<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/NCT03273153</url>
  </required_header>
  <id_info>
    <org_study_id>CO39722</org_study_id>
    <secondary_id>2016-004387-18</secondary_id>
    <nct_id>NCT03273153</nct_id>
  </id_info>
  <brief_title>A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma</brief_title>
  <official_title>A Phase III, Open-Label, Multicenter, Two Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Patients With Previously Untreated Advanced BRAF V600 Wild-Type Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase III, multicenter, open-label, randomized study designed to evaluate the&#xD;
      efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with&#xD;
      pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    This study was terminated due to benefit/risk analysis.&#xD;
  </why_stopped>
  <start_date type="Actual">December 11, 2017</start_date>
  <completion_date type="Actual">February 19, 2021</completion_date>
  <primary_completion_date type="Actual">April 15, 2019</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)</measure>
    <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
    <description>PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of &gt;/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS as Determined by the Investigator</measure>
    <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
    <description>PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of &gt;/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response as Determined by the Investigator</measure>
    <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
    <description>Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions &gt;/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (&lt;10 mm short axis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response as Determined by IRC</measure>
    <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
    <description>Objective response, defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by IRC according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Week 16</time_frame>
    <description>DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (&lt;10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>From randomization up to approximately 3 years</time_frame>
    <description>OS is defined as the time from randomization to death from any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Objective Response Determined by the IRC</measure>
    <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
    <description>Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Objective Response Determined by the Investigator</measure>
    <time_frame>Up to 3 years</time_frame>
    <description>Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Two-year Landmark Survival</measure>
    <time_frame>At 2 years</time_frame>
    <description>Two-year landmark survival is defined as the rate of survival at 2 years. Two-year landmark survival is defined as the rate of survival at 2 years and was calculated using Kaplan-Meier analysis, which is commonly used to estimate the probability of an event at time 't.'</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Health-related Quality of Life (HRQoL) Scores</measure>
    <time_frame>Up to approximately 16 months. Follow up is reported at weeks after participant treatment discontinuation, which could occur at any time during the study. Total time frame does not exceed 16 months.</time_frame>
    <description>HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher (&quot;better&quot;) level of functioning.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs)</measure>
    <time_frame>Up to approximately 16 months</time_frame>
    <description>An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Vital Signs</measure>
    <time_frame>From baseline up to approximately 3 years</time_frame>
    <description>Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Laboratory Abnormalities</measure>
    <time_frame>Up to approximately 16 months</time_frame>
    <description>Participants with laboratory abnormalities (values outside of a defined range) will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Cobimetinib</measure>
    <time_frame>Days 1 and 15 of Cycle 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of Atezolizumab</measure>
    <time_frame>Day 1 of Cycles 1, 2, and 3</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Anti-drug Antibodies (ADAs)</measure>
    <time_frame>Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation</time_frame>
    <description>Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">446</enrollment>
  <condition>Advanced BRAFV600 Wild-type Melanoma</condition>
  <arm_group>
    <arm_group_label>Cobimetinib and Atezolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive 200 mg of pembrolizumab administered by IV infusion every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cobimetinib</intervention_name>
    <description>Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.</description>
    <arm_group_label>Cobimetinib and Atezolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Atezolizumab 840 mg as IV infusion once in every 2 weeks.</description>
    <arm_group_label>Cobimetinib and Atezolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab 200 mg as IV infusion once in every 3 weeks.</description>
    <arm_group_label>Pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Disease-Specific Inclusion Criteria&#xD;
&#xD;
          -  Histologically confirmed locally advanced and unresectable or metastatic melanoma&#xD;
&#xD;
          -  Naive to prior systemic anti-cancer therapy for melanoma&#xD;
&#xD;
          -  Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a&#xD;
             clinical mutation test approved by the local health authority&#xD;
&#xD;
          -  A representative, formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a&#xD;
             paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial&#xD;
             sections must be submitted along with an associated pathology report prior to study&#xD;
             entry. If 20 slides are not available or the tissue block is not of sufficient size,&#xD;
             the patient may still be eligible for the study, after discussion with and approval by&#xD;
             the Medical Monitor&#xD;
&#xD;
          -  Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             v1.1&#xD;
&#xD;
          -  Age &gt;=18 years at time of signing Informed Consent Form&#xD;
&#xD;
          -  Ability to comply with the study protocol, in the investigator's judgment&#xD;
&#xD;
          -  Histologically or cytologically confirmed BRAFV600 wild-type melanoma&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1&#xD;
&#xD;
          -  Life expectancy &gt;=3 months&#xD;
&#xD;
          -  Adequate hematologic and end-organ function&#xD;
&#xD;
          -  For women of childbearing potential: agreement to remain abstinent or use at least two&#xD;
             forms of effective contraceptive with a failure rate of &lt; 1% per year during the&#xD;
             treatment period and for at least 3 months after the last dose of cobimetinib and at&#xD;
             least 5 months after the last dose of atezolizumab or pembrolizumab&#xD;
&#xD;
          -  For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use&#xD;
             contraceptive measures (e.g. condom), and agreement to refrain from donating sperm,&#xD;
             for at least 3 months after the last dose of cobimetinib&#xD;
&#xD;
          -  Willingness and ability of patients to report selected study outcomes (e.g., GHS and&#xD;
             HRQoL) using an electronic device or paper backup questionnaires.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General Exclusion Criteria&#xD;
&#xD;
          -  Inability to swallow medications&#xD;
&#xD;
          -  Malabsorption condition that would alter the absorption of orally administered&#xD;
             medications&#xD;
&#xD;
          -  Pregnancy, breastfeeding, or intention of becoming pregnant during the study&#xD;
&#xD;
          -  History of severe hypersensitivity reactions to components of the cobimetinib,&#xD;
             atezolizumab, or pembrolizumab formulations&#xD;
&#xD;
          -  Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or&#xD;
             systemic immunostimulatory/immunosuppresive medication&#xD;
&#xD;
          -  Any serious medical condition or abnormality in clinical laboratory tests that, in the&#xD;
             investigator's judgment, precludes the patient's safe participation in and completion&#xD;
             of the study Cancer-Related Exclusion Criteria&#xD;
&#xD;
          -  Ocular melanoma&#xD;
&#xD;
          -  Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation&#xD;
             of needing such procedure while receiving study treatment&#xD;
&#xD;
          -  Uncontrolled tumor-related pain&#xD;
&#xD;
          -  Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated&#xD;
             drainage more than once every 28 days&#xD;
&#xD;
          -  Active or untreated central nervous system (CNS) metastases Exclusions Related to&#xD;
             Cardiovascular Disease&#xD;
&#xD;
          -  Unstable angina, new-onset angina within last 3 months, myocardial infarction within&#xD;
             the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure&#xD;
             classified as New York Heart Association Class II or higher&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or&#xD;
             &lt;50%, whichever is lower&#xD;
&#xD;
          -  Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic&#xD;
             baseline hypertension consistently above 159/99 mmHg despite optimal medical&#xD;
             management&#xD;
&#xD;
          -  History or presence of an abnormal electrocardiogram (ECG) that is clinically&#xD;
             significant in the investigator's opinion, including complete left bundle branch&#xD;
             block, second- or third degree heart block, or evidence of prior myocardial infarction&#xD;
             Exclusions Related to Infections&#xD;
&#xD;
          -  HIV infection&#xD;
&#xD;
          -  Active tuberculosis infection&#xD;
&#xD;
          -  Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited&#xD;
             to, hospitalization for complications of infection, bacteremia, or severe pneumonia&#xD;
&#xD;
          -  Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of&#xD;
             Cycle 1&#xD;
&#xD;
          -  Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1&#xD;
&#xD;
          -  Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular&#xD;
             Disease&#xD;
&#xD;
          -  Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and&#xD;
             Immunomodulatory Drugs&#xD;
&#xD;
          -  Active or history of autoimmune disease or immune deficiency&#xD;
&#xD;
          -  Prior allogeneic stem cell or solid organ transplantation&#xD;
&#xD;
          -  History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or&#xD;
             idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan&#xD;
&#xD;
          -  Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1,&#xD;
             Cycle 1 Exclusions Related to Other Medical Conditions or Medications&#xD;
&#xD;
          -  Active malignancy (other than melanoma) or a prior malignancy within the past 3 years&#xD;
&#xD;
          -  Any Grade &gt;=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1&#xD;
&#xD;
          -  History of stroke, reversible ischemic neurological defect, or transient ischemic&#xD;
             attack within 6 months prior to Day 1&#xD;
&#xD;
          -  Proteinuria &gt;3.5 gm/24 hr&#xD;
&#xD;
          -  Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme&#xD;
             inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study&#xD;
             treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Chair</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Arizona Cancer Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85719</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC Norris Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC Norris Cancer Center; USC Oncology Hematology Newport Beach</name>
      <address>
        <city>Newport Beach</city>
        <state>California</state>
        <zip>92663</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California at Irvine Medical Center; Department of Oncology</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford Comprehensive Cancer Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UF Health Cancer Center at Orlando Health</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32824</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialist, North Region</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital;Hematology/ Oncology</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth-Hitchcock Medical Center; Hematology/Oncology</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Medical Center</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07962</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Forsythe Memorial Hospital Inc., dba Novant Health Oncology Specialists</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TriHealth Hatton Institute; Surgical Education</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Luke's University Health network</name>
      <address>
        <city>Bethlehem</city>
        <state>Pennsylvania</state>
        <zip>18015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomas Jefferson University Hospital;Medical Oncology</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SCRI Tennessee Oncology Chattanooga</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M.D Anderson Cancer Center; Uni of Texas At Houston</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Virginia University Hospitals Inc</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cairns Base Hospital</name>
      <address>
        <city>Cairns</city>
        <state>Queensland</state>
        <zip>4870</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Townsville General Hospital</name>
      <address>
        <city>Douglas</city>
        <state>Queensland</state>
        <zip>4184</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital</name>
      <address>
        <city>Woolloongabba</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Hobart Hospital</name>
      <address>
        <city>Hobart</city>
        <state>Tasmania</state>
        <zip>7000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fiona Stanley Hospital</name>
      <address>
        <city>Murdoch</city>
        <state>Western Australia</state>
        <zip>6150</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires St-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Groeninge</name>
      <address>
        <city>Kortrijk</city>
        <zip>8500</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cancer - INCa; Oncologia</name>
      <address>
        <city>Rio de Janeiro</city>
        <state>RJ</state>
        <zip>20560-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital das Clinicas - UFRGS</name>
      <address>
        <city>Porto Alegre</city>
        <state>RS</state>
        <zip>90035-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Avicenne; Dermatologie</name>
      <address>
        <city>Bobigny</city>
        <zip>93009</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Andre CHU De Bordeaux; Dermatologie</name>
      <address>
        <city>Bordeaux</city>
        <zip>33075</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Site Du Bocage;Dermatologie</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Grenoble - Hôpital Nord</name>
      <address>
        <city>Grenoble</city>
        <zip>38043</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Le Mans; Dermatologie</name>
      <address>
        <city>Le Mans</city>
        <zip>72037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Claude Huriez; Sce Dermatologie</name>
      <address>
        <city>Lille</city>
        <zip>59037</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Timone Adultes; Dermatologie</name>
      <address>
        <city>Marseille</city>
        <zip>13385</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Nantes; Cancéro-dermatologie</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital l Archet 2; Ginestriere, Service de; Dermatologie</name>
      <address>
        <city>Nice cedex 3</city>
        <zip>06200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Groupe Hospitalier Bichat Claude Bernard</name>
      <address>
        <city>Paris</city>
        <zip>75018</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint Louis; Dermatologie 1</name>
      <address>
        <city>Paris</city>
        <zip>75475</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Robert Debre; DERMATOLOGIE</name>
      <address>
        <city>Reims</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Eugene Marquis; Service d'oncologie</name>
      <address>
        <city>Rennes</city>
        <zip>35042</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Charles Nicolle; Dermatologie Serv.</name>
      <address>
        <city>Rouen</city>
        <zip>76031</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)</name>
      <address>
        <city>Toulouse</city>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy; Dermatologie</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum &quot;Carl Gustav Carus&quot;; Klinik und Poliklinik für Dermatologie</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HELIOS Klinikum Erfurt; Klinik für Dermatologie &amp; Allergologie</name>
      <address>
        <city>Erfurt</city>
        <zip>99089</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Essen; Klinik für Dermatologie</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie</name>
      <address>
        <city>Frankfurt</city>
        <zip>60590</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie</name>
      <address>
        <city>Gera</city>
        <zip>07548</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie</name>
      <address>
        <city>Hannover</city>
        <zip>30625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Mainz; Klinik und Poliklinik fur Dermatologie</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie</name>
      <address>
        <city>Mannheim</city>
        <zip>68167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johannes Wesling Klinikum Minden; Hämatologie, Onkologie, Hämostaseologie und Palliativmedizin</name>
      <address>
        <city>Minden</city>
        <zip>32429</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Ludwigs-Maximilians-Universität München; Dermatologie</name>
      <address>
        <city>München</city>
        <zip>80337</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fachklinik Hornheide; Dermatologie</name>
      <address>
        <city>Münster</city>
        <zip>48157</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen</name>
      <address>
        <city>Tübingen</city>
        <zip>72076</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine</name>
      <address>
        <city>Athens</city>
        <zip>115 22</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laiko General Hospital Athen</name>
      <address>
        <city>Athens</city>
        <zip>115 27</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metropolitan Hospital; Dept. of Oncology</name>
      <address>
        <city>Pireaus</city>
        <zip>185 47</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bioclinic Thessaloniki</name>
      <address>
        <city>Thessaloniki</city>
        <zip>546 22</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly</name>
      <address>
        <city>Budapest</city>
        <zip>1122</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika</name>
      <address>
        <city>Pecs</city>
        <zip>7632</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Szeged Szent-Györgyi Albert Clinical Center; Department of Dermatology and Allergology</name>
      <address>
        <city>Szeged</city>
        <zip>6720</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O. Universitaria Policlinico Di Modena; Ematologia</name>
      <address>
        <city>Modena</city>
        <state>Emilia-Romagna</state>
        <zip>41124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IFO - Istituto Regina Elena; Oncologia Medica</name>
      <address>
        <city>Roma</city>
        <state>Lazio</state>
        <zip>00144</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A</name>
      <address>
        <city>Genova</city>
        <state>Liguria</state>
        <zip>16132</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20133</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica</name>
      <address>
        <city>Milano</city>
        <state>Lombardia</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico</name>
      <address>
        <city>Candiolo</city>
        <state>Piemonte</state>
        <zip>10060</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.O.U. Cons. Policlinico Bari - Consorzlale Policlinico; Scienze Biomediche e Oncologia Umana</name>
      <address>
        <city>Bari</city>
        <state>Puglia</state>
        <zip>70124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico</name>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IOV - Istituto Oncologico Veneto IRCCS</name>
      <address>
        <city>Padova</city>
        <state>Veneto</state>
        <zip>35128</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphia Ziekenhuis, locatie Langendijk;Oncology</name>
      <address>
        <city>Breda</city>
        <zip>4818 CK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015AA</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zuyderland ziekenhuis locatie Geleen</name>
      <address>
        <city>Sittard-Geleen</city>
        <zip>6162 BG</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii</name>
      <address>
        <city>Gdansk</city>
        <zip>80-219</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej</name>
      <address>
        <city>Lublin</city>
        <zip>20-090</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.</name>
      <address>
        <city>Poznań</city>
        <zip>60-780</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych</name>
      <address>
        <city>Szczecin</city>
        <zip>71-730</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy</name>
      <address>
        <city>Warszawa</city>
        <zip>02-781</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii</name>
      <address>
        <city>Wrocław</city>
        <zip>53-413</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moscow City Oncology Hospital #62</name>
      <address>
        <city>Moscovskaya Oblast</city>
        <state>Moskovskaja Oblast</state>
        <zip>143423</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBSI &quot;Russian Oncological Scientific Center n.a. N.N. Blokhin&quot;</name>
      <address>
        <city>Moscow</city>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FBI &quot;Scientific Research Institute of Oncology n. a. N. N. Petrov&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Petersburg Oncology Hospital</name>
      <address>
        <city>St Petersburg</city>
        <zip>198255</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Son Espases; Servicio de Oncologia</name>
      <address>
        <city>Palma De Mallorca</city>
        <state>Islas Baleares</state>
        <zip>07014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia</name>
      <address>
        <city>Santiago de Compostela</city>
        <state>LA Coruña</state>
        <zip>15706</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia</name>
      <address>
        <city>Las Palmas de Gran Canaria</city>
        <state>LAS Palmas</state>
        <zip>35016</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universitaria de Navarra; Servicio de oncología</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Univ Vall d'Hebron; Servicio de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clínic i Provincial; Servicio de Oncología</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramon y Cajal; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz; Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena; Servicio de Oncologia</name>
      <address>
        <city>Sevilla</city>
        <zip>41009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Valenciano Oncologia; Oncologia Medica</name>
      <address>
        <city>Valencia</city>
        <zip>46009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Valencia; Servicio de oncologia</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Miguel Servet; Servicio Oncologia</name>
      <address>
        <city>Zaragoza</city>
        <zip>50009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R &amp; D department</name>
      <address>
        <city>Bristol</city>
        <zip>BS2 8HW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Western General Hospital; Edinburgh Cancer Center</name>
      <address>
        <city>Edinburgh</city>
        <zip>EH4 2XU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leicester Royal Infirmary; Dept. of Medical Oncology</name>
      <address>
        <city>Leicester</city>
        <zip>LE1 5WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University College London Hospital</name>
      <address>
        <city>London</city>
        <zip>NW1 - 2PG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guys &amp; St Thomas Hospital; Department of Oncology</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital</name>
      <address>
        <city>Stoke-On-Trent</city>
        <zip>ST4 6QG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Singleton Hospital; Pharmacy</name>
      <address>
        <city>Swansea</city>
        <zip>SA2 8QA</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Cornwall Hospital</name>
      <address>
        <city>Truro</city>
        <zip>TR1 3LQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>France</country>
    <country>Germany</country>
    <country>Greece</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
    <country>New Zealand</country>
  </removed_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <results_first_submitted>April 14, 2020</results_first_submitted>
  <results_first_submitted_qc>May 27, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 9, 2020</results_first_posted>
  <last_update_submitted>August 24, 2022</last_update_submitted>
  <last_update_submitted_qc>August 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Atezolizumab</mesh_term>
  </intervention_browse>
  <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>February 5, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03273153/Prot_002.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 3, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03273153/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab</title>
          <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
        </group>
        <group group_id="P2">
          <title>Cobimetinib and Atezolizumab</title>
          <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="224"/>
                <participants group_id="P2" count="222"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="224"/>
                <participants group_id="P2" count="222"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Missing</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Symptomatic Deterioration</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="112"/>
                <participants group_id="P2" count="102"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="25"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
                <participants group_id="P2" count="69"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Pembrolizumab</title>
          <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
        </group>
        <group group_id="B2">
          <title>Cobimetinib and Atezolizumab</title>
          <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="224"/>
            <count group_id="B2" value="222"/>
            <count group_id="B3" value="446"/>
          </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="63.5" spread="12.9"/>
                    <measurement group_id="B2" value="63.6" spread="13.1"/>
                    <measurement group_id="B3" value="63.6" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="83"/>
                    <measurement group_id="B2" value="93"/>
                    <measurement group_id="B3" value="176"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="141"/>
                    <measurement group_id="B2" value="129"/>
                    <measurement group_id="B3" value="270"/>
                  </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="7"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="190"/>
                    <measurement group_id="B2" value="180"/>
                    <measurement group_id="B3" value="370"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="198"/>
                    <measurement group_id="B2" value="188"/>
                    <measurement group_id="B3" value="386"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)</title>
        <description>PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of &gt;/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.</description>
        <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)</title>
          <description>PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of &gt;/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.</description>
          <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="224"/>
                <count group_id="O2" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" lower_limit="3.7" upper_limit="9.6"/>
                    <measurement group_id="O2" value="5.5" lower_limit="3.8" upper_limit="7.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2954</p_value>
            <method>Regression, Cox</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>1.15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.88</ci_lower_limit>
            <ci_upper_limit>1.50</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PFS as Determined by the Investigator</title>
        <description>PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of &gt;/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.</description>
        <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>PFS as Determined by the Investigator</title>
          <description>PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of &gt;/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.</description>
          <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="224"/>
                <count group_id="O2" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2" lower_limit="3.8" upper_limit="10.1"/>
                    <measurement group_id="O2" value="5.6" lower_limit="3.9" upper_limit="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response as Determined by the Investigator</title>
        <description>Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions &gt;/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (&lt;10 mm short axis).</description>
        <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response as Determined by the Investigator</title>
          <description>Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions &gt;/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (&lt;10 mm short axis).</description>
          <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="221"/>
                <count group_id="O2" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.7" lower_limit="30.29" upper_limit="43.38"/>
                    <measurement group_id="O2" value="27.9" lower_limit="22.13" upper_limit="34.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Objective Response as Determined by IRC</title>
        <description>Objective response, defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by IRC according to RECIST v1.1</description>
        <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response as Determined by IRC</title>
          <description>Objective response, defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by IRC according to RECIST v1.1</description>
          <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="206"/>
                <count group_id="O2" value="204"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.6" lower_limit="25.27" upper_limit="38.38"/>
                    <measurement group_id="O2" value="26.0" lower_limit="20.11" upper_limit="32.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR)</title>
        <description>DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (&lt;10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.</description>
        <time_frame>Week 16</time_frame>
        <population>The analysis for this outcome measure was limited to participants meeting the criteria provided in the description.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR)</title>
          <description>DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to &lt;10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (&lt;10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.</description>
          <population>The analysis for this outcome measure was limited to participants meeting the criteria provided in the description.</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="221"/>
                <count group_id="O2" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Investigator-assessed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="221"/>
                    <count group_id="O2" value="222"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.8" lower_limit="43.00" upper_limit="56.56"/>
                    <measurement group_id="O2" value="46.8" lower_limit="40.14" upper_limit="53.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IRC-assessed</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="206"/>
                    <count group_id="O2" value="204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.2" lower_limit="37.28" upper_limit="51.24"/>
                    <measurement group_id="O2" value="45.6" lower_limit="38.62" upper_limit="52.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>OS is defined as the time from randomization to death from any cause.</description>
        <time_frame>From randomization up to approximately 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS is defined as the time from randomization to death from any cause.</description>
          <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="224"/>
                <count group_id="O2" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.3" lower_limit="21.5" upper_limit="NA">Values are not estimable due to an insufficient number of participants with the event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="24.1" upper_limit="NA">Values are not estimable due to an insufficient number of participants with the event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Objective Response Determined by the IRC</title>
        <description>Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.</description>
        <time_frame>Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Objective Response Determined by the IRC</title>
          <description>Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.</description>
          <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="206"/>
                <count group_id="O2" value="204"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Values are not estimable due to an insufficient number of participants with the event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="9.2" upper_limit="NA">Values are not estimable due to an insufficient number of participants with the event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Objective Response Determined by the Investigator</title>
        <description>Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.</description>
        <time_frame>Up to 3 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Objective Response Determined by the Investigator</title>
          <description>Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.</description>
          <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="221"/>
                <count group_id="O2" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">Values are not estimable due to an insufficient number of participants with the event.</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="9.2" upper_limit="NA">Values are not estimable due to an insufficient number of participants with the event.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Two-year Landmark Survival</title>
        <description>Two-year landmark survival is defined as the rate of survival at 2 years. Two-year landmark survival is defined as the rate of survival at 2 years and was calculated using Kaplan-Meier analysis, which is commonly used to estimate the probability of an event at time 't.'</description>
        <time_frame>At 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Two-year Landmark Survival</title>
          <description>Two-year landmark survival is defined as the rate of survival at 2 years. Two-year landmark survival is defined as the rate of survival at 2 years and was calculated using Kaplan-Meier analysis, which is commonly used to estimate the probability of an event at time 't.'</description>
          <units>Percentage</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="224"/>
                <count group_id="O2" value="222"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.88" lower_limit="48.25" upper_limit="67.52"/>
                    <measurement group_id="O2" value="60.19" lower_limit="51.58" upper_limit="68.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Health-related Quality of Life (HRQoL) Scores</title>
        <description>HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher (&quot;better&quot;) level of functioning.</description>
        <time_frame>Up to approximately 16 months. Follow up is reported at weeks after participant treatment discontinuation, which could occur at any time during the study. Total time frame does not exceed 16 months.</time_frame>
        <population>The analysis population for this endpoint was the patient reported outcome (PRO) population evaluable participants for EORTC QLQ-C30.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Health-related Quality of Life (HRQoL) Scores</title>
          <description>HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher (&quot;better&quot;) level of functioning.</description>
          <population>The analysis population for this endpoint was the patient reported outcome (PRO) population evaluable participants for EORTC QLQ-C30.</population>
          <units>Units on a Scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="174"/>
                <count group_id="O2" value="160"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline value</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="173"/>
                    <count group_id="O2" value="160"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.27" spread="20.41"/>
                    <measurement group_id="O2" value="73.85" spread="19.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="131"/>
                    <count group_id="O2" value="124"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.99" spread="17.05"/>
                    <measurement group_id="O2" value="-9.14" spread="20.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="119"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.15" spread="18.67"/>
                    <measurement group_id="O2" value="-5.21" spread="18.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.77" spread="19.93"/>
                    <measurement group_id="O2" value="-7.65" spread="21.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="79"/>
                    <count group_id="O2" value="75"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.16" spread="15.02"/>
                    <measurement group_id="O2" value="-6.44" spread="20.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="74"/>
                    <count group_id="O2" value="66"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.69" spread="17.50"/>
                    <measurement group_id="O2" value="-6.31" spread="19.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="59"/>
                    <count group_id="O2" value="57"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.84" spread="19.82"/>
                    <measurement group_id="O2" value="-2.49" spread="15.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="44"/>
                    <count group_id="O2" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.46" spread="19.07"/>
                    <measurement group_id="O2" value="-3.86" spread="19.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 32</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                    <count group_id="O2" value="34"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.88" spread="22.41"/>
                    <measurement group_id="O2" value="-4.66" spread="20.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 36</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="24"/>
                    <count group_id="O2" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.17" spread="20.56"/>
                    <measurement group_id="O2" value="-6.00" spread="18.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 40</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.22" spread="19.38"/>
                    <measurement group_id="O2" value="-4.63" spread="21.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 44</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="10"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.46" spread="19.27"/>
                    <measurement group_id="O2" value="1.67" spread="12.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 48</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.64" spread="13.04"/>
                    <measurement group_id="O2" value="0.00" spread="15.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 52</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.67" spread="12.36"/>
                    <measurement group_id="O2" value="8.33" spread="15.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 56</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.11" spread="17.21"/>
                    <measurement group_id="O2" value="-2.08" spread="4.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 60</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.33" spread="11.79"/>
                    <measurement group_id="O2" value="-4.17" spread="5.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 64</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.33" spread="NA">Value is NA due to an insufficient number of participants with the event at this timepoint.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Discontinuation</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="78"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.05" spread="22.53"/>
                    <measurement group_id="O2" value="-14.42" spread="25.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="12"/>
                    <count group_id="O2" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.64" spread="14.85"/>
                    <measurement group_id="O2" value="-2.27" spread="18.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="31"/>
                    <count group_id="O2" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.25" spread="21.96"/>
                    <measurement group_id="O2" value="-14.10" spread="24.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="23"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.38" spread="24.34"/>
                    <measurement group_id="O2" value="-24.31" spread="28.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.73" spread="19.53"/>
                    <measurement group_id="O2" value="-23.61" spread="23.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up 20</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.83" spread="26.53"/>
                    <measurement group_id="O2" value="-8.33" spread="12.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.71" spread="29.36"/>
                    <measurement group_id="O2" value="-10.00" spread="14.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow-up 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-27.78" spread="22.15"/>
                    <measurement group_id="O2" value="-16.67" spread="23.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs)</title>
        <description>An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
        <time_frame>Up to approximately 16 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs)</title>
          <description>An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
          <units>Number of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="216"/>
                <count group_id="O2" value="220"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="195"/>
                    <measurement group_id="O2" value="218"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Vital Signs</title>
        <description>Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.</description>
        <time_frame>From baseline up to approximately 3 years</time_frame>
        <population>N for each assessment = participants without abnormalities at baseline or with missing baseline values</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Vital Signs</title>
          <description>Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.</description>
          <population>N for each assessment = participants without abnormalities at baseline or with missing baseline values</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="216"/>
                <count group_id="O2" value="220"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Sitting diastolic blood pressure - low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="210"/>
                    <count group_id="O2" value="214"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sitting diastolic blood pressure - high</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="150"/>
                    <count group_id="O2" value="138"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77"/>
                    <measurement group_id="O2" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sitting systolic blood pressure - low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sitting systolic blood pressure - high</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="69"/>
                    <count group_id="O2" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53"/>
                    <measurement group_id="O2" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pulse rate - low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="199"/>
                    <count group_id="O2" value="196"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pulse rate - high</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="208"/>
                    <count group_id="O2" value="214"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory rate - low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="209"/>
                    <count group_id="O2" value="219"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Respiratory rate - high</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="194"/>
                    <count group_id="O2" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55"/>
                    <measurement group_id="O2" value="52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temperature - low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="121"/>
                    <count group_id="O2" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="91"/>
                    <measurement group_id="O2" value="93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Temperature - high</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="213"/>
                    <count group_id="O2" value="214"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Laboratory Abnormalities</title>
        <description>Participants with laboratory abnormalities (values outside of a defined range) will be reported.</description>
        <time_frame>Up to approximately 16 months</time_frame>
        <population>Participants with at least one post-baseline assessment for a given laboratory value were included in this assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
          </group>
          <group group_id="O2">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Laboratory Abnormalities</title>
          <description>Participants with laboratory abnormalities (values outside of a defined range) will be reported.</description>
          <population>Participants with at least one post-baseline assessment for a given laboratory value were included in this assessment.</population>
          <units>Number of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="216"/>
                <count group_id="O2" value="220"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>SGPT/ALT</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Amylase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="201"/>
                    <count group_id="O2" value="204"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SGOT/AST</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="215"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatine Kinase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="215"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="210"/>
                    <count group_id="O2" value="218"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Triacylglycerol Lipase</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="197"/>
                    <count group_id="O2" value="200"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Magnesium</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="215"/>
                    <count group_id="O2" value="217"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Phosphorus</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="217"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Uric Acid</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="179"/>
                    <count group_id="O2" value="188"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes Abs</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="173"/>
                    <count group_id="O2" value="178"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils, Total, Abs</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="174"/>
                    <count group_id="O2" value="179"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Leukocyte Count</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="216"/>
                    <count group_id="O2" value="220"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Plasma Concentration of Cobimetinib</title>
        <time_frame>Days 1 and 15 of Cycle 1</time_frame>
        <population>PK data was not available from all participants at all time points due to study continuation or missed PK sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Plasma Concentration of Cobimetinib</title>
          <population>PK data was not available from all participants at all time points due to study continuation or missed PK sampling.</population>
          <units>nanograms/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="202"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.2" spread="614.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15 pre-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="142"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126" spread="284.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 1 Day 15 post-dose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="130"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="231" spread="213.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum Concentration of Atezolizumab</title>
        <time_frame>Day 1 of Cycles 1, 2, and 3</time_frame>
        <population>PK data was not available from all participants at all time points due to study continuation or missed PK sampling.</population>
        <group_list>
          <group group_id="O1">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Serum Concentration of Atezolizumab</title>
          <population>PK data was not available from all participants at all time points due to study continuation or missed PK sampling.</population>
          <units>micrograms/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="196"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Cycle 1 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="196"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="256" spread="35.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cycle 2 Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="163"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.2" spread="177.1"/>
                  </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="142"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="126" spread="104.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Anti-drug Antibodies (ADAs)</title>
        <description>Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.</description>
        <time_frame>Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation</time_frame>
        <population>Only participants from the Cobimetinib and Atezolizumab arm are included in this endpoint as it is meant to evaluate the immune response to atezolizumab.</population>
        <group_list>
          <group group_id="O1">
            <title>Cobimetinib and Atezolizumab</title>
            <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Anti-drug Antibodies (ADAs)</title>
          <description>Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.</description>
          <population>Only participants from the Cobimetinib and Atezolizumab arm are included in this endpoint as it is meant to evaluate the immune response to atezolizumab.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="210"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>For up to 135 days after the last dose of study drug, or until a new systemic anti-cancer therapy was initiated, whichever occurred first (a maximum of approximately 3 years).</time_frame>
      <desc>Adverse events (serious and other) were evaluated for the safety-evaluable population, which consisted of all participants who received at least one dose of study treatment. All-cause mortality is reported for the entire study population.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab</title>
          <description>Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.</description>
        </group>
        <group group_id="E2">
          <title>Cobimetinib and Atezolizumab</title>
          <description>Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v23.1</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="68" subjects_at_risk="224"/>
                <counts group_id="E2" subjects_affected="70" subjects_at_risk="222"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="56" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="105" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Cardiac failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Myocarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Tachyarrhythmia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Cardiac tamponade</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </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="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Chorioretinopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Visual impairment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Diplopia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Autoimmune colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Ascites</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Gastrointestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Subileus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Thrombosis mesenteric vessel</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hepatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Autoimmune hepatitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Cholestasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hepatic cirrhosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hepatic pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Erysipelas</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Diarrhoea infectious</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Encephalitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Urosepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dacryocystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Device related sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Endocarditis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pneumonia viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Spleen tuberculosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Superinfection viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Tonsilitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Toxic shock syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Wound infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Accidental overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood bilirubin increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>General physical condition abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hypovolaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Myositis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dupuytren's contracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Scleroderma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Seizure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Autoimmune encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Encephalitis autoimmune</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Leukoencephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Immune-mediated neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Brain oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dyskinesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Intracranial pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Nervous system disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Radiculopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Autoimmune nephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Bladder perforation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Interstitial lung disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dermatitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dermatitis exfoliative generalised</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pemphigoid</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Rash macular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Hysterectomy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hypotensive crisis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Orthostatic hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v23.1</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="173" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="209" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="18" subjects_affected="17" subjects_at_risk="216"/>
                <counts group_id="E2" events="50" subjects_affected="32" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperthyroidism</sub_title>
                <counts group_id="E1" events="22" subjects_affected="21" subjects_at_risk="216"/>
                <counts group_id="E2" events="10" subjects_affected="10" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" events="17" subjects_affected="17" subjects_at_risk="216"/>
                <counts group_id="E2" events="17" subjects_affected="15" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="22" subjects_affected="18" subjects_at_risk="216"/>
                <counts group_id="E2" events="29" subjects_affected="24" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="26" subjects_affected="20" subjects_at_risk="216"/>
                <counts group_id="E2" events="36" subjects_affected="32" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="58" subjects_affected="42" subjects_at_risk="216"/>
                <counts group_id="E2" events="293" subjects_affected="120" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="216"/>
                <counts group_id="E2" events="19" subjects_affected="18" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="32" subjects_affected="28" subjects_at_risk="216"/>
                <counts group_id="E2" events="61" subjects_affected="54" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" events="19" subjects_affected="14" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="16" subjects_affected="15" subjects_at_risk="216"/>
                <counts group_id="E2" events="53" subjects_affected="41" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="49" subjects_affected="42" subjects_at_risk="216"/>
                <counts group_id="E2" events="89" subjects_affected="59" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="54" subjects_affected="42" subjects_at_risk="216"/>
                <counts group_id="E2" events="64" subjects_affected="43" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="20" subjects_affected="17" subjects_at_risk="216"/>
                <counts group_id="E2" events="76" subjects_affected="50" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="19" subjects_affected="17" subjects_at_risk="216"/>
                <counts group_id="E2" events="87" subjects_affected="65" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" events="24" subjects_affected="15" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" events="12" subjects_affected="11" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="216"/>
                <counts group_id="E2" events="18" subjects_affected="13" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="15" subjects_affected="10" subjects_at_risk="216"/>
                <counts group_id="E2" events="13" subjects_affected="12" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" events="14" subjects_affected="13" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="19" subjects_affected="18" subjects_at_risk="216"/>
                <counts group_id="E2" events="42" subjects_affected="30" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" events="10" subjects_affected="9" subjects_at_risk="216"/>
                <counts group_id="E2" events="29" subjects_affected="19" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="20" subjects_affected="18" subjects_at_risk="216"/>
                <counts group_id="E2" events="57" subjects_affected="42" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" events="16" subjects_affected="13" subjects_at_risk="216"/>
                <counts group_id="E2" events="127" subjects_affected="81" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="216"/>
                <counts group_id="E2" events="19" subjects_affected="15" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" events="18" subjects_affected="15" subjects_at_risk="216"/>
                <counts group_id="E2" events="51" subjects_affected="28" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="13" subjects_affected="12" subjects_at_risk="216"/>
                <counts group_id="E2" events="13" subjects_affected="11" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="18" subjects_affected="16" subjects_at_risk="216"/>
                <counts group_id="E2" events="35" subjects_affected="30" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="13" subjects_affected="11" subjects_at_risk="216"/>
                <counts group_id="E2" events="23" subjects_affected="19" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="48" subjects_affected="37" subjects_at_risk="216"/>
                <counts group_id="E2" events="23" subjects_affected="21" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="29" subjects_affected="19" subjects_at_risk="216"/>
                <counts group_id="E2" events="17" subjects_affected="12" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="12" subjects_affected="12" subjects_at_risk="216"/>
                <counts group_id="E2" events="20" subjects_affected="18" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="9" subjects_affected="8" subjects_at_risk="216"/>
                <counts group_id="E2" events="12" subjects_affected="11" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="11" subjects_affected="8" subjects_at_risk="216"/>
                <counts group_id="E2" events="23" subjects_affected="18" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="19" subjects_affected="17" subjects_at_risk="216"/>
                <counts group_id="E2" events="36" subjects_affected="30" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="216"/>
                <counts group_id="E2" events="12" subjects_affected="11" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="27" subjects_affected="23" subjects_at_risk="216"/>
                <counts group_id="E2" events="26" subjects_affected="21" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="20" subjects_affected="19" subjects_at_risk="216"/>
                <counts group_id="E2" events="24" subjects_affected="18" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" events="68" subjects_affected="50" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" events="15" subjects_affected="14" subjects_at_risk="216"/>
                <counts group_id="E2" events="21" subjects_affected="15" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" events="12" subjects_affected="9" subjects_at_risk="216"/>
                <counts group_id="E2" events="20" subjects_affected="16" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" events="42" subjects_affected="35" subjects_at_risk="216"/>
                <counts group_id="E2" events="64" subjects_affected="44" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="37" subjects_affected="27" subjects_at_risk="216"/>
                <counts group_id="E2" events="154" subjects_affected="90" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="7" subjects_affected="5" subjects_at_risk="216"/>
                <counts group_id="E2" events="39" subjects_affected="26" subjects_at_risk="220"/>
              </event>
              <event>
                <sub_title>Vitiligo</sub_title>
                <counts group_id="E1" events="20" subjects_affected="19" subjects_at_risk="216"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="220"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="21" subjects_affected="15" subjects_at_risk="216"/>
                <counts group_id="E2" events="29" subjects_affected="24" subjects_at_risk="220"/>
              </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>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>1-800-821-8590</phone>
      <email>genentech@druginfo.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/NCT03273153
org study id: CO39722
secondary id: 2016-004387-18
nct id: NCT03273153
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase III, multicenter, open-label, randomized study designed to evaluate the
      efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with
      pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)
time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
description: PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
measure: PFS as Determined by the Investigator
time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
description: PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
measure: Objective Response as Determined by the Investigator
time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
description: Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions >/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis).
measure: Objective Response as Determined by IRC
time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
description: Objective response, defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by IRC according to RECIST v1.1
measure: Disease Control Rate (DCR)
time frame: Week 16
description: DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to <10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
measure: Overall Survival (OS)
time frame: From randomization up to approximately 3 years
description: OS is defined as the time from randomization to death from any cause.
measure: Duration of Objective Response Determined by the IRC
time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
description: Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.
measure: Duration of Objective Response Determined by the Investigator
time frame: Up to 3 years
description: Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.
measure: Two-year Landmark Survival
time frame: At 2 years
description: Two-year landmark survival is defined as the rate of survival at 2 years. Two-year landmark survival is defined as the rate of survival at 2 years and was calculated using Kaplan-Meier analysis, which is commonly used to estimate the probability of an event at time 't.'
measure: Change From Baseline in Health-related Quality of Life (HRQoL) Scores
time frame: Up to approximately 16 months. Follow up is reported at weeks after participant treatment discontinuation, which could occur at any time during the study. Total time frame does not exceed 16 months.
description: HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher ("better") level of functioning.
measure: Number of Participants With Adverse Events (AEs)
time frame: Up to approximately 16 months
description: An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
measure: Number of Participants With Abnormal Vital Signs
time frame: From baseline up to approximately 3 years
description: Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
measure: Number of Participants With Laboratory Abnormalities
time frame: Up to approximately 16 months
description: Participants with laboratory abnormalities (values outside of a defined range) will be reported.
measure: Plasma Concentration of Cobimetinib
time frame: Days 1 and 15 of Cycle 1
measure: Serum Concentration of Atezolizumab
time frame: Day 1 of Cycles 1, 2, and 3
measure: Percentage of Participants With Anti-drug Antibodies (ADAs)
time frame: Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation
description: Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.
arm group label: Cobimetinib and Atezolizumab
arm group type: Experimental
description: Participants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle.
arm group label: Pembrolizumab
arm group type: Active Comparator
description: Participants will receive 200 mg of pembrolizumab administered by IV infusion every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.
intervention type: Drug
intervention name: Cobimetinib
description: Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.
arm group label: Cobimetinib and Atezolizumab
intervention type: Drug
intervention name: Atezolizumab
description: Atezolizumab 840 mg as IV infusion once in every 2 weeks.
arm group label: Cobimetinib and Atezolizumab
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab 200 mg as IV infusion once in every 3 weeks.
arm group label: Pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Chair
affiliation: Hoffmann-La Roche
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country: Australia
country: Belgium
country: Brazil
country: France
country: Germany
country: Greece
country: Hungary
country: Italy
country: Korea, Republic of
country: Netherlands
country: Poland
country: Russian Federation
country: Spain
country: United Kingdom
country: United States
country: Canada
country: New Zealand
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Pembrolizumab
mesh term: Atezolizumab
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