 1.
measure: Cmax: Maximum Plasma Concentration of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours
measure: T1/2: Terminal Half-life of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: AUC(0-t): Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: AUC(0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours
measure: Vz/F: Apparent Volume of Distribution at Terminal Phase of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: CL/F: Apparent Total Clearance Following Oral Dosing of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours
measure: MRT: Mean Residence Time of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: Css,Max: Maximum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 15: 0-24 hours
measure: Css,Min: Minimum Observed Plasma Concentration at Steady State of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 15: 0-24 hours
measure: Tss,Max: Time to Reach the Maximum Plasma Concentration (Cmax) at Steady State of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 15: 0-24 hours
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 15: 0-24 hours
measure: Clss/F: Apparent Total Clearance Following Oral Administration at Steady State of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 15: 0-24 hours
measure: Css,Av: Average Steady State Plasma Concentration of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 15: 0-24 hours
measure: Rac (Cmax): Accumulation Index of Cmax for Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
description: Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (Cmax) = Css,max on Cycle 1 Day 15 / Cmax on Cycle 1 Day 1
measure: Rac (AUC): Accumulation Index of AUC for Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours and Cycle 1 Day 15: 0-24 hours
description: Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Rac (AUC) = AUC(0-t) on Cycle 1 Day 15 / AUC(0-t) on Cycle 1 Day 1.
measure: Lambda z: Terminal Phase Elimination Rate Constant of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 1: 0-24 hours; Cycle 1 Day 15: 0-24 hours
measure: PTF: Peak-trough Fluctuation Ratio of Lenvatinib in Combination With Pembrolizumab
time frame: Cycle 1 Day 15: 0-24 hours
description: The peak trough fluctuation within complete dosing interval at steady state, calculated as PTF (%) = ([Cmax - Cmin]/Cav ) multiplied by 100
measure: Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab
time frame: Day 1 of Cycles 1, 2, 4, 6, and 8 and every 4 cycles thereafter; within 30 days after discontinuation or until the initiation of other anticancer treatment, whichever is earlier (Cycle length=21 days); up to 31 months
arm group label: lenvatinib 20 mg plus pembrolizumab 200 mg
arm group type: Experimental
description: Participants with selected tumors will receive oral lenvatinib at a starting dose of 20 milligrams (mg) once daily in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination of the study.
intervention type: Drug
intervention name: lenvatinib
description: lenvatinib capsules
arm group label: lenvatinib 20 mg plus pembrolizumab 200 mg
intervention type: Drug
intervention name: pembrolizumab
description: pembrolizumab intravenous infusion
arm group label: lenvatinib 20 mg plus pembrolizumab 200 mg
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Pembrolizumab
mesh term: Lenvatinib
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 