<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/NCT01668017</url>
  </required_header>
  <id_info>
    <org_study_id>EMR 200066-010</org_study_id>
    <nct_id>NCT01668017</nct_id>
  </id_info>
  <brief_title>A Multicentre, Open Label, Phase 1 Trial in Japan of the Mitogen Activated Protein Extracellular Signal Regulated Kinase (MEK) Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy</brief_title>
  <official_title>A Multicentre, Open Label, Phase I Trial in Japan of the MEK Inhibitor Pimasertib Given Orally to Subjects With Solid Tumors as Monotherapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Serono Co., Ltd., Japan</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Merck KGaA, Darmstadt, Germany</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a two-part trial. &quot;Solid tumor&quot; in this protocol means solid tumor excluding&#xD;
      hepatocellular carcinoma (HCC).&#xD;
&#xD;
      Part 1: Dose Escalation Phase in subjects with solid tumor (Cohort A) and HCC (Cohort B). The&#xD;
      dose will be increased from 45 mg twice a day (BID) with 3+3 cohort method up to the&#xD;
      recommended phase 2 dose (RP2D) of pimasertib established as single agent in the global&#xD;
      studies for each arm independently.&#xD;
&#xD;
      Part 2: The Maximum Tolerated Dose (MTD) defined in Part 1 will be confirmed in more subjects&#xD;
      in Cohort A (N=18) and Cohort B (N=6) separately.&#xD;
&#xD;
      Following the recommendation by the Safety Monitoring Committee, Cohort B was discontinued&#xD;
      due to hepatocellular carcinoma (HCC) and there will be no further enrollment of subjects to&#xD;
      this cohort. This decision is based upon review of safety and efficacy information.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The sponsor decided not to conduct the expansion part of trial (part 2)&#xD;
  </why_stopped>
  <start_date type="Actual">September 30, 2012</start_date>
  <completion_date type="Actual">May 31, 2015</completion_date>
  <primary_completion_date type="Actual">May 31, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Subjects Who Experienced at Least One Dose Limiting Toxicity (DLT)</measure>
    <time_frame>During Treatment Cycle 1 (Day 1 to 21)</time_frame>
    <description>DLT defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0): any of following toxicities possibly/probably related to study drug: Any non-hematological toxicity of Grade 3 or higher (excluding Grade 3 asymptomatic rise in liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT] reversible in 7 days for subjects with solid tumor and without liver involvement, or Grade 4 for subjects with HCC or with liver involvement; Grade 3 or 4 asymptomatic rise in creatinine phosphokinase (CPK) reversible in 7 days, deniable for myocardial infarction and rhabdomyolysis; Grade 3 vomiting/diarrhea encountered without optimal therapy). Any Grade 4 neutropenia &gt;5 days duration, any Grade 3 or above febrile neutropenia. Grade 4 thrombocytopenia &gt;1 day or Grade 3 with bleeding. Any treatment delay &gt;2 weeks due to drug-related adverse effects.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs</measure>
    <time_frame>Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks</time_frame>
    <description>An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Data were not reported for &quot;Part 1: Pimasertib 45 mg in HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration Over Time (AUCt) at Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration Over Time (AUCt) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib of 1 Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/f) of Pimasertib on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance (CL/f) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance at Steady-state (CLss/f) of Pimasertib on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Clearance at Steady-state (CLss/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution at Terminal Phase (Vz/f) Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
    <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
    <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio for AUC Racc(AUC) of Pimasertib</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
    <description>Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio for AUC Racc(AUC) of Part 1: Pimasertib 30 mg In HCC Arm</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
    <description>Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio for Cmax Racc(Cmax) of Pimasertib</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
    <description>Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax). Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation Ratio for Cmax Racc(Cmax) of Part 1: Pimasertib 30 mg In HCC Arm</measure>
    <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
    <description>Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Best Overall Response</measure>
    <time_frame>Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)</time_frame>
    <description>Percentage of subjects with best overall response in each category (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Objective Response</measure>
    <time_frame>Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)</time_frame>
    <description>Percentage of subjects with objective response (CR plus PR) according to RECIST Version 1.1 was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Subjects With Disease Control</measure>
    <time_frame>Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)</time_frame>
    <description>Percentage of subjects with disease control (CR plus PR plus greater than 12 weeks SD) according to RECIST Version 1.1 was reported CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <condition>Hepatocellular Carcinoma</condition>
  <arm_group>
    <arm_group_label>Part 1: Pimasertib 30mg in Solid Tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Pimasertib 45 mg in Solid Tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Pimasertib 60 mg in Solid Tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Pimasertib 30 mg in Hepatocellular Carcinoma (HCC)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Pimasertib 45 mg in HCC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimasertib</intervention_name>
    <description>Subjects with solid tumor will be administered with Pimasertib 30 mg twice a day (BID) in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
    <arm_group_label>Part 1: Pimasertib 30mg in Solid Tumor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimasertib</intervention_name>
    <description>Subjects with solid tumor will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
    <arm_group_label>Part 1: Pimasertib 45 mg in Solid Tumor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimasertib</intervention_name>
    <description>Subjects with solid tumor will be administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
    <arm_group_label>Part 1: Pimasertib 60 mg in Solid Tumor</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimasertib</intervention_name>
    <description>Subjects with HCC will be administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
    <arm_group_label>Part 1: Pimasertib 30 mg in Hepatocellular Carcinoma (HCC)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pimasertib</intervention_name>
    <description>Subjects with HCC will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
    <arm_group_label>Part 1: Pimasertib 45 mg in HCC</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Cohort A: A histologically or cytologically confirmed diagnosis of advanced solid tumors&#xD;
        which is either refractory after standard therapy for the disease or for which no effective&#xD;
        standard therapy is available. Archived tumor tissue available or biopsy of tumor tissue&#xD;
        needs to be performed.&#xD;
&#xD;
        Cohort B: A histologically or cytologically confirmed diagnosis of advanced hepatocellular&#xD;
        carcinoma (HCC) which is either refractory after standard therapy for the disease or for&#xD;
        which no effective standard therapy is available. Archived tumor tissue available or biopsy&#xD;
        of tumor tissue needs to be performed. Subjects with Child Pugh A.&#xD;
&#xD;
          -  Male or female Japanese, age greater than or equal to (&gt;=) 18 years.&#xD;
&#xD;
          -  Subject has read and understands the informed consent form and is willing and able to&#xD;
             give informed consent. The subject fully understands requirements of the trial and is&#xD;
             willing to comply with all trial visits and assessments.&#xD;
&#xD;
          -  Women of childbearing potential must have a negative blood pregnancy test at the&#xD;
             screening visit.&#xD;
&#xD;
          -  Female subjects of childbearing potential and male subjects with female partners of&#xD;
             childbearing potential must be willing to avoid pregnancy by using an adequate method&#xD;
             of contraception for 2 weeks prior to, during and four weeks after the last dose&#xD;
             investigational medicinal product (IMP).&#xD;
&#xD;
          -  Life expectancy of at least 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Hematological abnormality Cohort A: Hematological test abnormalities of Hemoglobin &lt; 9.0&#xD;
        g/dL, Neutrophil count &lt; 1.0*10^9/L and Platelet count &lt; 100*10^9/L.&#xD;
&#xD;
        Cohort B: Hematological test abnormalities of Hemoglobin &lt; 9.0 g/dL, Neutrophil count &lt;&#xD;
        1.0*10^9/L, Platelet count &lt; 75*10^9/L, subjects with hepatic encephalopathy&#xD;
&#xD;
          -  Renal impairment as evidenced by serum creatinine &gt; 1.5*upper limit of normal (ULN),&#xD;
             and calculated creatinine clearance &lt; 60 mL/min by Cockcroft-Gault formula.&#xD;
&#xD;
          -  Liver function abnormality of Total Bilirubin &gt; 1.5*ULN, or aspartate transaminase&#xD;
             9AST) or alkaline phosphatase (ALT)&gt; 2.5*ULN. For subjects with HCC or liver&#xD;
             involvement AST/ALT &gt; 5*ULN.&#xD;
&#xD;
          -  History of central nervous system (CNS) metastases, unless subject has been previously&#xD;
             treated for CNS metastases&#xD;
&#xD;
          -  History of difficulty swallowing, malabsorption or other chronic gastro-intestinal&#xD;
             disease or conditions&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group Performance status (ECOG PS) greater than 1.&#xD;
&#xD;
          -  Has received chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any&#xD;
             other anticancer therapy (including any investigational agent) or surgical&#xD;
             intervention within 28 days or 5 half lives for non-cytotoxics of registration.&#xD;
&#xD;
          -  Baseline corrected QT interval on screening ECG (QTc) &gt;= 480 ms or left ventricular&#xD;
             ejection fraction (LVEF) &lt; 40% on screening echocardiogram&#xD;
&#xD;
          -  Cohort B: Subjects with hepatic encephalopathy, remarkable ascites and subjects with&#xD;
             history of esophageal varices rupture within 6 months (subjects with symptom&#xD;
             improvement after treatment are eligible)&#xD;
&#xD;
          -  Other serious illness or medical conditions.&#xD;
&#xD;
          -  Retinal degenerative disease.&#xD;
&#xD;
          -  Previous treatment with MEK inhibitors.&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck Serono Co., Ltd., Tokyo, an affiliate of Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Please contact</name>
      <address>
        <city>Merck Serono Co., Ltd for recruiting locations in</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <results_first_submitted>February 12, 2017</results_first_submitted>
  <results_first_submitted_qc>February 12, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">March 29, 2017</results_first_posted>
  <last_update_submitted>July 19, 2017</last_update_submitted>
  <last_update_submitted_qc>July 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Advanced solid tumors</keyword>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>cancer, liver</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Niacinamide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>First/last subject (informed consent): September 2012/April 2015. Last subject completed: April 2015.</recruitment_details>
      <pre_assignment_details>This study was to be conducted in 2 parts; Part 1 was the dose escalation phase and Part 2 was the expansion phase. However, due to early termination of the study, the sponsor decided not to conduct the expansion phase (Part 2).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 30 milligram (mg) twice a day (BID) in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="P2">
          <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="P3">
          <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="P4">
          <title>Part 1: Pimasertib 30 mg in Hepatocellular Carcinoma (HCC)</title>
          <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="P5">
          <title>Part 1: Pimasertib 45 mg in HCC</title>
          <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set included all subjects who received at least one administration of pimasertib.</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21- day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="B2">
          <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="B3">
          <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="B4">
          <title>Part 1: Pimasertib 30 mg in HCC</title>
          <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="B5">
          <title>Part 1: Pimasertib 45 mg in HCC</title>
          <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="B6">
          <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="4"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="2"/>
            <count group_id="B6" value="26"/>
          </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="62.3" spread="12.20"/>
                    <measurement group_id="B2" value="61.4" spread="10.63"/>
                    <measurement group_id="B3" value="61.5" spread="9.29"/>
                    <measurement group_id="B4" value="58.8" spread="13.63"/>
                    <measurement group_id="B5" value="56.5" spread="20.51"/>
                    <measurement group_id="B6" value="60.7" spread="11.0"/>
                  </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="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects Who Experienced at Least One Dose Limiting Toxicity (DLT)</title>
        <description>DLT defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0): any of following toxicities possibly/probably related to study drug: Any non-hematological toxicity of Grade 3 or higher (excluding Grade 3 asymptomatic rise in liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT] reversible in 7 days for subjects with solid tumor and without liver involvement, or Grade 4 for subjects with HCC or with liver involvement; Grade 3 or 4 asymptomatic rise in creatinine phosphokinase (CPK) reversible in 7 days, deniable for myocardial infarction and rhabdomyolysis; Grade 3 vomiting/diarrhea encountered without optimal therapy). Any Grade 4 neutropenia &gt;5 days duration, any Grade 3 or above febrile neutropenia. Grade 4 thrombocytopenia &gt;1 day or Grade 3 with bleeding. Any treatment delay &gt;2 weeks due to drug-related adverse effects.</description>
        <time_frame>During Treatment Cycle 1 (Day 1 to 21)</time_frame>
        <population>DLT analysis set included all subjects who experienced any DLT during Cycle 1 and who received above 85% of all planned doses of pimasertib during Cycle 1.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.</description>
          </group>
          <group group_id="O5">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject, whichever comes first.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects Who Experienced at Least One Dose Limiting Toxicity (DLT)</title>
          <description>DLT defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0): any of following toxicities possibly/probably related to study drug: Any non-hematological toxicity of Grade 3 or higher (excluding Grade 3 asymptomatic rise in liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT] reversible in 7 days for subjects with solid tumor and without liver involvement, or Grade 4 for subjects with HCC or with liver involvement; Grade 3 or 4 asymptomatic rise in creatinine phosphokinase (CPK) reversible in 7 days, deniable for myocardial infarction and rhabdomyolysis; Grade 3 vomiting/diarrhea encountered without optimal therapy). Any Grade 4 neutropenia &gt;5 days duration, any Grade 3 or above febrile neutropenia. Grade 4 thrombocytopenia &gt;1 day or Grade 3 with bleeding. Any treatment delay &gt;2 weeks due to drug-related adverse effects.</description>
          <population>DLT analysis set included all subjects who experienced any DLT during Cycle 1 and who received above 85% of all planned doses of pimasertib during Cycle 1.</population>
          <units>subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="3"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs</title>
        <description>An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.</description>
        <time_frame>Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks</time_frame>
        <population>Safety analysis set included all subjects who received at least one administration of pimasertib.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O5">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs</title>
          <description>An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.</description>
          <population>Safety analysis set included all subjects who received at least one administration of pimasertib.</population>
          <units>subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 1</title>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>Pharmacokinetic (PK) analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 1</title>
          <population>Pharmacokinetic (PK) analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>nanogram per milliliter (ng/mL)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="162.4" spread="113.1"/>
                    <measurement group_id="O2" value="222.1" spread="45.2"/>
                    <measurement group_id="O3" value="288.3" spread="52.1"/>
                    <measurement group_id="O4" value="167.6" spread="26.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
        <description>The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
          <description>The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>ng/mL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="225"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="281"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 15</title>
        <description>Data were not reported for &quot;Part 1: Pimasertib 45 mg in HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 15</title>
          <description>Data were not reported for &quot;Part 1: Pimasertib 45 mg in HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="199.5" spread="58.9"/>
                    <measurement group_id="O2" value="231.6" spread="66.1"/>
                    <measurement group_id="O3" value="336.3" spread="30.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
        <description>The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
          <description>The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>ng/mL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="320"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="419"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 1</title>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 1</title>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.450" lower_limit="0.48" upper_limit="4.00"/>
                    <measurement group_id="O2" value="1.480" lower_limit="0.48" upper_limit="7.98"/>
                    <measurement group_id="O3" value="1.710" lower_limit="0.97" upper_limit="2.43"/>
                    <measurement group_id="O4" value="1.000" lower_limit="0.95" upper_limit="2.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
        <description>The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
          <description>The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>hours</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 15</title>
        <description>Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 15</title>
          <description>Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.805" lower_limit="1.00" upper_limit="2.48"/>
                    <measurement group_id="O2" value="1.910" lower_limit="1.00" upper_limit="2.48"/>
                    <measurement group_id="O3" value="2.550" lower_limit="1.50" upper_limit="5.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
        <description>The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
          <description>The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>hours</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration Over Time (AUCt) at Cycle 1 Day 1</title>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration Over Time (AUCt) at Cycle 1 Day 1</title>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="703.0" spread="73.8"/>
                    <measurement group_id="O2" value="862.4" spread="42.8"/>
                    <measurement group_id="O3" value="1626.9" spread="43.6"/>
                    <measurement group_id="O4" value="911.4" spread="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration Over Time (AUCt) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
        <description>The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration Over Time (AUCt) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
          <description>The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>h*ng/mL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1754"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1430"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 1</title>
        <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours).</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 1</title>
          <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours).</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="618.3" spread="86.1"/>
                    <measurement group_id="O2" value="857.4" spread="46.0"/>
                    <measurement group_id="O3" value="1629.3" spread="43.7"/>
                    <measurement group_id="O4" value="911.7" spread="27.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib of 1 Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
        <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib of 1 Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
          <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>h*ng/mL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1761"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1431"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 15</title>
        <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 milligram (mg) twice a day (BID) in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 15</title>
          <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1189.3" spread="73.6"/>
                    <measurement group_id="O2" value="1125.0" spread="62.1"/>
                    <measurement group_id="O3" value="2140.7" spread="37.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
        <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
          <description>Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>h*ng/mL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2250"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1687"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 1</title>
        <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 1</title>
          <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.480" lower_limit="3.43" upper_limit="4.78"/>
                    <measurement group_id="O2" value="3.545" lower_limit="2.77" upper_limit="5.24"/>
                    <measurement group_id="O3" value="3.935" lower_limit="2.71" upper_limit="5.61"/>
                    <measurement group_id="O4" value="4.560" lower_limit="3.27" upper_limit="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
        <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
          <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>hours</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 15</title>
        <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 15</title>
          <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.235" lower_limit="0.775" upper_limit="5.21"/>
                    <measurement group_id="O2" value="4.000" lower_limit="3.13" upper_limit="5.71"/>
                    <measurement group_id="O3" value="5.530" lower_limit="2.92" upper_limit="8.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
        <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
          <description>The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>hours</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance (CL/f) of Pimasertib on Cycle 1 Day 1</title>
        <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with HCC were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance (CL/f) of Pimasertib on Cycle 1 Day 1</title>
          <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>liter/hour (L/h)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.67" spread="80.5"/>
                    <measurement group_id="O2" value="48.17" spread="52.8"/>
                    <measurement group_id="O3" value="32.62" spread="54.6"/>
                    <measurement group_id="O4" value="32.19" spread="27.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance (CL/f) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
        <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance (CL/f) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
          <description>Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>L/h</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance at Steady-state (CLss/f) of Pimasertib on Cycle 1 Day 15</title>
        <description>Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance at Steady-state (CLss/f) of Pimasertib on Cycle 1 Day 15</title>
          <description>Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>L/h</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.24" spread="73.6"/>
                    <measurement group_id="O2" value="40.00" spread="62.1"/>
                    <measurement group_id="O3" value="28.02" spread="37.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Clearance at Steady-state (CLss/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
        <description>Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Clearance at Steady-state (CLss/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
          <description>Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>L/h</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 1</title>
        <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 1</title>
          <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="231.2" spread="71.6"/>
                    <measurement group_id="O2" value="238.1" spread="46.7"/>
                    <measurement group_id="O3" value="169.8" spread="29.7"/>
                    <measurement group_id="O4" value="177.2" spread="15.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
        <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1</title>
          <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>liters</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="187"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 15</title>
        <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 15</title>
          <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="105.0" spread="161.1"/>
                    <measurement group_id="O2" value="233.9" spread="46.4"/>
                    <measurement group_id="O3" value="209.1" spread="10.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
        <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution at Terminal Phase (Vz/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15</title>
          <description>Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>liters</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="297"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio for AUC Racc(AUC) of Pimasertib</title>
        <description>Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio for AUC Racc(AUC) of Pimasertib</title>
          <description>Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15. Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.782" spread="4.2"/>
                    <measurement group_id="O2" value="1.382" spread="30.2"/>
                    <measurement group_id="O3" value="1.311" spread="51.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio for AUC Racc(AUC) of Part 1: Pimasertib 30 mg In HCC Arm</title>
        <description>Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio for AUC Racc(AUC) of Part 1: Pimasertib 30 mg In HCC Arm</title>
          <description>Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15.</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>ratio</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio for Cmax Racc(Cmax) of Pimasertib</title>
        <description>Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax). Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
        <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio for Cmax Racc(Cmax) of Pimasertib</title>
          <description>Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax). Data were not reported for &quot;Part 1: Pimasertib 45 mg In HCC&quot; arm as there were no PK samples collected for this arm.</description>
          <population>PK analysis set. Here &quot;Overall Number of Participants Analyzed&quot; signifies the overall number of subjects who were evaluable for this outcome measure for each arm, respectively.</population>
          <units>ratio</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="6"/>
                <count group_id="O3" value="5"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.227" spread="38.3"/>
                    <measurement group_id="O2" value="0.8281" spread="65.5"/>
                    <measurement group_id="O3" value="1.215" spread="61.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Accumulation Ratio for Cmax Racc(Cmax) of Part 1: Pimasertib 30 mg In HCC Arm</title>
        <description>Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax).</description>
        <time_frame>Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15</time_frame>
        <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Accumulation Ratio for Cmax Racc(Cmax) of Part 1: Pimasertib 30 mg In HCC Arm</title>
          <description>Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax).</description>
          <population>PK analysis set included all subjects who received at least 1 planned dose of pimasertib and who had at least 1 measurable post-dose concentration. Subjects with important protocol deviations or events, which may impact the quality of the PK data were excluded from the PK analysis set.</population>
          <units>ratio</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Subject 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Subject 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Best Overall Response</title>
        <description>Percentage of subjects with best overall response in each category (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.</description>
        <time_frame>Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)</time_frame>
        <population>Efficacy analysis set included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O5">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Best Overall Response</title>
          <description>Percentage of subjects with best overall response in each category (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.</description>
          <population>Efficacy analysis set included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="42.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="14.3"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PD</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66.7"/>
                    <measurement group_id="O2" value="42.9"/>
                    <measurement group_id="O3" value="75.0"/>
                    <measurement group_id="O4" value="75.0"/>
                    <measurement group_id="O5" value="50.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Not evaluable</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="25.0"/>
                    <measurement group_id="O4" value="25.0"/>
                    <measurement group_id="O5" value="50.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Objective Response</title>
        <description>Percentage of subjects with objective response (CR plus PR) according to RECIST Version 1.1 was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)</time_frame>
        <population>Efficacy analysis set' included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg twice a day (BID) until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O5">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Objective Response</title>
          <description>Percentage of subjects with objective response (CR plus PR) according to RECIST Version 1.1 was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Efficacy analysis set' included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="42.9"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Subjects With Disease Control</title>
        <description>Percentage of subjects with disease control (CR plus PR plus greater than 12 weeks SD) according to RECIST Version 1.1 was reported CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions.</description>
        <time_frame>Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)</time_frame>
        <population>Efficacy analysis set included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O2">
            <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O3">
            <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
            <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O4">
            <title>Part 1: Pimasertib 30 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
          <group group_id="O5">
            <title>Part 1: Pimasertib 45 mg in HCC</title>
            <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Subjects With Disease Control</title>
          <description>Percentage of subjects with disease control (CR plus PR plus greater than 12 weeks SD) according to RECIST Version 1.1 was reported CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions.</description>
          <population>Efficacy analysis set included all subjects who received at least one administration of planned dose of pimasertib and who have had at least one efficacy assessment after the first dose.</population>
          <units>percentage of subjects</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="7"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="4"/>
                <count group_id="O5" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="57.1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Part 1: Pimasertib 30 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="E2">
          <title>Part 1: Pimasertib 45 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="E3">
          <title>Part 1: Pimasertib 60 mg in Solid Tumor</title>
          <description>Subjects with solid tumor were administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="E4">
          <title>Part 1: Pimasertib 30 mg in HCC</title>
          <description>Subjects with HCC were administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
        <group group_id="E5">
          <title>Part 1: Pimasertib 45 mg in HCC</title>
          <description>Subjects with HCC were administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Jaundice cholestatic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Liver disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </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" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Non-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="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Pericardia effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Retinal detachment</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Retinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Macular oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Ocular hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Retinal tear</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Macular detachment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Metamorphopsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Visual acuity reduced</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Vitreous floaters</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Cheilitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Haemorrhoidal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Feeling hot</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Contrast media allergy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Frostbite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase MB increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Fibrin D dimer increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Menstruation irregular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pulmonary haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Skin ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="4"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Due to the Sponsor's decision not to pursue the study drug as monotherapy, the Expansion Phase (Part 2) of the study was not conducted.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Merck KGaA Communication Center</name_or_title>
      <organization>Merck Healthcare, a business of Merck KGaA, Darmstadt, Germany</organization>
      <phone>+49-6151-72-5200</phone>
      <email>service@merckgroup.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01668017
org study id: EMR 200066-010
nct id: NCT01668017
lead sponsor: 
collaborator: 
has dmc: Yes
This is a two-part trial. "Solid tumor" in this protocol means solid tumor excluding
      hepatocellular carcinoma (HCC).

      Part 1: Dose Escalation Phase in subjects with solid tumor (Cohort A) and HCC (Cohort B). The
      dose will be increased from 45 mg twice a day (BID) with 3+3 cohort method up to the
      recommended phase 2 dose (RP2D) of pimasertib established as single agent in the global
      studies for each arm independently.

      Part 2: The Maximum Tolerated Dose (MTD) defined in Part 1 will be confirmed in more subjects
      in Cohort A (N=18) and Cohort B (N=6) separately.

      Following the recommendation by the Safety Monitoring Committee, Cohort B was discontinued
      due to hepatocellular carcinoma (HCC) and there will be no further enrollment of subjects to
      this cohort. This decision is based upon review of safety and efficacy information.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Subjects Who Experienced at Least One Dose Limiting Toxicity (DLT)
time frame: During Treatment Cycle 1 (Day 1 to 21)
description: DLT defined using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 3.0 (NCI CTCAE v3.0): any of following toxicities possibly/probably related to study drug: Any non-hematological toxicity of Grade 3 or higher (excluding Grade 3 asymptomatic rise in liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], alkaline phosphatase [ALP], gamma-glutamyl transferase [GGT] reversible in 7 days for subjects with solid tumor and without liver involvement, or Grade 4 for subjects with HCC or with liver involvement; Grade 3 or 4 asymptomatic rise in creatinine phosphokinase (CPK) reversible in 7 days, deniable for myocardial infarction and rhabdomyolysis; Grade 3 vomiting/diarrhea encountered without optimal therapy). Any Grade 4 neutropenia >5 days duration, any Grade 3 or above febrile neutropenia. Grade 4 thrombocytopenia >1 day or Grade 3 with bleeding. Any treatment delay >2 weeks due to drug-related adverse effects.
measure: Number of Subjects Who Experienced Treatment-Emergent Adverse Events (TEAEs) or Serious TEAEs
time frame: Baseline up to 30 days post last dose of study drug; assessed maximum up to 39.4 weeks
description: An adverse event (AE) was defined as any untoward medical occurrence which does not necessarily have a causal relationship with this the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pre-treatment state. TEAEs include both Serious TEAEs and non-serious TEAEs.
measure: Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
measure: Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: The summarized data was not available for this arm therefore individual data was presented.
measure: Maximum Observed Concentration (Cmax) of Pimasertib on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Data were not reported for "Part 1: Pimasertib 45 mg in HCC" arm as there were no PK samples collected for this arm.
measure: Maximum Observed Concentration (Cmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: The summarized data was not available for this arm therefore individual data was presented.
measure: Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
measure: Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: The summarized data was not available for this arm therefore individual data was presented.
measure: Time to Reach Maximum Concentration (Tmax) on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.
measure: Time to Reach Maximum Concentration (Tmax) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: The summarized data was not available for this arm therefore individual data was presented.
measure: Area Under the Concentration Over Time (AUCt) at Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
measure: Area Under the Concentration Over Time (AUCt) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: The summarized data was not available for this arm therefore individual data was presented.
measure: Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours).
measure: Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib of 1 Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.
measure: Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Pimasertib at Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.
measure: Area Under the Concentration-Time Curve From Time Zero up to Time Tau (AUC0-tau) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval (12 hours). The summarized data was not available for this arm therefore individual data was presented.
measure: Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination.
measure: Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.
measure: Apparent Terminal Half-life (t1/2) of Pimasertib on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.
measure: Apparent Terminal Half-life (t1/2) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: The apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50% in the final stage of its elimination. The summarized data was not available for this arm therefore individual data was presented.
measure: Apparent Clearance (CL/f) of Pimasertib on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed.
measure: Apparent Clearance (CL/f) of Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Apparent clearance after oral dose (CL/f) is influenced by the fraction absorbed. The summarized data was not available for this arm therefore individual data was presented.
measure: Apparent Clearance at Steady-state (CLss/f) of Pimasertib on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.
measure: Apparent Clearance at Steady-state (CLss/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Apparent clearance at steady state was reported. Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. The summarized data was not available for this arm therefore individual data was presented.
measure: Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed.
measure: Apparent Volume of Distribution at Terminal Phase (Vz/f) Part 1: Pimasertib 45 mg in HCC Arm on Cycle 1 Day 1
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1
description: Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.
measure: Apparent Volume of Distribution at Terminal Phase (Vz/f) of Pimasertib on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. Apparent volume of distribution after oral dose (Vz/f) was influenced by the fraction absorbed. Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.
measure: Apparent Volume of Distribution at Terminal Phase (Vz/f) of Part 1: Pimasertib 30 mg in HCC Arm on Cycle 1 Day 15
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 15
description: Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired serum concentration of a drug. The summarized data was not available for this arm therefore individual data was presented.
measure: Accumulation Ratio for AUC Racc(AUC) of Pimasertib
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15
description: Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15. Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.
measure: Accumulation Ratio for AUC Racc(AUC) of Part 1: Pimasertib 30 mg In HCC Arm
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15
description: Racc (AUC) was calculated as, area under the curve from time zero to end of dosing interval on Day 1 divided by area under the curve from time zero to end of dosing interval on Day 15.
measure: Accumulation Ratio for Cmax Racc(Cmax) of Pimasertib
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15
description: Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax). Data were not reported for "Part 1: Pimasertib 45 mg In HCC" arm as there were no PK samples collected for this arm.
measure: Accumulation Ratio for Cmax Racc(Cmax) of Part 1: Pimasertib 30 mg In HCC Arm
time frame: Cycle 1: Pre-morning dose, 0.5, 1, 1.5, 2, 2.5, 4, 6, 8, hours post dose, pre-evening dose (Hour 12) at Day 1 and Day 15
description: Racc (Cmax) was calculated as, maximum observed plasma concentration on Day 1 (Cmax) divided by maximum observed plasma concentration on Day 15 (Cmax).
measure: Percentage of Subjects With Best Overall Response
time frame: Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)
description: Percentage of subjects with best overall response in each category (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]) according to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
measure: Percentage of Subjects With Objective Response
time frame: Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)
description: Percentage of subjects with objective response (CR plus PR) according to RECIST Version 1.1 was reported. CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Percentage of Subjects With Disease Control
time frame: Day 1 of Cycle 3 and Day 1 of every alternate until end of treatment (up to a maximum of 35.4 weeks)
description: Percentage of subjects with disease control (CR plus PR plus greater than 12 weeks SD) according to RECIST Version 1.1 was reported CR was defined as disappearance of all target and all non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study) or unequivocal progression of existing non-target lesions.
arm group label: Part 1: Pimasertib 30mg in Solid Tumor
arm group type: Experimental
arm group label: Part 1: Pimasertib 45 mg in Solid Tumor
arm group type: Experimental
arm group label: Part 1: Pimasertib 60 mg in Solid Tumor
arm group type: Experimental
arm group label: Part 1: Pimasertib 30 mg in Hepatocellular Carcinoma (HCC)
arm group type: Experimental
arm group label: Part 1: Pimasertib 45 mg in HCC
arm group type: Experimental
intervention type: Drug
intervention name: Pimasertib
description: Subjects with solid tumor will be administered with Pimasertib 30 mg twice a day (BID) in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
arm group label: Part 1: Pimasertib 30mg in Solid Tumor
intervention type: Drug
intervention name: Pimasertib
description: Subjects with solid tumor will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
arm group label: Part 1: Pimasertib 45 mg in Solid Tumor
intervention type: Drug
intervention name: Pimasertib
description: Subjects with solid tumor will be administered with Pimasertib 60 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
arm group label: Part 1: Pimasertib 60 mg in Solid Tumor
intervention type: Drug
intervention name: Pimasertib
description: Subjects with HCC will be administered with Pimasertib 30 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
arm group label: Part 1: Pimasertib 30 mg in Hepatocellular Carcinoma (HCC)
intervention type: Drug
intervention name: Pimasertib
description: Subjects with HCC will be administered with Pimasertib 45 mg BID in 21-day cycles until disease progression, intolerable toxicity, investigators decision to discontinue treatment or withdrawal of consent by the subject.
arm group label: Part 1: Pimasertib 45 mg in HCC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: Merck Serono Co., Ltd., Tokyo, an affiliate of Merck KGaA, Darmstadt, Germany
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Carcinoma, Hepatocellular
mesh term: Niacinamide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Due to the Sponsor's decision not to pursue the study drug as monotherapy, the Expansion Phase (Part 2) of the study was not conducted.
point of contact: 