<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/NCT03006926</url>
  </required_header>
  <id_info>
    <org_study_id>E7080-J081-116</org_study_id>
    <secondary_id>KEYNOTE 524</secondary_id>
    <secondary_id>2018-000522-55</secondary_id>
    <nct_id>NCT03006926</nct_id>
  </id_info>
  <brief_title>A Trial of Lenvatinib Plus Pembrolizumab in Participants With Hepatocellular Carcinoma</brief_title>
  <official_title>An Open-Label Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Subjects With Hepatocellular Carcinoma</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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label Phase 1b study designed to evaluate the tolerability and safety of&#xD;
      lenvatinib in combination with pembrolizumab in participants with hepatocellular carcinoma&#xD;
      (HCC). The study will evaluate objective response rate and duration of response by modified&#xD;
      Response Evaluation Criteria In Solid Tumors (mRECIST) for HCC and Response Evaluation&#xD;
      Criteria In Solid Tumors (RECIST 1.1) based on independent imaging review (IIR).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 13, 2017</start_date>
  <completion_date type="Actual">November 22, 2022</completion_date>
  <primary_completion_date type="Actual">October 31, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From first dose until 30 days after the last dose (up to approximately 2 years 9 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Expansion Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From first dose until 30 days after the last dose (up to approximately 2 years 9 months)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>DLT Part: Number of Participants With Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>From first dose of study drug up to Cycle 1 Day 21 (Cycle length= 21 days)</time_frame>
    <description>DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following: (1) any of the hematological or nonhematological toxicities considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; (2) failure to &gt;=75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; (3) participants who discontinue treatment due to treatment-related toxicity in Cycle 1; (4) &gt;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>
  <primary_outcome>
    <measure>DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST and RECIST 1.1 Assessed by Independent Imaging Review (IIR)</measure>
    <time_frame>From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
    <description>ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by IIR analysis. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 millimeter [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the long diameter (LD) (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by IIR</measure>
    <time_frame>From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
    <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on mRECIST assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>DLT+Expansion Part: Duration of Response (DOR) Based on RECIST 1.1 Assessed by IIR</measure>
    <time_frame>From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
    <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST Assessed by Investigator Review</measure>
    <time_frame>From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
    <description>ORR was defined as the percentage of participants who had BOR of CR or PR based on mRECIST assessed by investigator review. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by Investigator Review</measure>
    <time_frame>From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
    <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) based on mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Progression-free Survival (PFS) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review</measure>
    <time_frame>From the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) (up to approximately 2 years 9 months)</time_frame>
    <description>PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on mRECIST and RECIST 1.1 assessed by IIR, and mRECIST assessed by investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Time-to Progression (TTP) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review</measure>
    <time_frame>From date of first dose of study drug until disease progression (up to approximately 2 years 9 months)</time_frame>
    <description>TTP was defined as the time from the first study dose date to the date of first documentation of PD, based on mRECIST and RECIST 1.1 assessed by IIR and mRECIST assessed by an investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by IIR</measure>
    <time_frame>From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)</time_frame>
    <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Time-to Response (TTR) Based on RECIST 1.1 Assessed by IIR</measure>
    <time_frame>From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)</time_frame>
    <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to RECIST 1.1 assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by Investigator Review</measure>
    <time_frame>From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)</time_frame>
    <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DLT+Expansion Part: Overall Survival (OS)</measure>
    <time_frame>From the date of first dose of study drug until date of death from any cause (up to approximately 2 years 9 months)</time_frame>
    <description>OS was measured from the date of first dose of study drug until date of death from any cause. Participants who were lost to follow-up and the participants who were alive at the date of data cutoff was censored at the date the participant was last known alive, whichever came earlier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach the Cmax for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-ti): Area Under The Plasma Concentration-time Curve From Zero (Pre-Dose) to a Given Sampling Time (ti) for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2: Terminal Elimination Phase Half-Life for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F: Apparent Total Clearance for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F: Apparent Volume of Distribution at Terminal Phase for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tss,Max: Time to Maximum Concentration at Steady State For Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clss/F: Apparent Total Clearance Following Oral Administration at Steady State for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Css,Av: Average Steady State Plasma Concentration for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rac (Cmax): Accumulation Index of Cmax for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</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. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rac (AUC): Accumulation Index of AUC for Lenvatinib and Pembrolizumab</measure>
    <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</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. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab</measure>
    <time_frame>Cycles 1 and 6 Day 1: Pre-dose (cycle length=21 days)</time_frame>
    <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">104</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>lenvatinib 8 or 12 mg plus pembrolizumab 200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive oral lenvatinib at a starting dose of 8 or 12 milligrams (mg) once a day (QD) in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle. The starting dose of lenvatinib will be based on Baseline body weight. Participants weighing greater than or equal to 60 kilograms (kg) will receive 12 mg QD; participants weighing less than 60 kg will receive 8 mg QD.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>lenvatinib</intervention_name>
    <description>4 mg capsules</description>
    <arm_group_label>lenvatinib 8 or 12 mg plus pembrolizumab 200 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab (200 mg)</intervention_name>
    <description>30-minute intravenous infusion</description>
    <arm_group_label>lenvatinib 8 or 12 mg plus pembrolizumab 200 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Confirmed diagnosis of hepatocellular carcinoma (HCC)&#xD;
&#xD;
          -  HCC for which no other appropriate therapy is available. Note: Expansion Part: No&#xD;
             prior systemic therapy for advanced/unresectable HCC&#xD;
&#xD;
          -  Stage B (not applicable for transarterial chemoembolization [TACE]), or stage C based&#xD;
             on Barcelona Clinic Liver Cancer (BCLC) staging system&#xD;
&#xD;
          -  At least 1 measurable target lesion according to modified Response Evaluation Criteria&#xD;
             in Solid Tumors (mRECIST)&#xD;
&#xD;
          -  Child-Pugh score A&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1&#xD;
&#xD;
          -  Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within normal&#xD;
             limits. (control by thyroid replacement therapy is acceptable.) Participants with T3,&#xD;
             free T3 or free T4 abnormalities at screening who are asymptomatic can be eligible&#xD;
&#xD;
          -  Adequately controlled blood pressure&#xD;
&#xD;
          -  Adequate renal function&#xD;
&#xD;
          -  Adequate bone marrow function&#xD;
&#xD;
          -  Adequate blood coagulation function&#xD;
&#xD;
          -  Adequate liver function&#xD;
&#xD;
          -  Males or females age ≥ 18 years at the time of informed consent&#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 treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent&#xD;
&#xD;
          -  Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or&#xD;
             squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the&#xD;
             past 36 months&#xD;
&#xD;
          -  Any medical or other condition which, in the opinion of the investigator, would&#xD;
             preclude participation in a clinical trial&#xD;
&#xD;
          -  Active infection (any infection requiring systemic treatment). Hepatitis B or C&#xD;
             [HBV/HCV] is allowed&#xD;
&#xD;
          -  Participants with CNS metastases are not eligible, unless they have completed local&#xD;
             therapy (eg, whole brain radiation therapy [WBRT], surgery or radiosurgery) and have&#xD;
             discontinued the use of corticosteroids for this indication for at least 4 weeks&#xD;
             before starting treatment in this study. Any signs (eg, radiologic) or symptoms of&#xD;
             brain metastases must be stable for at least 4 weeks before starting study treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>California Pacific Medical Center (CPMC)</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ronald Reagan UCLA Medical Center</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mercy Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BRCR Global Texas</name>
      <address>
        <city>Edinburg</city>
        <state>Texas</state>
        <zip>78539</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Haut-Levêque Centre médico-chirurgical Magellan</name>
      <address>
        <city>Pessac</city>
        <state>Bordeaux</state>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Eugène Marquis de Rennes</name>
      <address>
        <city>Rennes</city>
        <state>Brittany</state>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Toulouse</name>
      <address>
        <city>Toulouse</city>
        <state>Occitanie</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Timone</name>
      <address>
        <city>Marseille</city>
        <state>Provence-Alpes-Côte d'Azur</state>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Clinico Humanitas</name>
      <address>
        <city>Milan</city>
        <state>Lombardy</state>
        <zip>20089</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi</name>
      <address>
        <city>Bologna</city>
        <state>Province Of Bologna</state>
        <zip>15-40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 2</name>
      <address>
        <city>Kashiwa</city>
        <state>Chiba</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 4</name>
      <address>
        <city>Kawasaki</city>
        <state>Kanagawa</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 3</name>
      <address>
        <city>Sayama</city>
        <state>Osaka</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Eisai Trial Site 1</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Clinical Oncology Dispensary</name>
      <address>
        <city>Ufa</city>
        <state>Bashkortostan</state>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg City Clinical Oncology Dispansery</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Leningrad Oblast</state>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>S.I. Russian Oncological Research Center n.a. N. N. Blokhin RAMS</name>
      <address>
        <city>Moscow</city>
        <state>Moscow Oblast</state>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altay Regional Oncology Dispensary</name>
      <address>
        <city>Barnaul</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Marqués de Valdecilla</name>
      <address>
        <city>Santander</city>
        <state>Cantabria</state>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañón</name>
      <address>
        <city>Madrid</city>
        <state>Community Of Madrid</state>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <state>Community Of Madrid</state>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Infanta Cristina de Badajoz</name>
      <address>
        <city>Badajoz</city>
        <state>Province Of Badajoz</state>
        <zip>06080</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <state>Province Of Salamanca</state>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Free Hospital</name>
      <address>
        <city>London</city>
        <state>Greater London</state>
        <zip>NW3 2QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <verification_date>August 2022</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>October 22, 2020</results_first_submitted>
  <results_first_submitted_qc>December 7, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">December 31, 2020</results_first_posted>
  <last_update_submitted>January 13, 2023</last_update_submitted>
  <last_update_submitted_qc>January 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 17, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>hepatocellular carcinoma</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>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</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>January 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT03006926/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 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/26/NCT03006926/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 24 investigative sites in the United States, Japan, United Kingdom, France, Italy, Spain, and Russian Federation. Results in this summary are reported based on the primary completion date (31 October 2019) of study.</recruitment_details>
      <pre_assignment_details>A total of 104 participants were enrolled and received treatment. Of these, 6 participants were enrolled in DLT part and 98 were enrolled in the expansion part.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>DLT Part: Lenvatinib 12 mg or 8 mg + Pembrolizumab 200 mg</title>
          <description>In DLT part, participants received lenvatinib 12 milligram (mg) or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in Cycle 1 of a 21-day treatment cycle. Participants with body weight greater than or equal to (&gt;=) 60 kilogram (kg) received lenvatinib 12 mg, participants with body weight less than (&lt;) 60 kg, received lenvatinib 8 mg. Participants who discontinued treatment in Cycle 1, entered the follow-up phase. Participants who were still receiving treatment at the end of Cycle 1, continued to receive same treatment until progressive disease (PD), development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Upon confirmation of the tolerability of the tested combination regimen of lenvatinib plus pembrolizumab in in Cycle 1, expansion part was opened for participant's enrollment.</description>
        </group>
        <group group_id="P2">
          <title>Expansion Part: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
          <description>In the Expansion part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</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 group_id="P2" count="98"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="98"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="33"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing Survival Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Ongoing-on Treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The efficacy analysis set included all participants who had received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>DLT Part: Lenvatinib 12 mg or 8 mg + Pembrolizumab 200 mg</title>
          <description>In DLT part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in Cycle 1 of a 21-day treatment cycle. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg. Participants who discontinued treatment in Cycle 1, entered the follow-up phase. Participants who were still receiving treatment at the end of Cycle 1, continued to receive same treatment until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Upon confirmation of the tolerability of the tested combination regimen of lenvatinib plus pembrolizumab in in Cycle 1, expansion part was opened for participant's enrolment.</description>
        </group>
        <group group_id="B2">
          <title>Expansion Part: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
          <description>In the Expansion part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="98"/>
            <count group_id="B3" value="104"/>
          </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="65.2" spread="10.11"/>
                    <measurement group_id="B2" value="66.2" spread="8.16"/>
                    <measurement group_id="B3" value="66.1" spread="8.23"/>
                  </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="1"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="79"/>
                    <measurement group_id="B3" value="84"/>
                  </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 group_id="B2" value="3"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="78"/>
                    <measurement group_id="B3" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="51"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
        <time_frame>From first dose until 30 days after the last dose (up to approximately 2 years 9 months)</time_frame>
        <population>The safety analysis set included all participants who had received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>DLT Part: Lenvatinib 12 mg or 8 mg + Pembrolizumab 200 mg</title>
            <description>In DLT part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in Cycle 1 of a 21-day treatment cycle. Participants with Body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg. Participants who discontinued treatment in Cycle 1, entered the follow up phase. Participants who were still receiving treatment at the end of Cycle 1, continued to receive same treatment until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
          <population>The safety analysis set included all participants who had 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="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Expansion Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
        <time_frame>From first dose until 30 days after the last dose (up to approximately 2 years 9 months)</time_frame>
        <population>The safety analysis set included all participants who had received at least 1 dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Expansion Part: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>In the Expansion part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, in 21-day treatment cycles until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>Expansion Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
          <population>The safety analysis set included all participants who had 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="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>DLT Part: Number of Participants With Dose Limiting Toxicities (DLTs)</title>
        <description>DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following: (1) any of the hematological or nonhematological toxicities considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; (2) failure to &gt;=75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; (3) participants who discontinue treatment due to treatment-related toxicity in Cycle 1; (4) &gt;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>From first dose of study drug up to Cycle 1 Day 21 (Cycle length= 21 days)</time_frame>
        <population>The DLT analysis set included all participants (except for the Expansion part) who had completed Cycle 1 without major protocol deviation with at least 75% of study drug compliance and assessed for DLT, and participants who had experienced DLT during Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>DLT Part: Lenvatinib 12 mg or 8 mg + Pembrolizumab 200 mg</title>
            <description>In DLT part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in Cycle 1 of a 21-day treatment cycle. Participants with Body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg. Participants who discontinued treatment in Cycle 1, entered the follow up phase. Participants who were still receiving treatment at the end of Cycle 1, continued to receive same treatment until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT Part: Number of Participants With Dose Limiting Toxicities (DLTs)</title>
          <description>DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following: (1) any of the hematological or nonhematological toxicities considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; (2) failure to &gt;=75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; (3) participants who discontinue treatment due to treatment-related toxicity in Cycle 1; (4) &gt;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 analysis set included all participants (except for the Expansion part) who had completed Cycle 1 without major protocol deviation with at least 75% of study drug compliance and assessed for DLT, and participants who had 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>Primary</type>
        <title>DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST and RECIST 1.1 Assessed by Independent Imaging Review (IIR)</title>
        <description>ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by IIR analysis. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 millimeter [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the long diameter (LD) (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.</description>
        <time_frame>From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
        <population>All participants with hepatocellular carcinoma (HCC) who had received at least 1 dose of combination of lenvatinib and pembrolizumab,as first line (1L) therapy, with no prior systemic therapy. In DLT part, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST and RECIST 1.1 Assessed by Independent Imaging Review (IIR)</title>
          <description>ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by IIR analysis. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 millimeter [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the long diameter (LD) (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.</description>
          <population>All participants with hepatocellular carcinoma (HCC) who had received at least 1 dose of combination of lenvatinib and pembrolizumab,as first line (1L) therapy, with no prior systemic therapy. In DLT part, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis for this measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>RECIST 1.1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.0" lower_limit="26.6" upper_limit="46.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRECIST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.0" lower_limit="36.0" upper_limit="56.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by IIR</title>
        <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on mRECIST assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
        <time_frame>From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
        <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by IIR</title>
          <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on mRECIST assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
          <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</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="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6" lower_limit="6.9" upper_limit="NA">Upper limit of confidence interval could not be estimated due to an insufficient number of events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>DLT+Expansion Part: Duration of Response (DOR) Based on RECIST 1.1 Assessed by IIR</title>
        <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
        <time_frame>From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
        <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Duration of Response (DOR) Based on RECIST 1.1 Assessed by IIR</title>
          <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
          <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</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="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.6" lower_limit="6.9" upper_limit="NA">Upper limit of confidence interval could not be estimated due to an insufficient number of events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST Assessed by Investigator Review</title>
        <description>ORR was defined as the percentage of participants who had BOR of CR or PR based on mRECIST assessed by investigator review. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
        <time_frame>From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
        <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab, as first line therapy, with no prior systemic therapy. In DLT part of the study, 4 participants had received prior sorafenib, therefore, they were excluded from analysis for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC 1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST Assessed by Investigator Review</title>
          <description>ORR was defined as the percentage of participants who had BOR of CR or PR based on mRECIST assessed by investigator review. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
          <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab, as first line therapy, with no prior systemic therapy. In DLT part of the study, 4 participants had received prior sorafenib, therefore, they were excluded from analysis for this measure.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.0" lower_limit="31.3" upper_limit="51.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by Investigator Review</title>
        <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) based on mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
        <time_frame>From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)</time_frame>
        <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab,as first line therapy,with no prior systemic therapy. In DLT part of study, 4 participants had received prior sorafenib, therefore, they were excluded. &quot;Overall Number of Participants Analyzed&quot;: participants evaluable for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by Investigator Review</title>
          <description>DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) based on mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
          <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab,as first line therapy,with no prior systemic therapy. In DLT part of study, 4 participants had received prior sorafenib, therefore, they were excluded. &quot;Overall Number of Participants Analyzed&quot;: participants evaluable for this measure.</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="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.6" lower_limit="6.2" upper_limit="18.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Progression-free Survival (PFS) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review</title>
        <description>PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on mRECIST and RECIST 1.1 assessed by IIR, and mRECIST assessed by investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
        <time_frame>From the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) (up to approximately 2 years 9 months)</time_frame>
        <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab,as first line therapy, with no prior systemic therapy. In DLT part of the study, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Progression-free Survival (PFS) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review</title>
          <description>PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on mRECIST and RECIST 1.1 assessed by IIR, and mRECIST assessed by investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
          <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab,as first line therapy, with no prior systemic therapy. In DLT part of the study, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis for this measure.</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="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>mRECIST: IIR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.3" lower_limit="5.6" upper_limit="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RECIST 1.1: IIR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6" lower_limit="7.1" upper_limit="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRECIST: Investigator Review</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.2" lower_limit="7.4" upper_limit="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Time-to Progression (TTP) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review</title>
        <description>TTP was defined as the time from the first study dose date to the date of first documentation of PD, based on mRECIST and RECIST 1.1 assessed by IIR and mRECIST assessed by an investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
        <time_frame>From date of first dose of study drug until disease progression (up to approximately 2 years 9 months)</time_frame>
        <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab, as first line therapy, with no prior systemic therapy. In DLT part of the study, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis of this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Time-to Progression (TTP) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review</title>
          <description>TTP was defined as the time from the first study dose date to the date of first documentation of PD, based on mRECIST and RECIST 1.1 assessed by IIR and mRECIST assessed by an investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).</description>
          <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab, as first line therapy, with no prior systemic therapy. In DLT part of the study, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis of this measure.</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="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>mRECIST: IIR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.7" lower_limit="7.9" upper_limit="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RECIST 1.1: IIR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.7" lower_limit="7.7" upper_limit="13.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>mRECIST: Investigator Review</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.7" lower_limit="7.7" upper_limit="13.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by IIR</title>
        <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
        <time_frame>From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)</time_frame>
        <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by IIR</title>
          <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
          <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.9" lower_limit="1.2" upper_limit="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Time-to Response (TTR) Based on RECIST 1.1 Assessed by IIR</title>
        <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to RECIST 1.1 assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
        <time_frame>From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)</time_frame>
        <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Time-to Response (TTR) Based on RECIST 1.1 Assessed by IIR</title>
          <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to RECIST 1.1 assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
          <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.8" lower_limit="1.2" upper_limit="7.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by Investigator Review</title>
        <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
        <time_frame>From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)</time_frame>
        <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by Investigator Review</title>
          <description>TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is &lt;10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.</description>
          <population>All participants with HCC who received at least 1 dose of combination of lenvatinib and pembrolizumab as 1L therapy with no prior systemic therapy. In DLT part, 4 participants who received prior systemic therapy with sorafenib, were excluded from analysis for this measure. Overall number analyzed are the participants who were evaluable for this outcome measure.</population>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="41"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.7" lower_limit="1.2" upper_limit="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>DLT+Expansion Part: Overall Survival (OS)</title>
        <description>OS was measured from the date of first dose of study drug until date of death from any cause. Participants who were lost to follow-up and the participants who were alive at the date of data cutoff was censored at the date the participant was last known alive, whichever came earlier.</description>
        <time_frame>From the date of first dose of study drug until date of death from any cause (up to approximately 2 years 9 months)</time_frame>
        <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab, as first line therapy, with no prior systemic therapy. In DLT part of study, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis of this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>HCC-1L: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
            <description>Participants received lenvatinib 8 or 12 mg, capsules, orally, once daily in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles as first line therapy until disease progression, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</description>
          </group>
        </group_list>
        <measure>
          <title>DLT+Expansion Part: Overall Survival (OS)</title>
          <description>OS was measured from the date of first dose of study drug until date of death from any cause. Participants who were lost to follow-up and the participants who were alive at the date of data cutoff was censored at the date the participant was last known alive, whichever came earlier.</description>
          <population>All participants with HCC who had received at least 1 dose of combination of lenvatinib and pembrolizumab, as first line therapy, with no prior systemic therapy. In DLT part of study, 4 participants had received prior systemic therapy with sorafenib, therefore, they were excluded from analysis of this measure.</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="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.0" lower_limit="20.4" upper_limit="NA">Upper limit of confidence interval could not be estimated due to an insufficient number of events.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax: Maximum Observed Plasma Concentration for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time to Reach the Cmax for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-ti): Area Under The Plasma Concentration-time Curve From Zero (Pre-Dose) to a Given Sampling Time (ti) for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>t1/2: Terminal Elimination Phase Half-Life for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CL/F: Apparent Total Clearance for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Vz/F: Apparent Volume of Distribution at Terminal Phase for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tss,Max: Time to Maximum Concentration at Steady State For Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clss/F: Apparent Total Clearance Following Oral Administration at Steady State for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Css,Av: Average Steady State Plasma Concentration for Lenvatinib and Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rac (Cmax): Accumulation Index of Cmax for Lenvatinib and 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. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rac (AUC): Accumulation Index of AUC for Lenvatinib and 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. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab</title>
        <description>Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).</description>
        <time_frame>Cycles 1 and 6 Day 1: Pre-dose (cycle length=21 days)</time_frame>
        <posting_date>11/2023</posting_date>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the date of administration of the first dose of the study drug up to 30 days after the last dose of study drug (up to approximately 2 years 9 months)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>DLT Part: Lenvatinib 12 mg or 8 mg + Pembrolizumab 200 mg</title>
          <description>In DLT part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in Cycle 1 of a 21-day treatment cycle. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg. Participants who discontinued treatment in Cycle 1, entered the follow-up phase. Participants who were still receiving treatment at the end of Cycle 1, continued to receive same treatment until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Upon confirmation of the tolerability of the tested combination regimen of lenvatinib plus pembrolizumab in in Cycle 1, expansion part was opened for participant's enrolment.</description>
        </group>
        <group group_id="E2">
          <title>Expansion Part: Lenvatinib 12 mg or 8 mg+ Pembrolizumab 200 mg</title>
          <description>In the Expansion part, participants received lenvatinib 12 mg or 8 mg capsules, orally, once daily, in combination with pembrolizumab 200 mg, infusion, intravenously, every 3 weeks, in 21-day treatment cycles until PD, development of unacceptable toxicity, withdrawal of consent, or study termination by sponsor. Participants with body weight &gt;=60 kg received lenvatinib 12 mg, participants with body weight &lt;60 kg, received lenvatinib 8 mg.</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="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="64" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pancytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hypophysitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Oesophageal varices haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Immune-mediated pancreatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Intestinal perforation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Intra-abdominal fluid collection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Odynophagia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pancreatitis acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Biliary colic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hepatic pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Immune-mediated hepatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Jaundice cholestatic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Liver disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Portal vein thrombosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Biliary sepsis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Clostridium difficile infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Peritonitis bacterial</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Staphylococcal bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="12" subjects_affected="8" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hyperammonaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Acute lymphocytic leukaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Metastases to central nervous system</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Oesophageal squamous cell carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pancreatic carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Facial paralysis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Renal impairment</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Urinary retention</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Acquired hydrocele</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Prostatic obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Immune-mediated pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema multiforme</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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"/>
                <counts group_id="E2" subjects_affected="97" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="41" subjects_affected="19" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="14" subjects_affected="7" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="13" subjects_affected="8" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="34" subjects_affected="29" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="25" subjects_affected="17" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="9" subjects_affected="7" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="14" subjects_affected="13" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Dental caries</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="15" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E2" events="103" subjects_affected="48" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="31" subjects_affected="21" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="26" subjects_affected="14" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="28" subjects_affected="18" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="49" subjects_affected="24" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="59" subjects_affected="32" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="16" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="20" subjects_affected="14" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="15" subjects_affected="10" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperbilirubinaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="24" subjects_affected="8" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Contrast media allergy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Contrast media reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="10" subjects_affected="8" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="3" subjects_affected="1" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="36" subjects_affected="19" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="25" subjects_affected="11" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="9" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="70" subjects_affected="30" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood albumin decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="19" subjects_affected="11" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="51" subjects_affected="19" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="12" subjects_affected="10" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood thyroid stimulating hormone increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="10" subjects_affected="6" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="10" subjects_affected="6" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Eosinophil count increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="16" subjects_affected="9" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="44" subjects_affected="20" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="17" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" events="39" subjects_affected="6" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="38" subjects_affected="12" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="13" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="58" subjects_affected="28" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="39" subjects_affected="7" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="15" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" events="65" subjects_affected="34" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="43" subjects_affected="12" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="17" subjects_affected="6" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="43" subjects_affected="14" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="20" subjects_affected="12" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="18" subjects_affected="13" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="13" subjects_affected="8" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="20" subjects_affected="15" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Groin pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="7" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="9" subjects_affected="6" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="11" subjects_affected="8" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="10" subjects_affected="9" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Hepatic encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="5" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="8" subjects_affected="7" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="13" subjects_affected="8" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" events="16" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="54" subjects_affected="24" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="5" subjects_affected="4" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="29" subjects_affected="22" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="11" subjects_affected="7" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis bullous</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="38" subjects_affected="22" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="20" subjects_affected="17" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="6" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" events="24" subjects_affected="16" subjects_at_risk="98"/>
              </event>
              <event>
                <sub_title>Skin erosion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="17" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E2" events="85" subjects_affected="37" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Inquiry Service</name_or_title>
      <organization>Eisai Co., Ltd.</organization>
      <email>eisai-chiken_hotline@hhc.eisai.co.jp</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03006926
org study id: E7080-J081-116
secondary id: KEYNOTE 524
secondary id: 2018-000522-55
nct id: NCT03006926
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label Phase 1b study designed to evaluate the tolerability and safety of
      lenvatinib in combination with pembrolizumab in participants with hepatocellular carcinoma
      (HCC). The study will evaluate objective response rate and duration of response by modified
      Response Evaluation Criteria In Solid Tumors (mRECIST) for HCC and Response Evaluation
      Criteria In Solid Tumors (RECIST 1.1) based on independent imaging review (IIR).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: From first dose until 30 days after the last dose (up to approximately 2 years 9 months)
measure: Expansion Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: From first dose until 30 days after the last dose (up to approximately 2 years 9 months)
measure: DLT Part: Number of Participants With Dose Limiting Toxicities (DLTs)
time frame: From first dose of study drug up to Cycle 1 Day 21 (Cycle length= 21 days)
description: DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following: (1) any of the hematological or nonhematological toxicities considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; (2) failure to >=75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; (3) participants who discontinue treatment due to treatment-related toxicity in Cycle 1; (4) >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: DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST and RECIST 1.1 Assessed by Independent Imaging Review (IIR)
time frame: From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)
description: ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by IIR analysis. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 millimeter [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the long diameter (LD) (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.
measure: DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by IIR
time frame: From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)
description: DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on mRECIST assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
measure: DLT+Expansion Part: Duration of Response (DOR) Based on RECIST 1.1 Assessed by IIR
time frame: From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)
description: DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
measure: DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST Assessed by Investigator Review
time frame: From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)
description: ORR was defined as the percentage of participants who had BOR of CR or PR based on mRECIST assessed by investigator review. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.
measure: DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by Investigator Review
time frame: From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)
description: DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) based on mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
measure: DLT+Expansion Part: Progression-free Survival (PFS) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review
time frame: From the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) (up to approximately 2 years 9 months)
description: PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on mRECIST and RECIST 1.1 assessed by IIR, and mRECIST assessed by investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
measure: DLT+Expansion Part: Time-to Progression (TTP) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review
time frame: From date of first dose of study drug until disease progression (up to approximately 2 years 9 months)
description: TTP was defined as the time from the first study dose date to the date of first documentation of PD, based on mRECIST and RECIST 1.1 assessed by IIR and mRECIST assessed by an investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).
measure: DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by IIR
time frame: From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)
description: TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.
measure: DLT+Expansion Part: Time-to Response (TTR) Based on RECIST 1.1 Assessed by IIR
time frame: From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)
description: TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to RECIST 1.1 assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.
measure: DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by Investigator Review
time frame: From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)
description: TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.
measure: DLT+Expansion Part: Overall Survival (OS)
time frame: From the date of first dose of study drug until date of death from any cause (up to approximately 2 years 9 months)
description: OS was measured from the date of first dose of study drug until date of death from any cause. Participants who were lost to follow-up and the participants who were alive at the date of data cutoff was censored at the date the participant was last known alive, whichever came earlier.
measure: Cmax: Maximum Observed Plasma Concentration for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Tmax: Time to Reach the Cmax for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: AUC(0-ti): Area Under The Plasma Concentration-time Curve From Zero (Pre-Dose) to a Given Sampling Time (ti) for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: t1/2: Terminal Elimination Phase Half-Life for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: CL/F: Apparent Total Clearance for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Vz/F: Apparent Volume of Distribution at Terminal Phase for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Tss,Max: Time to Maximum Concentration at Steady State For Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Clss/F: Apparent Total Clearance Following Oral Administration at Steady State for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Css,Av: Average Steady State Plasma Concentration for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Rac (Cmax): Accumulation Index of Cmax for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
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. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Rac (AUC): Accumulation Index of AUC for Lenvatinib and Pembrolizumab
time frame: Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)
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. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
measure: Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab
time frame: Cycles 1 and 6 Day 1: Pre-dose (cycle length=21 days)
description: Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).
arm group label: lenvatinib 8 or 12 mg plus pembrolizumab 200 mg
arm group type: Experimental
description: Participants will receive oral lenvatinib at a starting dose of 8 or 12 milligrams (mg) once a day (QD) in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle. The starting dose of lenvatinib will be based on Baseline body weight. Participants weighing greater than or equal to 60 kilograms (kg) will receive 12 mg QD; participants weighing less than 60 kg will receive 8 mg QD.
intervention type: Drug
intervention name: lenvatinib
description: 4 mg capsules
arm group label: lenvatinib 8 or 12 mg plus pembrolizumab 200 mg
intervention type: Drug
intervention name: pembrolizumab (200 mg)
description: 30-minute intravenous infusion
arm group label: lenvatinib 8 or 12 mg plus pembrolizumab 200 mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
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country: France
country: Italy
country: Japan
country: Russian Federation
country: Spain
country: United Kingdom
country: United States
country: Germany
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
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: 