<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/NCT03289533</url>
  </required_header>
  <id_info>
    <org_study_id>B9991024</org_study_id>
    <nct_id>NCT03289533</nct_id>
  </id_info>
  <brief_title>A Study Of Avelumab In Combination With Axitinib In Advanced HCC (VEGF Liver 100)</brief_title>
  <official_title>AN OPEN LABEL, SINGLE ARM PHASE 1B STUDY OF AVELUMAB PLUS AXITINIB AS FIRST LINE TREATMENT IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first&#xD;
      line treatment in patients with advanced HCC&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 8, 2017</start_date>
  <completion_date type="Actual">October 25, 2019</completion_date>
  <primary_completion_date type="Actual">August 27, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03</measure>
    <time_frame>From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)</time_frame>
    <description>An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Abnormal Laboratory Parameter Values (Hematology) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 4.03</measure>
    <time_frame>From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)</time_frame>
    <description>As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (&lt;) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= &lt;100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (&gt;) 0 to 2 gram per deciliter(g/dL) above upper limit of normal [ULN]; lymphocyte count decreased: Grade 1= &lt;LLN to 0.8*10^9/L, Grade 2= &lt;0.8*10^9/L to 0.5*10^9/L, Grade 3= &lt;0.5*10^9/L to 0.2*10^9/L ; lymphocyte count increased: Grade 2= &gt;4*10^9/L to 20*10^9/L; neutrophil count decreased: Grade 1= &lt;LLN to 1.5*10^9/L ,Grade 2= &lt;1.5*10^9/L to 1.0*10^9/L; platelet count decreased: Grade 1= &lt;LLN to 75.0*10^9/L, Grade 2= &lt;75.0*10^9/L to 50.0*10^9/L; white blood cell decreased: Grade 1= &lt;LLN to 3*10^9/L, Grade 2= &lt;3*10^9/L to 2*10^9/L.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Participants With Abnormal Laboratory Parameter Values (Chemistry) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version (v) 4.03</measure>
    <time_frame>From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)</time_frame>
    <description>ALT,ALP,AST increased grades(g):g1&gt;ULN-3.0*ULN,g2&gt;3.0-5.0*ULN,g3&gt;5.0-20.0*ULN; blood bilirubin increased:g1&gt;ULN-1.5*ULN, g2&gt;1.5-3.0*ULN, g3&gt;3.0-10.0*ULN; [cholesterol high:g1&gt;ULN-7.75, g2 &gt;7.75-10.34,g4 &gt;12.92]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1&gt;ULN-2.5*ULN, g2&gt;2.5*ULN-5*ULN; Ggt increased g3 &gt;5.0-20.0*ULN; Creatinine increased: g1&gt;ULN-1.5*ULN; [hypoalbuminemia:g1&lt;LLN-30,g2&lt;30-20] grams per liter(g/L);[hyperglycemia:g1&gt; ULN-8.9,g2&gt; 8.9-13.9,g3&gt; 13.9-27.8;hypermagnesemia:g1&gt;ULN-1.23;hypercalcemia:g1&gt;ULN -2.9;hyperkalemia:g1&gt;ULN-5.5,hypernatremia:g1&gt;ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 &gt;3.42-5.7;hypocalcemia:g1&lt;LLN-2.0,hypoglycemia:g1&lt;LLN-3.0, g2&lt;3.0-2.2;hypokalemia:g2&lt;LLN-3.0,g4&lt;2.5,hypomagnesemia:g1&lt;LLN-0.5,hyponatremia:g1&lt;LLN-130, g3&lt;130-120,hypophosphatemia:g1&lt;LLN-0.8,g2&lt;0.8-0.6]mmol/L;lipase increased:g1&gt;ULN-1.5*ULN,g3 &gt;2.0-5.0*ULN;serum amylase increased:g1&gt;ULN-1.5*ULN, g2&gt;1.5-2.0*ULN,g3&gt;2.0-5.0*ULN.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Disease Progression (TTP)</measure>
    <time_frame>From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months)</time_frame>
    <description>TTP as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was define as time (in months) from date of first dose of study drug to date of first documentation of progressive disease (PD) or data censoring date, whichever occurred first. PD was defined as greater than or equal to (&gt;=) 20 percent (%) increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment), with a minimum absolute increase of at least 5 millimeter (mm), or appearance of &gt;=1 new lesions. TTP was analyzed by Kaplan-Meier method. TTP data was censored on the date the last adequate tumor assessment for participants without PD, for participants who start new anti-cancer treatment prior to PD, for participants who died without PD, or for participants with PD after &gt;=2 missing tumor assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)</time_frame>
    <description>PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: &gt;= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of &gt;=5 mm, or appearance of &gt;=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after &gt;=2 missing tumor assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Objective Response (OR)</measure>
    <time_frame>From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months)</time_frame>
    <description>OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;) 10 mm. PR was defined as &gt;=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Disease Control (DC)</measure>
    <time_frame>From first dose of study drug until first documentation of CR or PR or SD or till non-CR/non-PD (maximum up to 20 months)</time_frame>
    <description>Disease control as assessed by investigator according to RECIST v1.1, was defined as participants with CR, PR, stable disease (SD), or non-CR/non-PD. CR: disappearance of all target and non-target lesions and sustained for 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters. SD: 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: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm or appearance of &gt;=1 new lesions. Non-CR/non-PD: Persistence of any non-target lesions and/or tumor marker level above the normal limit at &gt;=8 weeks after date of first dose of study treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Tumor Response (TTR)</measure>
    <time_frame>From first dose of study drug until first documentation of CR or PR (maximum up to 20 months)</time_frame>
    <description>TTR as assessed by investigator according to RECIST v1.1 was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DR)</measure>
    <time_frame>From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)</time_frame>
    <description>DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of &gt;=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after &gt;=2 missing tumor assessments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 21 months)</time_frame>
    <description>OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Serum Concentration of Avelumab</measure>
    <time_frame>Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Plasma Concentration of Axitinib</measure>
    <time_frame>Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-dose Serum Concentration of Avelumab</measure>
    <time_frame>Pre-dose on Day 1 of Cycle 2, 3, 4, 6, 8, 12, 16, 20, 24, 28 (Duration of each cycle=14 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-dose Plasma Concentration of Axitinib</measure>
    <time_frame>Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status</measure>
    <time_frame>Baseline (Day 1)</time_frame>
    <description>PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering &gt;= 1% of the tumor area. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering &lt; 1% of the tumor area.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells</measure>
    <time_frame>From first dose of study drug up to end of treatment (maximum up to 20 months)</time_frame>
    <description>CD8+ cells are the type of T-lymphocytes. Invasive margin is defined as the region on each side of the border between tumor cells. Expression of CD8+ cells in invasive margin, center of tumor cells, total area of tumor cells has been reported as mean percentage of CD8+cells per unit area. Area was measured in millimeter square (mm^2).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells</measure>
    <time_frame>From first dose of study drug up to end of treatment (up to 20 months)</time_frame>
    <description>CD8+ cells are the type of T-lymphocytes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)</measure>
    <time_frame>From first dose of study drug until 30 days after the last dose of study drug (maximum up to 21 months)</time_frame>
    <description>ADA positive was defined as presence of at least one positive ADA sample. nAb positive was defined as presence of at least one positive nAb sample.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Carcinoma, Hepatocellular</condition>
  <arm_group>
    <arm_group_label>Experimental 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Avelumab (MSB0010718C) in combination with axitinib (AG-013736)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Avelumab (MSB0010718C)</intervention_name>
    <description>Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.</description>
    <arm_group_label>Experimental 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Axitinib (AG-013736)</intervention_name>
    <description>Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.</description>
    <arm_group_label>Experimental 1</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of locally advanced or metastatic HCC, obtained by histology/cytology (on a&#xD;
             prior tumor biopsy) or by imaging with serum α-fetoprotein (AFP) ≥400 ng/mL.&#xD;
&#xD;
          -  All patients must provide at least 1 archival tumor specimen. If archival tumor&#xD;
             specimen is no longer available, de novo tumor biopsy will be required during&#xD;
             screening.&#xD;
&#xD;
          -  HCC not amenable to local therapy.&#xD;
&#xD;
          -  Measurable disease according to RECIST v. 1.1.&#xD;
&#xD;
          -  Child Pugh Class A disease.&#xD;
&#xD;
          -  BCLC stage B or C disease.&#xD;
&#xD;
          -  No evidence of uncontrolled hypertension as documented by 2 baseline blood pressure&#xD;
             readings taken at least 1 hour apart.&#xD;
&#xD;
          -  ECOG performance status 0 or 1.&#xD;
&#xD;
          -  Adequate bone marrow function, renal and liver functions&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≥ lower limit of normal (LLN) as assessed by&#xD;
             multigated acquisition (MUGA) scan or echocardiogram (ECHO).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior systemic treatment for advanced HCC, including prior treatment with approved or&#xD;
             investigational drugs.&#xD;
&#xD;
          -  Any prior locoregional therapy within 4 weeks and radiotherapy or surgical procedure&#xD;
             within 2 weeks (4 weeks for major surgery) of enrollment.&#xD;
&#xD;
          -  Patients with known symptomatic brain metastases requiring steroids.&#xD;
&#xD;
          -  Presence of hepatic encephalopathy (ie, Child Pugh score of 2 or 3) and/or clinically&#xD;
             relevant ascites (ie, Child Pugh score of 3).&#xD;
&#xD;
          -  Presence of main portal vein invasion by HCC.&#xD;
&#xD;
          -  Any of the following within the 12 months prior to enrollment: myocardial infarction,&#xD;
             severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic&#xD;
             congestive heart failure, LVEF less than LLN, clinically significant pericardial&#xD;
             effusion, cerebrovascular accident, transient ischemic attack.&#xD;
&#xD;
          -  Active infection requiring systemic therapy except for hepatitis C virus (HCV) and&#xD;
             hepatitis B virus (HBV).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Aichi Cancer Center Hospital</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iizuka Hospital</name>
      <address>
        <city>Iizuka</city>
        <state>Fukuoka</state>
        <zip>820-8505</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital, Department of Gastroenterology and Hepatology</name>
      <address>
        <city>Osaka-Sayama</city>
        <state>Osaka</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo</state>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyorin University Hospital, Department of Medical Oncology</name>
      <address>
        <city>Mitaka-shi</city>
        <state>Tokyo</state>
        <zip>181-8611</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Japanese Red Cross Musashino Hospital</name>
      <address>
        <city>Musashino</city>
        <state>Tokyo</state>
        <zip>180-8610</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization Kyushu Medical Center</name>
      <address>
        <city>Fukuoka</city>
        <zip>810-8563</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>https://pmiform.com/clinical-trial-info-request?StudyID=B9991024</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 19, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 21, 2017</study_first_posted>
  <results_first_submitted>August 13, 2020</results_first_submitted>
  <results_first_submitted_qc>September 1, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">September 4, 2020</results_first_posted>
  <last_update_submitted>September 1, 2020</last_update_submitted>
  <last_update_submitted_qc>September 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 4, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Hepatocellular carcinoma</keyword>
  <keyword>Liver disease</keyword>
  <keyword>Avelumab</keyword>
  <keyword>Axitinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Avelumab</mesh_term>
    <mesh_term>Axitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT03289533/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/33/NCT03289533/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants with advanced hepatocellular carcinoma (HCC) who did not receive any prior systemic therapy were enrolled in this study.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Avelumab + Axitinib</title>
          <description>Participants with advanced HCC were administered with Avelumab 10 milligram per kilogram (mg/kg) as 1-hour intravenous (IV) infusion, on Day 1 of each cycle along with Axitinib 5 milligram (mg) oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Terminated from study by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full analysis set included participants who received at least one dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Avelumab + Axitinib</title>
          <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.4" spread="14.98"/>
                  </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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03</title>
        <description>An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.</description>
        <time_frame>From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)</time_frame>
        <population>Safety analysis set included participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03</title>
          <description>An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.</description>
          <population>Safety analysis set included participants who received at least one dose of study drug.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Grade 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Abnormal Laboratory Parameter Values (Hematology) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 4.03</title>
        <description>As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (&lt;) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= &lt;100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (&gt;) 0 to 2 gram per deciliter(g/dL) above upper limit of normal [ULN]; lymphocyte count decreased: Grade 1= &lt;LLN to 0.8*10^9/L, Grade 2= &lt;0.8*10^9/L to 0.5*10^9/L, Grade 3= &lt;0.5*10^9/L to 0.2*10^9/L ; lymphocyte count increased: Grade 2= &gt;4*10^9/L to 20*10^9/L; neutrophil count decreased: Grade 1= &lt;LLN to 1.5*10^9/L ,Grade 2= &lt;1.5*10^9/L to 1.0*10^9/L; platelet count decreased: Grade 1= &lt;LLN to 75.0*10^9/L, Grade 2= &lt;75.0*10^9/L to 50.0*10^9/L; white blood cell decreased: Grade 1= &lt;LLN to 3*10^9/L, Grade 2= &lt;3*10^9/L to 2*10^9/L.</description>
        <time_frame>From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)</time_frame>
        <population>Safety analysis set included participants who received at least one dose of study drug. Categories with at least 1 participant with abnormality were reported in this outcome measure. One participant might have more than 1 abnormality.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Laboratory Parameter Values (Hematology) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 4.03</title>
          <description>As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (&lt;) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= &lt;100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (&gt;) 0 to 2 gram per deciliter(g/dL) above upper limit of normal [ULN]; lymphocyte count decreased: Grade 1= &lt;LLN to 0.8*10^9/L, Grade 2= &lt;0.8*10^9/L to 0.5*10^9/L, Grade 3= &lt;0.5*10^9/L to 0.2*10^9/L ; lymphocyte count increased: Grade 2= &gt;4*10^9/L to 20*10^9/L; neutrophil count decreased: Grade 1= &lt;LLN to 1.5*10^9/L ,Grade 2= &lt;1.5*10^9/L to 1.0*10^9/L; platelet count decreased: Grade 1= &lt;LLN to 75.0*10^9/L, Grade 2= &lt;75.0*10^9/L to 50.0*10^9/L; white blood cell decreased: Grade 1= &lt;LLN to 3*10^9/L, Grade 2= &lt;3*10^9/L to 2*10^9/L.</description>
          <population>Safety analysis set included participants who received at least one dose of study drug. Categories with at least 1 participant with abnormality were reported in this outcome measure. One participant might have more than 1 abnormality.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Anemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count decreased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocyte count increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophil count decreased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelet count decreased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cell decreased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White blood cell decreased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Abnormal Laboratory Parameter Values (Chemistry) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version (v) 4.03</title>
        <description>ALT,ALP,AST increased grades(g):g1&gt;ULN-3.0*ULN,g2&gt;3.0-5.0*ULN,g3&gt;5.0-20.0*ULN; blood bilirubin increased:g1&gt;ULN-1.5*ULN, g2&gt;1.5-3.0*ULN, g3&gt;3.0-10.0*ULN; [cholesterol high:g1&gt;ULN-7.75, g2 &gt;7.75-10.34,g4 &gt;12.92]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1&gt;ULN-2.5*ULN, g2&gt;2.5*ULN-5*ULN; Ggt increased g3 &gt;5.0-20.0*ULN; Creatinine increased: g1&gt;ULN-1.5*ULN; [hypoalbuminemia:g1&lt;LLN-30,g2&lt;30-20] grams per liter(g/L);[hyperglycemia:g1&gt; ULN-8.9,g2&gt; 8.9-13.9,g3&gt; 13.9-27.8;hypermagnesemia:g1&gt;ULN-1.23;hypercalcemia:g1&gt;ULN -2.9;hyperkalemia:g1&gt;ULN-5.5,hypernatremia:g1&gt;ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 &gt;3.42-5.7;hypocalcemia:g1&lt;LLN-2.0,hypoglycemia:g1&lt;LLN-3.0, g2&lt;3.0-2.2;hypokalemia:g2&lt;LLN-3.0,g4&lt;2.5,hypomagnesemia:g1&lt;LLN-0.5,hyponatremia:g1&lt;LLN-130, g3&lt;130-120,hypophosphatemia:g1&lt;LLN-0.8,g2&lt;0.8-0.6]mmol/L;lipase increased:g1&gt;ULN-1.5*ULN,g3 &gt;2.0-5.0*ULN;serum amylase increased:g1&gt;ULN-1.5*ULN, g2&gt;1.5-2.0*ULN,g3&gt;2.0-5.0*ULN.</description>
        <time_frame>From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)</time_frame>
        <population>Safety analysis set included participants who received at least one dose of study drug. Categories with at least 1 participant with abnormality were reported in this outcome measure. One participant might have more than 1 abnormality.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Laboratory Parameter Values (Chemistry) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version (v) 4.03</title>
          <description>ALT,ALP,AST increased grades(g):g1&gt;ULN-3.0*ULN,g2&gt;3.0-5.0*ULN,g3&gt;5.0-20.0*ULN; blood bilirubin increased:g1&gt;ULN-1.5*ULN, g2&gt;1.5-3.0*ULN, g3&gt;3.0-10.0*ULN; [cholesterol high:g1&gt;ULN-7.75, g2 &gt;7.75-10.34,g4 &gt;12.92]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1&gt;ULN-2.5*ULN, g2&gt;2.5*ULN-5*ULN; Ggt increased g3 &gt;5.0-20.0*ULN; Creatinine increased: g1&gt;ULN-1.5*ULN; [hypoalbuminemia:g1&lt;LLN-30,g2&lt;30-20] grams per liter(g/L);[hyperglycemia:g1&gt; ULN-8.9,g2&gt; 8.9-13.9,g3&gt; 13.9-27.8;hypermagnesemia:g1&gt;ULN-1.23;hypercalcemia:g1&gt;ULN -2.9;hyperkalemia:g1&gt;ULN-5.5,hypernatremia:g1&gt;ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 &gt;3.42-5.7;hypocalcemia:g1&lt;LLN-2.0,hypoglycemia:g1&lt;LLN-3.0, g2&lt;3.0-2.2;hypokalemia:g2&lt;LLN-3.0,g4&lt;2.5,hypomagnesemia:g1&lt;LLN-0.5,hyponatremia:g1&lt;LLN-130, g3&lt;130-120,hypophosphatemia:g1&lt;LLN-0.8,g2&lt;0.8-0.6]mmol/L;lipase increased:g1&gt;ULN-1.5*ULN,g3 &gt;2.0-5.0*ULN;serum amylase increased:g1&gt;ULN-1.5*ULN, g2&gt;1.5-2.0*ULN,g3&gt;2.0-5.0*ULN.</description>
          <population>Safety analysis set included participants who received at least one dose of study drug. Categories with at least 1 participant with abnormality were reported in this outcome measure. One participant might have more than 1 abnormality.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Alanine aminotransferase (ALT) increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT increased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline phosphatase (ALP) increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALP increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALP increased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate aminotransferase(AST) increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST increased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood bilirubin increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood bilirubin increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood bilirubin increased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cholesterol high: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cholesterol high: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cholesterol high: Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatine phosphokinase increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatine phosphokinase increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gamma-glutamyl transferase(Ggt) increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ggt increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ggt increased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypercalcemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperglycemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperglycemia: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperglycemia: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyperkalemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypermagnesemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypernatremia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertriglyceridemia; Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypertriglyceridemia; Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoalbuminemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoalbuminemia: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypocalcemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoglycemia: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypokalemia: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypokalemia: Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypomagnesemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatremia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hyponatremia: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypophosphatemia: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypophosphatemia: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lipase increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lipase increased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serum amylase increased: Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serum amylase increased: Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serum amylase increased: Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Disease Progression (TTP)</title>
        <description>TTP as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was define as time (in months) from date of first dose of study drug to date of first documentation of progressive disease (PD) or data censoring date, whichever occurred first. PD was defined as greater than or equal to (&gt;=) 20 percent (%) increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment), with a minimum absolute increase of at least 5 millimeter (mm), or appearance of &gt;=1 new lesions. TTP was analyzed by Kaplan-Meier method. TTP data was censored on the date the last adequate tumor assessment for participants without PD, for participants who start new anti-cancer treatment prior to PD, for participants who died without PD, or for participants with PD after &gt;=2 missing tumor assessments.</description>
        <time_frame>From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months)</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Disease Progression (TTP)</title>
          <description>TTP as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was define as time (in months) from date of first dose of study drug to date of first documentation of progressive disease (PD) or data censoring date, whichever occurred first. PD was defined as greater than or equal to (&gt;=) 20 percent (%) increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment), with a minimum absolute increase of at least 5 millimeter (mm), or appearance of &gt;=1 new lesions. TTP was analyzed by Kaplan-Meier method. TTP data was censored on the date the last adequate tumor assessment for participants without PD, for participants who start new anti-cancer treatment prior to PD, for participants who died without PD, or for participants with PD after &gt;=2 missing tumor assessments.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.52" lower_limit="1.91" upper_limit="7.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS)</title>
        <description>PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: &gt;= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of &gt;=5 mm, or appearance of &gt;=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after &gt;=2 missing tumor assessments.</description>
        <time_frame>From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS)</title>
          <description>PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: &gt;= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of &gt;=5 mm, or appearance of &gt;=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after &gt;=2 missing tumor assessments.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.52" lower_limit="1.91" upper_limit="7.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Objective Response (OR)</title>
        <description>OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;) 10 mm. PR was defined as &gt;=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
        <time_frame>From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months)</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Objective Response (OR)</title>
          <description>OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (&lt;) 10 mm. PR was defined as &gt;=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.6" lower_limit="2.9" upper_limit="34.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Disease Control (DC)</title>
        <description>Disease control as assessed by investigator according to RECIST v1.1, was defined as participants with CR, PR, stable disease (SD), or non-CR/non-PD. CR: disappearance of all target and non-target lesions and sustained for 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters. SD: 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: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm or appearance of &gt;=1 new lesions. Non-CR/non-PD: Persistence of any non-target lesions and/or tumor marker level above the normal limit at &gt;=8 weeks after date of first dose of study treatment.</description>
        <time_frame>From first dose of study drug until first documentation of CR or PR or SD or till non-CR/non-PD (maximum up to 20 months)</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Disease Control (DC)</title>
          <description>Disease control as assessed by investigator according to RECIST v1.1, was defined as participants with CR, PR, stable disease (SD), or non-CR/non-PD. CR: disappearance of all target and non-target lesions and sustained for 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters. SD: 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: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm or appearance of &gt;=1 new lesions. Non-CR/non-PD: Persistence of any non-target lesions and/or tumor marker level above the normal limit at &gt;=8 weeks after date of first dose of study treatment.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="68.2" lower_limit="45.1" upper_limit="86.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Tumor Response (TTR)</title>
        <description>TTR as assessed by investigator according to RECIST v1.1 was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters.</description>
        <time_frame>From first dose of study drug until first documentation of CR or PR (maximum up to 20 months)</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Tumor Response (TTR)</title>
          <description>TTR as assessed by investigator according to RECIST v1.1 was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.91" lower_limit="1.9" upper_limit="3.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DR)</title>
        <description>DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of &gt;=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after &gt;=2 missing tumor assessments.</description>
        <time_frame>From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug. Here, &quot;Overall Number of Participants Analyzed&quot; signifies participants evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DR)</title>
          <description>DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to &lt;10 mm. PR: &gt;= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of &gt;=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after &gt;=2 missing tumor assessments.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug. Here, &quot;Overall Number of Participants Analyzed&quot; signifies participants evaluable for this outcome measure.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.29" lower_limit="3.71" upper_limit="12.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.</description>
        <time_frame>From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 21 months)</time_frame>
        <population>Full analysis set included all participants who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.</description>
          <population>Full analysis set included all participants who received at least one dose of study drug.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.05" lower_limit="7.95" upper_limit="NA">Upper limit of 95% confidence interval (CI) could not be estimated due to low number of participants with event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Serum Concentration of Avelumab</title>
        <time_frame>Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days)</time_frame>
        <population>Pharmacokinetic (PK) analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for avelumab. Here, &quot;number analyzed&quot; signifies participants evaluable for specific time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Serum Concentration of Avelumab</title>
          <population>Pharmacokinetic (PK) analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for avelumab. Here, &quot;number analyzed&quot; signifies participants evaluable for specific time points.</population>
          <units>Microgram per milliliter</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="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="231.06" spread="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="228.48" spread="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="245.66" spread="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Plasma Concentration of Axitinib</title>
        <time_frame>Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days)</time_frame>
        <population>PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for axitinib. Here, &quot;number analyzed&quot; signifies participants evaluable for specific time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration of Axitinib</title>
          <population>PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for axitinib. Here, &quot;number analyzed&quot; signifies participants evaluable for specific time points.</population>
          <units>Nanograms per milliliter</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.70" spread="23.015"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="109.00" spread="17.275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pre-dose Serum Concentration of Avelumab</title>
        <time_frame>Pre-dose on Day 1 of Cycle 2, 3, 4, 6, 8, 12, 16, 20, 24, 28 (Duration of each cycle=14 days)</time_frame>
        <population>PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for avelumab. Here, &quot;number analyzed&quot; signifies participants evaluable at specific time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Pre-dose Serum Concentration of Avelumab</title>
          <population>PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for avelumab. Here, &quot;number analyzed&quot; signifies participants evaluable at specific time points.</population>
          <units>Microgram per milliliter</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="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="22"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.80" spread="17.722"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.419" spread="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 4 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.220" spread="118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 6 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.922" spread="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 8 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.814" spread="39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 12 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.832" spread="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 16 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.388" spread="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 20 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.211" spread="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 24 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.070" spread="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 28 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.578" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pre-dose Plasma Concentration of Axitinib</title>
        <time_frame>Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days)</time_frame>
        <population>PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for axitinib. Here, &quot;number analyzed&quot; signifies participants evaluable for specific time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Pre-dose Plasma Concentration of Axitinib</title>
          <population>PK analysis set included all participants who had received at least one dose of study drug and who had at least one of the PK parameters of interest for axitinib. Here, &quot;number analyzed&quot; signifies participants evaluable for specific time points.</population>
          <units>Nanograms per milliliter</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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6439" spread="123"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 3 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.2226" spread="164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status</title>
        <description>PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering &gt;= 1% of the tumor area. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering &lt; 1% of the tumor area.</description>
        <time_frame>Baseline (Day 1)</time_frame>
        <population>PD-L1 biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for PD-L1.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status</title>
          <description>PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering &gt;= 1% of the tumor area. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering &lt; 1% of the tumor area.</description>
          <population>PD-L1 biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for PD-L1.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PD-L1: Positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PD-L1: Negative</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells</title>
        <description>CD8+ cells are the type of T-lymphocytes. Invasive margin is defined as the region on each side of the border between tumor cells. Expression of CD8+ cells in invasive margin, center of tumor cells, total area of tumor cells has been reported as mean percentage of CD8+cells per unit area. Area was measured in millimeter square (mm^2).</description>
        <time_frame>From first dose of study drug up to end of treatment (maximum up to 20 months)</time_frame>
        <population>CD8+ biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for CD8+ cells. Here, &quot;number analyzed&quot; signifies participants evaluable for specific rows.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells</title>
          <description>CD8+ cells are the type of T-lymphocytes. Invasive margin is defined as the region on each side of the border between tumor cells. Expression of CD8+ cells in invasive margin, center of tumor cells, total area of tumor cells has been reported as mean percentage of CD8+cells per unit area. Area was measured in millimeter square (mm^2).</description>
          <population>CD8+ biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for CD8+ cells. Here, &quot;number analyzed&quot; signifies participants evaluable for specific rows.</population>
          <units>Percentage of CD8+cells per mm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>CD8+ Cells in Invasive Margin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.12" spread="1.760"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CD8+ Cells in Center of Tumor Cells</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.91" spread="1.328"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>CD8+ Cells in Total Area of Tumor Cells</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.02" spread="1.353"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells</title>
        <description>CD8+ cells are the type of T-lymphocytes.</description>
        <time_frame>From first dose of study drug up to end of treatment (up to 20 months)</time_frame>
        <population>CD8+ biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for CD8+ cells. Here, &quot;Overall Number of Participants Analyzed&quot; signifies the number of participants evaluable for this measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells</title>
          <description>CD8+ cells are the type of T-lymphocytes.</description>
          <population>CD8+ biomarker analysis set included participants who had received at least one dose of study drug and who had at least one screening biomarker assessment for CD8+ cells. Here, &quot;Overall Number of Participants Analyzed&quot; signifies the number of participants evaluable for this measure.</population>
          <units>mm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.88" spread="48.832"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)</title>
        <description>ADA positive was defined as presence of at least one positive ADA sample. nAb positive was defined as presence of at least one positive nAb sample.</description>
        <time_frame>From first dose of study drug until 30 days after the last dose of study drug (maximum up to 21 months)</time_frame>
        <population>The immunogenicity analysis set included participants who have received at least one dose of study drug and who had at least one ADA or nAb sample collected for avelumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Avelumab + Axitinib</title>
            <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)</title>
          <description>ADA positive was defined as presence of at least one positive ADA sample. nAb positive was defined as presence of at least one positive nAb sample.</description>
          <population>The immunogenicity analysis set included participants who have received at least one dose of study drug and who had at least one ADA or nAb sample collected for avelumab.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ADA positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>nAb positive</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)</time_frame>
      <desc>Same event may appear as both an adverse event (AE) and serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.</desc>
      <group_list>
        <group group_id="E1">
          <title>Avelumab + Axitinib</title>
          <description>Participants with advanced HCC were administered with Avelumab 10 mg/kg as 1-hour IV infusion, on Day 1 of each cycle along with Axitinib 5 mg oral tablets, twice daily on a continuous dosing schedule (without a break in dosing except in case of drug-related toxicity) until disease progression, participant refusal, unacceptable toxicity, lost to follow-up, or until study termination by the sponsor, whichever occurred first (up to maximum of 40 cycles). Duration of each cycle =14 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v22.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
              </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="22"/>
              </event>
              <event>
                <sub_title>Diverticulum intestinal haemorrhagic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v22.1</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="22" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Anal erosion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Glossitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Oedema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="22"/>
              </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="12" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </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="3" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
              </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="11" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="22"/>
              </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>Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pfizer ClinicalTrials.gov Call Center</name_or_title>
      <organization>Pfizer Inc.</organization>
      <phone>1-800-718-1021</phone>
      <email>ClinicalTrials.gov_Inquiries@pfizer.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/NCT03289533
org study id: B9991024
nct id: NCT03289533
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
To evaluate the safety, efficacy and PK of avelumab in combination with axitinib as first
      line treatment in patients with advanced HCC
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.03
time frame: From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
description: An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. AEs were graded by investigator according to NCI CTCAE v.4.03 as follows: Grade 1: mild AE, Grade 2: moderate AE, Grade 3: severe AE, Grade 4: life-threatening consequences and urgent intervention indicated, Grade 5: death related to AE.
measure: Number of Participants With Abnormal Laboratory Parameter Values (Hematology) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version 4.03
time frame: From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
description: As per NCI-CTCAE v 4.03, anemia Grade 1= Less than (<) lower limit of normal (LLN) to 100 gram per liter (g/L),Grade 2= <100 to 80 g/L; hemoglobin increased: Grade 1= increase of greater than (>) 0 to 2 gram per deciliter(g/dL) above upper limit of normal [ULN]; lymphocyte count decreased: Grade 1= <LLN to 0.8*10^9/L, Grade 2= <0.8*10^9/L to 0.5*10^9/L, Grade 3= <0.5*10^9/L to 0.2*10^9/L ; lymphocyte count increased: Grade 2= >4*10^9/L to 20*10^9/L; neutrophil count decreased: Grade 1= <LLN to 1.5*10^9/L ,Grade 2= <1.5*10^9/L to 1.0*10^9/L; platelet count decreased: Grade 1= <LLN to 75.0*10^9/L, Grade 2= <75.0*10^9/L to 50.0*10^9/L; white blood cell decreased: Grade 1= <LLN to 3*10^9/L, Grade 2= <3*10^9/L to 2*10^9/L.
measure: Number of Participants With Abnormal Laboratory Parameter Values (Chemistry) as Graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event (CTCAE) Version (v) 4.03
time frame: From first dose of study drug up to 30 days after last dose of study drug or initiation of new anti-cancer drug therapy, whichever occurred first (maximum up to 21 months)
description: ALT,ALP,AST increased grades(g):g1>ULN-3.0*ULN,g2>3.0-5.0*ULN,g3>5.0-20.0*ULN; blood bilirubin increased:g1>ULN-1.5*ULN, g2>1.5-3.0*ULN, g3>3.0-10.0*ULN; [cholesterol high:g1>ULN-7.75, g2 >7.75-10.34,g4 >12.92]millimoles per liter(mmol/L);creatine phosphokinase, gamma-glutamyl transferase(ggt) increased g1>ULN-2.5*ULN, g2>2.5*ULN-5*ULN; Ggt increased g3 >5.0-20.0*ULN; Creatinine increased: g1>ULN-1.5*ULN; [hypoalbuminemia:g1<LLN-30,g2<30-20] grams per liter(g/L);[hyperglycemia:g1> ULN-8.9,g2> 8.9-13.9,g3> 13.9-27.8;hypermagnesemia:g1>ULN-1.23;hypercalcemia:g1>ULN -2.9;hyperkalemia:g1>ULN-5.5,hypernatremia:g1>ULN-150;hypertriglyceridemia g1:1.71-3.42,g2 >3.42-5.7;hypocalcemia:g1<LLN-2.0,hypoglycemia:g1<LLN-3.0, g2<3.0-2.2;hypokalemia:g2<LLN-3.0,g4<2.5,hypomagnesemia:g1<LLN-0.5,hyponatremia:g1<LLN-130, g3<130-120,hypophosphatemia:g1<LLN-0.8,g2<0.8-0.6]mmol/L;lipase increased:g1>ULN-1.5*ULN,g3 >2.0-5.0*ULN;serum amylase increased:g1>ULN-1.5*ULN, g2>1.5-2.0*ULN,g3>2.0-5.0*ULN.
measure: Time to Disease Progression (TTP)
time frame: From first dose of study drug until first documentation of progressive disease or data censoring date, whichever occurred first (maximum up to 20 months)
description: TTP as assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, was define as time (in months) from date of first dose of study drug to date of first documentation of progressive disease (PD) or data censoring date, whichever occurred first. PD was defined as greater than or equal to (>=) 20 percent (%) increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment), with a minimum absolute increase of at least 5 millimeter (mm), or appearance of >=1 new lesions. TTP was analyzed by Kaplan-Meier method. TTP data was censored on the date the last adequate tumor assessment for participants without PD, for participants who start new anti-cancer treatment prior to PD, for participants who died without PD, or for participants with PD after >=2 missing tumor assessments.
measure: Progression Free Survival (PFS)
time frame: From first dose of study drug until first documentation of PD or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)
description: PFS as assessed by investigator per RECIST v1.1, was defined as time (in months) from date of first dose of study drug to date of first documentation of PD or death due to any cause or data censoring date, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions, taking as a reference smallest sum on study treatment (this included baseline sum if that was smallest on study treatment). The sum must also demonstrate absolute increase of >=5 mm, or appearance of >=1 new lesions. PFS was analyzed by Kaplan-Meier method. PFS data was censored on the date the last adequate tumor assessment for participants without an event (PD or death), for participants who started new anti-cancer treatment prior to PFS event, for participants with a PFS event after >=2 missing tumor assessments.
measure: Percentage of Participants With Objective Response (OR)
time frame: From first dose of study drug until disease progression or death due to any cause (maximum up to 20 months)
description: OR as assessed by investigator per RECIST v.1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR), were recorded from first dose of study drug until disease progression or death due to any cause. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as >=30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters.
measure: Percentage of Participants With Disease Control (DC)
time frame: From first dose of study drug until first documentation of CR or PR or SD or till non-CR/non-PD (maximum up to 20 months)
description: Disease control as assessed by investigator according to RECIST v1.1, was defined as participants with CR, PR, stable disease (SD), or non-CR/non-PD. CR: disappearance of all target and non-target lesions and sustained for 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameters of target lesions taking as reference baseline sum diameters. SD: 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: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm or appearance of >=1 new lesions. Non-CR/non-PD: Persistence of any non-target lesions and/or tumor marker level above the normal limit at >=8 weeks after date of first dose of study treatment.
measure: Time to Tumor Response (TTR)
time frame: From first dose of study drug until first documentation of CR or PR (maximum up to 20 months)
description: TTR as assessed by investigator according to RECIST v1.1 was defined as the time (in months) from the date of first dose of study drug to the first documentation of objective response (CR or PR) that was subsequently confirmed. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters.
measure: Duration of Response (DR)
time frame: From first documentation of CR or PR until first documentation of tumor progression or death due to any cause or data censoring date, whichever occurred first (maximum up to 20 months)
description: DR as assessed by investigator according to RECIST v1.1, was defined as the time from date of first documentation of objective response (CR or PR) to date of PD or death due to any cause, or data censoring date, whichever occurred first. CR: disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) reduced in short axis to <10 mm. PR: >= 30% decrease in sum of diameter of target lesions taking as reference baseline sum diameters. PD: at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study treatment, with absolute increase of at least 5 mm or appearance of >=1 new lesions. DR data was censored on the date of last adequate tumor assessment for participants without an event (CR, PR, PD or death), for participants who start new anti-cancer treatment prior to DR assessment, for participants with DR assessment after >=2 missing tumor assessments.
measure: Overall Survival (OS)
time frame: From first dose of study drug to date of death from any cause or data censoring date, whichever occurred first (maximum up to 21 months)
description: OS was defined as the time (in months) from the date of first dose of study drug to the date of death due to any cause or data censoring date, whichever occurred first. Participants last known to be alive were censored at the date of last contact. OS was analyzed by Kaplan-Meier method.
measure: Maximum Observed Serum Concentration of Avelumab
time frame: Pre-dose, at the end of avelumab infusion on Day 1 of Cycle 2, 3, 4 (Duration of each cycle=14 days)
measure: Maximum Observed Plasma Concentration of Axitinib
time frame: Pre-dose, 2 hours post dose Axitinib administration on Day 1 of Cycle 2, 3 (Duration of each cycle=14 days)
measure: Pre-dose Serum Concentration of Avelumab
time frame: Pre-dose on Day 1 of Cycle 2, 3, 4, 6, 8, 12, 16, 20, 24, 28 (Duration of each cycle=14 days)
measure: Pre-dose Plasma Concentration of Axitinib
time frame: Pre-dose on Day 1 of Cycle 2 and 3 (Duration of each cycle=14 days)
measure: Number of Participants With Their Target Programmed Death-Ligand 1 (PD-L1) Status
time frame: Baseline (Day 1)
description: PD-L1 status was defined as positive when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering >= 1% of the tumor area. PD-L1 status was defined as negative when PD-L1 staining of any intensity was observed in tumor-associated immune cells covering < 1% of the tumor area.
measure: Mean Percentage of CD8+ Cells in Per Unit Area of Invasive Margin, Center of Tumor Cells and Total Area of Tumor Cells
time frame: From first dose of study drug up to end of treatment (maximum up to 20 months)
description: CD8+ cells are the type of T-lymphocytes. Invasive margin is defined as the region on each side of the border between tumor cells. Expression of CD8+ cells in invasive margin, center of tumor cells, total area of tumor cells has been reported as mean percentage of CD8+cells per unit area. Area was measured in millimeter square (mm^2).
measure: Summary of Cluster of Differentiation 8 (CD8+) Cells Expression: Total Area Covered by CD8+ Cells in Center of Tumor Cells
time frame: From first dose of study drug up to end of treatment (up to 20 months)
description: CD8+ cells are the type of T-lymphocytes.
measure: Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Positive Neutralizing Antibodies (nAbs)
time frame: From first dose of study drug until 30 days after the last dose of study drug (maximum up to 21 months)
description: ADA positive was defined as presence of at least one positive ADA sample. nAb positive was defined as presence of at least one positive nAb sample.
arm group label: Experimental 1
arm group type: Experimental
description: Avelumab (MSB0010718C) in combination with axitinib (AG-013736)
intervention type: Drug
intervention name: Avelumab (MSB0010718C)
description: Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.
arm group label: Experimental 1
intervention type: Drug
intervention name: Axitinib (AG-013736)
description: Patients will receive avelumab 10 mg/kg Q2W in combination with axitinib 5 mg BID.
arm group label: Experimental 1
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
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country: Japan
url: https://pmiform.com/clinical-trial-info-request?StudyID=B9991024
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Avelumab
mesh term: Axitinib
sharing ipd: No
ipd description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
provided document: 
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participant flow: 
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outcome list: 
reported events: 
certain agreements: 
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