<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/NCT03797326</url>
  </required_header>
  <id_info>
    <org_study_id>7902-005</org_study_id>
    <secondary_id>MK-7902-005</secondary_id>
    <secondary_id>E7080-G000-224</secondary_id>
    <secondary_id>LEAP-005</secondary_id>
    <secondary_id>2018-003747-37</secondary_id>
    <nct_id>NCT03797326</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) in Previously Treated Participants With Select Solid Tumors (MK-7902-005/E7080-G000-224/LEAP-005)</brief_title>
  <official_title>A Multicenter, Open-label Phase 2 Study of Lenvatinib (E7080/MK-7902) Plus Pembrolizumab (MK-3475) in Previously Treated Subjects With Selected Solid Tumors (LEAP-005)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eisai Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the safety and efficacy of combination therapy with&#xD;
      pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative&#xD;
      breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma&#xD;
      (GBM), biliary tract cancers (BTC), or pancreatic cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 12, 2019</start_date>
  <completion_date type="Anticipated">December 22, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 22, 2023</primary_completion_date>
  <phase>Phase 2</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>Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Glioblastoma (GBM) by Investigator Assessment in Initial Cohorts</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) as assessed by the investigator per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For participants with GBM, response will be assessed by the investigator based on RANO criteria (CR: disappearance of all target lesions, PR: sum of products of diameters [SPD] decreased by ≥ 50% from baseline value). For participants in the pancreatic cancer cohort, response will be assessed by blinded independent central review (BICR).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>ORR per RECIST 1.1 or RANO (GBM) by Blinded Independent Central Review (BICR) in Expanded Cohorts (Combined with Initial Cohorts)</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>ORR is defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For participants with GBM, response will be assessed based on RANO criteria (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Experience an Adverse Event (AE)</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving pembrolizumab plus lenvatinib who experience at least one AE will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Discontinue Study Treatment Due to an AE</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving pembrolizumab plus lenvatinib who discontinue study treatment due to an AE will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Receiving Lenvatinib Monotherapy who Experience an AE</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving lenvatinib monotherapy who experience at least one AE will be reported.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Receiving Lenvatinib Monotherapy who Discontinue Study Treatment Due to an Adverse Event (AE)</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving lenvatinib monotherapy who discontinue study treatment due to an AE will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) per RECIST 1.1 by Investigator Assessment in Initial Cohorts</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DCR will be assessed by the investigator for all initial cohorts except for the pancreatic cancer cohort, will be assessed by BICR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR will be assessed by the investigator for all initial cohorts except for the pancreatic cancer cohort, will be assessed by BICR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first. PFS will be assessed by the investigator for all initial cohorts except for the pancreatic cancer cohort, will be assessed by BICR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) in Initial Cohorts</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>OS is defined as the time from the date of study treatment to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR per RECIST 1.1 by BICR in Expanded Cohorts (Combined with Initial Cohorts)</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>DCR is defined as the percentage of participants who have a best overall response of CR, PR, or (SD) per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts)</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts)</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first, as assessed by BICR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS in Expanded Cohorts (Combined with Initial Cohorts)</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>OS is defined as the time from the date of study treatment to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>ORR is defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DCR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>DCR is defined as the percentage of participants who have a best overall response of CR, PR, or SD per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first, as assessed by BICR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS in Lenvatinib Monotherapy Arm</measure>
    <time_frame>Up to approximately 72 months</time_frame>
    <description>OS is defined as the time from the date of study treatment to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma Concentration of Lenvatinib</measure>
    <time_frame>Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose (up to approximately 23 days). Each cycle is 21 days.</time_frame>
    <description>Blood samples will be obtained on Day 1 and Day 15 of Cycle 1 (21-day cycle) and Day 1 of Cycle 2 (21-day cycle) for pharmacokinetic (PK) analysis to determine the plasma concentration of lenvatinib.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">590</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <condition>Triple Negative Breast Cancer</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Gastric Cancer</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Glioblastoma</condition>
  <condition>Biliary Tract Cancers</condition>
  <condition>Pancreatic Cancer</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab + Lenvatinib (Arm 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib 20 mg via oral capsule once a day (QD). Pembrolizumab will be administered for up to 35 cycles (up to 2 years). Lenvatinib will be administered until progressive disease or unacceptable toxicity (up to at least 2 years).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Lenvatinib Monotherapy (Arm 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive lenvatinib 24 mg via oral capsule QD, to be administered until progressive disease or unacceptable toxicity (up to at least 2 years).</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Administered as an IV infusion on Day 1 Q3W.</description>
    <arm_group_label>Pembrolizumab + Lenvatinib (Arm 1)</arm_group_label>
    <other_name>MK-3475</other_name>
    <other_name>Keytruda®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lenvatinib</intervention_name>
    <description>Administered orally once a day during each 21-day cycle.</description>
    <arm_group_label>Lenvatinib Monotherapy (Arm 2)</arm_group_label>
    <arm_group_label>Pembrolizumab + Lenvatinib (Arm 1)</arm_group_label>
    <other_name>MK-7902</other_name>
    <other_name>E7080</other_name>
    <other_name>LENVIMA™</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has a histologically or cytologically-documented, advanced (metastatic and/or&#xD;
             unresectable) solid tumor that is incurable and for which prior standard systemic&#xD;
             therapy has failed in one of the following cohorts: TNBC, Ovarian Cancer, Gastric&#xD;
             Cancer, Colorectal Cancer, GBM, BTC (intrahepatic, extrahepatic cholangiocarcinoma and&#xD;
             gall bladder cancer; excludes Ampulla of Vater), Pancreatic Cancer&#xD;
&#xD;
          -  Must have progressed on or since the last treatment&#xD;
&#xD;
          -  Has measurable disease per RECIST 1.1 (RANO for the GBM cohort) as assessed by the&#xD;
             local site investigator/radiology and confirmed by BICR&#xD;
&#xD;
          -  Has provided a PD-L1 evaluable archival tumor tissue sample or newly obtained core or&#xD;
             excisional biopsy of a tumor lesion not previously irradiated&#xD;
&#xD;
          -  Male participants agree to use approved contraception during the treatment period for&#xD;
             at least 7 days after the last dose of lenvatinib, or refrain from heterosexual&#xD;
             intercourse during this period&#xD;
&#xD;
          -  Female participants are not pregnant or breastfeeding, and are not a woman of&#xD;
             childbearing potential (WOCBP), OR are a WOCBP that agrees to use contraception during&#xD;
             the treatment period (or 14 days prior to the initiation of study treatment for oral&#xD;
             contraception) and for at least 120 days post pembrolizumab, or 30 days post&#xD;
             lenvatinib, whichever occurs last&#xD;
&#xD;
          -  Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3&#xD;
             days of study treatment initiation&#xD;
&#xD;
          -  Has adequate organ function&#xD;
&#xD;
        For Triple Negative Breast Cancer Participants:&#xD;
&#xD;
          -  Has received one or 2 prior lines of therapy&#xD;
&#xD;
          -  Has Lactate Dehydrogenase (LDH) &lt;2.0 x Upper Limit of Normal (ULN)&#xD;
&#xD;
          -  Has locally determined results for estrogen receptor, progesterone receptor, and human&#xD;
             epidermal growth factor receptor 2 tumor analyses&#xD;
&#xD;
        For Ovarian Cancer Participants:&#xD;
&#xD;
        - Has primary ovarian cancer and has received 3 prior lines of therapy.&#xD;
&#xD;
        For Gastric Cancer Participants:&#xD;
&#xD;
        - Has received 2 prior lines of therapy. Note: Gastric cancer will include participants&#xD;
        with both gastric and gastroesophageal junction (GEJ) adenocarcinoma. Participants with&#xD;
        squamous cell carcinoma histology are not eligible&#xD;
&#xD;
        For Colorectal Cancer Participants:&#xD;
&#xD;
        - Has received 2 prior lines of therapy&#xD;
&#xD;
        For GBM Participants:&#xD;
&#xD;
          -  Has failed initial systemic therapy for newly diagnosed GBM&#xD;
&#xD;
          -  Have the following time periods elapsed before the projected start of scheduled study&#xD;
             treatment: 1) at least 3 weeks from prior surgical resection, 2) at least 1 week from&#xD;
             stereotactic biopsy, 3) at least 6 months from completion of prior radiotherapy, 4) at&#xD;
             least 4 weeks (or 5 half-lives, whichever is shorter) from any investigational agent,&#xD;
             5) at least 4 weeks from cytotoxic therapy, 6) at least 6 weeks from antibodies, 7) at&#xD;
             least 4 weeks (or 5 half-lives, whichever is shorter) from other antitumor therapies&#xD;
             and 1 week for cancer vaccines&#xD;
&#xD;
          -  Be neurologically stable (e.g. without a progression of neurologic symptoms or&#xD;
             requiring escalating doses of systemic steroid therapy within last 2 weeks) and&#xD;
             clinically stable&#xD;
&#xD;
          -  Has histologically confirmed World Health Organization (WHO) Grade IV GBM&#xD;
&#xD;
          -  Has locally determined result for O^6-methylguanine-DNA methyltransferase (MGMT)&#xD;
             analysis&#xD;
&#xD;
        For Biliary Tract Cancer Participants:&#xD;
&#xD;
          -  Has received 1 prior line of therapy&#xD;
&#xD;
          -  Child-Pugh Score, Class A: well-compensated disease. Child-Pugh Score of 5-6&#xD;
&#xD;
        For Pancreatic Cancer Participants:&#xD;
&#xD;
          -  Has pathologically (histologically or cytologically) confirmed pancreatic ductal&#xD;
             adenocarcinoma that is metastatic at enrollment&#xD;
&#xD;
          -  Has received one or 2 prior lines of therapy&#xD;
&#xD;
          -  Has received prior therapy with at least 1 (platinum-containing regimen or&#xD;
             gemcitabine-containing regimen) but no more than 2 prior systemic therapies for&#xD;
             unresectable or metastatic pancreatic cancer&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has gastrointestinal malabsorption or any other condition that might affect the&#xD;
             absorption of lenvatinib&#xD;
&#xD;
          -  Has present or progressive accumulation of pleural, ascitic, or pericardial fluid&#xD;
             requiring drainage or diuretic drugs within 2 weeks prior to enrollment (applies to&#xD;
             all cohorts except the ovarian cancer cohort)&#xD;
&#xD;
          -  Has radiographic evidence of encasement or invasion of a major blood vessel or of&#xD;
             intratumoral cavitation. Participants with portal vein invasion (Vp4), inferior vena&#xD;
             cava, or cardiac involvement based on imaging in the BTC cohort are not eligible for&#xD;
             enrollment&#xD;
&#xD;
          -  Has clinical significant hemoptysis or tumor bleeding within 2 weeks prior to the&#xD;
             first dose of study treatment&#xD;
&#xD;
          -  Has significant cardiovascular impairment within 12 months of the first dose of study&#xD;
             treatment, such as history of congestive heart failure greater than New York Heart&#xD;
             Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular&#xD;
             accident (CVA), or cardiac arrhythmia associated with hemodynamic instability&#xD;
&#xD;
          -  Has a history of arterial thromboembolism within 12 months of start of study treatment&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or has required active treatment&#xD;
             within the past 3 years.&#xD;
&#xD;
          -  Has a serious nonhealing wound, ulcer or bone fracture&#xD;
&#xD;
          -  Has had major surgery within 3 weeks prior to first dose of study interventions&#xD;
&#xD;
          -  Has biologic response modifiers therapy (e.g. granulocyte colony-stimulating factor)&#xD;
             within 4 weeks before study entry&#xD;
&#xD;
          -  Has preexisting ≥Grade 3 gastrointestinal (GI) or non-gastrointestinal fistula&#xD;
&#xD;
          -  Has received prior therapy with lenvatinib, an anti-PD-1, anti-PD-L1, or anti PD-L2&#xD;
             agent or with an agent directed to another stimulatory or co-inhibitory T-cell&#xD;
             receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis&#xD;
             factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor&#xD;
             superfamily member 9 [CD137])&#xD;
&#xD;
          -  Has received prior systemic anti-cancer therapy including investigational agents&#xD;
             within 4 weeks prior to study treatment start&#xD;
&#xD;
          -  If participant received major surgery, they must have recovered adequately from the&#xD;
             toxicity and/or complications from the intervention prior to starting study treatment&#xD;
&#xD;
          -  Has received prior radiotherapy within 2 weeks of start of study treatment.&#xD;
             Participants must have recovered from all radiation-related toxicities, not require&#xD;
             corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted&#xD;
             for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system&#xD;
             (CNS) disease&#xD;
&#xD;
          -  Has received a live vaccine within 30 days prior to the first dose of study treatment&#xD;
&#xD;
          -  Has known intolerance to lenvatinib (and/or any of the excipients)&#xD;
&#xD;
          -  Is currently participating in or has participated in a study of an investigational&#xD;
             agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
             study treatment&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior the first dose of study treatment&#xD;
&#xD;
          -  Has known active CNS metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  Has tumors involving the brain stem&#xD;
&#xD;
          -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients&#xD;
&#xD;
          -  Has an active autoimmune disease that has required systemic treatment in past 2 years&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or has current&#xD;
             pneumonitis&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Has a known history of hepatitis B or known active hepatitis C virus infection&#xD;
&#xD;
          -  Has a known history of active tuberculosis (TB; Bacillus tuberculosis)&#xD;
&#xD;
          -  Is pregnant or breastfeeding or expecting to conceive or father children within the&#xD;
             projected duration of the study, starting with the screening visit through 120 days&#xD;
             after the last dose of study treatment&#xD;
&#xD;
          -  Has had an allogenic tissue/solid organ transplant (large organ transplants, stem-cell&#xD;
             transplant requiring chronic immunosuppressant therapy necessary to prevent graft&#xD;
             rejection)&#xD;
&#xD;
        For GBM Participants:&#xD;
&#xD;
          -  Has carcinomatous meningitis&#xD;
&#xD;
          -  Has recurrent tumor greater than 6 cm in maximum diameter&#xD;
&#xD;
          -  Has tumor primarily localized to the brainstem or spinal cord&#xD;
&#xD;
          -  Has presence of multifocal tumor, diffuse leptomeningeal or extracranial disease&#xD;
&#xD;
          -  Has evidence of intratumoral or peritumoral hemorrhage on baseline magnetic resonance&#xD;
             imaging (MRI) scan other than those that are grade ≤ 1 and either post-operative or&#xD;
             stable on at least 2 consecutive MRI scans&#xD;
&#xD;
          -  Has received Optune® TTFields within 2 weeks of study intervention&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope ( Site 0002)</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars Sinai Medical Center ( Site 0003)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center ( Site 0005)</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado, Anschutz Cancer Pavilion ( Site 0007)</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida-Health Cancer Center-Orlando ( Site 0015)</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey ( Site 0009)</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laura and Isaac Perlmutter Cancer Center at NYU Langone Health ( Site 0023)</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Fargo Medical Center ( Site 0059)</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lehigh Valley Hospital- Cedar Crest ( Site 0047)</name>
      <address>
        <city>Allentown</city>
        <state>Pennsylvania</state>
        <zip>18103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Cancer Center ( Site 0058)</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Cancer Center - East Campus ( Site 0018)</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Cancer Research Centers - Medical City Hospital ( Site 0049)</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Medical Center ( Site 0021)</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin Carbone Cancer Center ( Site 0017)</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792-0001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Favaloro para la Docencia e Investigacion Medica ( Site 2106)</name>
      <address>
        <city>Ciudad Autonoma de Buenos Aires</city>
        <state>Buenos Aires</state>
        <zip>C1078AAI</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Aleman ( Site 2100)</name>
      <address>
        <city>Buenos Aires</city>
        <state>Caba</state>
        <zip>1118</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Britanico de Buenos Aires ( Site 2109)</name>
      <address>
        <city>Ciudad de Buenos Aires</city>
        <state>Caba</state>
        <zip>C1280AEB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Oncologia de Rosario ( Site 2105)</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>S2000KZE</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CEMIC ( Site 2104)</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1431FWO</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IDIM Instituto de Diagnostico e Investigaciones Metabolicas ( Site 2101)</name>
      <address>
        <city>Caba</city>
        <zip>C1012AAR</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Brisbane and Women s Hospital ( Site 0901)</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alfred Health ( Site 0902)</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sir Charles Gairdner Hospital ( Site 0903)</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BC Cancer - Abbotsford ( Site 0200)</name>
      <address>
        <city>Abbotsford</city>
        <state>British Columbia</state>
        <zip>V2S 0C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CancerCare Manitoba ( Site 0201)</name>
      <address>
        <city>Winnipeg</city>
        <state>Manitoba</state>
        <zip>R3E 0V9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0208)</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 4X2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Research Institute ( Site 0207)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M4N 3M5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre ( Site 0202)</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0210)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 3E4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Quebec Universite de Laval ( Site 0206)</name>
      <address>
        <city>Quebec</city>
        <zip>G1R 2J6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Investigación del Cáncer James Lind ( Site 1203)</name>
      <address>
        <city>Temuco</city>
        <state>Araucania</state>
        <zip>4780000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Arturo Lopez Perez ( Site 1201)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>7500921</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pontificia Universidad Catolica de Chile ( Site 1202)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>8330024</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universidad de Chile ( Site 1200)</name>
      <address>
        <city>Santiago</city>
        <state>Region M. De Santiago</state>
        <zip>8380456</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Colombiana de Cancerologia Clinica Vida ( Site 1105)</name>
      <address>
        <city>Medellin</city>
        <state>Antioquia</state>
        <zip>050030</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Nacional de Cancerologia E.S.E ( Site 1102)</name>
      <address>
        <city>Bogota</city>
        <state>Distrito Capital De Bogota</state>
        <zip>110321</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncologos del Occidente S.A. ( Site 1106)</name>
      <address>
        <city>Pereira</city>
        <state>Risaralda</state>
        <zip>660001</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fundacion Valle del Lili ( Site 1101)</name>
      <address>
        <city>Cali</city>
        <state>Valle Del Cauca</state>
        <zip>760032</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Antoine Lacassagne ( Site 0404)</name>
      <address>
        <city>Nice</city>
        <state>Alpes-Maritimes</state>
        <zip>06189</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard ( Site 0405)</name>
      <address>
        <city>Lyon</city>
        <state>Auvergne</state>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Claudius Regaud IUCT Oncopole ( Site 0403)</name>
      <address>
        <city>Toulouse</city>
        <state>Haute-Garonne</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Oscar Lambret ( Site 0401)</name>
      <address>
        <city>Lille</city>
        <state>Nord</state>
        <zip>59000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut de Cancerologie de l Ouest Centre Rene Gauducheau ( Site 0402)</name>
      <address>
        <city>Saint-Herblain</city>
        <state>Val-de-Marne</state>
        <zip>44805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy ( Site 0400)</name>
      <address>
        <city>Villejuif</city>
        <state>Val-de-Marne</state>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Robert Bosch GmbH ( Site 0307)</name>
      <address>
        <city>Stuttgart</city>
        <state>Baden-Wurttemberg</state>
        <zip>70376</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Regensburg ( Site 0304)</name>
      <address>
        <city>Regensburg</city>
        <state>Bayern</state>
        <zip>93053</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Frankfurt ( Site 0306)</name>
      <address>
        <city>Frankfurt am Main</city>
        <state>Hessen</state>
        <zip>60528</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 0301)</name>
      <address>
        <city>Wiesbaden</city>
        <state>Hessen</state>
        <zip>65199</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SRH Wald-Klinikum Gera GmbH ( Site 0309)</name>
      <address>
        <city>Gera</city>
        <state>Thuringen</state>
        <zip>07548</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Jena ( Site 0302)</name>
      <address>
        <city>Jena</city>
        <state>Thuringen</state>
        <zip>07740</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soroka Medical Center ( Site 0601)</name>
      <address>
        <city>Beer Sheva</city>
        <zip>8457108</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rambam Medical Center ( Site 0602)</name>
      <address>
        <city>Haifa</city>
        <zip>3109601</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hadassah Ein Kerem Medical Center ( Site 0604)</name>
      <address>
        <city>Jerusalem</city>
        <zip>9112001</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chaim Sheba Medical Center ( Site 0600)</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5262000</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sourasky Medical Center ( Site 0603)</name>
      <address>
        <city>Tel Aviv</city>
        <zip>6423906</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Clinico Humanitas Research Hospital ( Site 1402)</name>
      <address>
        <city>Rozzano</city>
        <state>Milano</state>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinico Le Scotte - A.O. Senese ( Site 1401)</name>
      <address>
        <city>Siena</city>
        <state>Toscana</state>
        <zip>53100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Fondazione Pascale ( Site 1400)</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fondazione Policlinico Universitario A. Gemelli ( Site 1403)</name>
      <address>
        <city>Roma</city>
        <zip>00168</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center ( Site 1002)</name>
      <address>
        <city>Songpagu</city>
        <state>Seoul</state>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital ( Site 1000)</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 ( Site 1001)</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arkhangelsk Clinical Oncological Dispensary ( Site 1600)</name>
      <address>
        <city>Arkhangelsk</city>
        <state>Arkhangel Skaya Oblast</state>
        <zip>163045</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Russian Oncological Research Center n.a. N.N. Blokhin ( Site 1604)</name>
      <address>
        <city>Moscow</city>
        <state>Moskva</state>
        <zip>115478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leningrad Regional Oncology Center ( Site 1609)</name>
      <address>
        <city>Saint-Petersburg</city>
        <state>Sankt-Peterburg</state>
        <zip>188663</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1610)</name>
      <address>
        <city>Saint-Petersburg</city>
        <state>Sankt-Peterburg</state>
        <zip>197758</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City Clinical Oncology Center ( Site 1608)</name>
      <address>
        <city>Saint-Petersburg</city>
        <state>Sankt-Peterburg</state>
        <zip>198255</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1603)</name>
      <address>
        <city>Kazan</city>
        <state>Tatarstan, Respublika</state>
        <zip>420029</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic i Provincial ( Site 0703)</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Gregorio Maranon ( Site 0701)</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universitaria de Navarra ( Site 0704)</name>
      <address>
        <city>Madrid</city>
        <zip>28027</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramon y Cajal ( Site 0702)</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inselspital Universitaetsspital Bern ( Site 1705)</name>
      <address>
        <city>Bern</city>
        <state>Berne</state>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital Graubuenden ( Site 1704)</name>
      <address>
        <city>Chur</city>
        <state>Grisons</state>
        <zip>7000</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kantonsspital St. Gallen ( Site 1702)</name>
      <address>
        <city>St. Gallen</city>
        <state>Sankt Gallen</state>
        <zip>9007</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ospedale Regionale di Bellinzona e Valli ( Site 1703)</name>
      <address>
        <city>Bellinzona</city>
        <state>Ticino</state>
        <zip>6500</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopitaux Universitaires de Geneve HUG ( Site 1701)</name>
      <address>
        <city>Geneve</city>
        <zip>1211</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsspital Zurich ( Site 1700)</name>
      <address>
        <city>Zurich</city>
        <zip>8091</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cheng Kung University Hospital ( Site 3003)</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital ( Site 3000)</name>
      <address>
        <city>Taipei</city>
        <zip>10002</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chulalongkorn University ( Site 5001)</name>
      <address>
        <city>Bangkok</city>
        <state>Krung Thep Maha Nakhon</state>
        <zip>10330</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ramathibodi Hospital. ( Site 5002)</name>
      <address>
        <city>Bangkok</city>
        <state>Krung Thep Maha Nakhon</state>
        <zip>10400</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siriraj Hospital ( Site 5003)</name>
      <address>
        <city>Bangkok</city>
        <state>Krung Thep Maha Nakhon</state>
        <zip>10700</zip>
        <country>Thailand</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Trust ( Site 0803)</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Leicester Royal Infirmary. Univ. Hosp. of Leicester NHS Trust ( Site 0804)</name>
      <address>
        <city>Leicester</city>
        <state>Leicestershire</state>
        <zip>LE1 5WW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guy's Hospital ( Site 0806)</name>
      <address>
        <city>London</city>
        <state>London, City Of</state>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital (Sutton) ( Site 0800)</name>
      <address>
        <city>London</city>
        <state>Surrey</state>
        <zip>SM3 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christie NHS Foundation Trust ( Site 0805)</name>
      <address>
        <city>Manchester</city>
        <zip>M20 4BX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Canada</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Israel</country>
    <country>Italy</country>
    <country>Korea, Republic of</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Switzerland</country>
    <country>Taiwan</country>
    <country>Thailand</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trial Information</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 7, 2019</study_first_submitted>
  <study_first_submitted_qc>January 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>August 19, 2022</last_update_submitted>
  <last_update_submitted_qc>August 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>programmed cell death 1 (PD-1, PD1)</keyword>
  <keyword>programmed cell death ligand 1 (PD-L1, PDL1)</keyword>
  <keyword>programmed cell death ligand 2 (PD-L2, PDL2)</keyword>
  <keyword>tyrosine kinase inhibitor (TKI)</keyword>
  <keyword>multiple TKI</keyword>
  <keyword>Vascular Endothelial Growth Factor Receptor (VEFG)</keyword>
  <keyword>Fibroblast Growth Factor (FGF)</keyword>
  <keyword>Platelet-Derived Growth Factor (PDGF)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glioblastoma</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
    <mesh_term>Biliary Tract Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Lenvatinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03797326
org study id: 7902-005
secondary id: MK-7902-005
secondary id: E7080-G000-224
secondary id: LEAP-005
secondary id: 2018-003747-37
nct id: NCT03797326
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to determine the safety and efficacy of combination therapy with
      pembrolizumab (MK-3475) and lenvatinib (E7080/MK-7902) in participants with triple negative
      breast cancer (TNBC), ovarian cancer, gastric cancer, colorectal cancer (CRC), glioblastoma
      (GBM), biliary tract cancers (BTC), or pancreatic cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) or Response Assessment in Neuro-Oncology (RANO) Criteria for Glioblastoma (GBM) by Investigator Assessment in Initial Cohorts
time frame: Up to approximately 72 months
description: ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) as assessed by the investigator per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For participants with GBM, response will be assessed by the investigator based on RANO criteria (CR: disappearance of all target lesions, PR: sum of products of diameters [SPD] decreased by ≥ 50% from baseline value). For participants in the pancreatic cancer cohort, response will be assessed by blinded independent central review (BICR).
measure: ORR per RECIST 1.1 or RANO (GBM) by Blinded Independent Central Review (BICR) in Expanded Cohorts (Combined with Initial Cohorts)
time frame: Up to approximately 72 months
description: ORR is defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. For participants with GBM, response will be assessed based on RANO criteria (CR: disappearance of all target lesions, PR: SPD decreased by ≥ 50% from baseline value).
measure: Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Experience an Adverse Event (AE)
time frame: Up to approximately 72 months
description: An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving pembrolizumab plus lenvatinib who experience at least one AE will be reported.
measure: Percentage of Participants Receiving Pembrolizumab Plus Lenvatinib who Discontinue Study Treatment Due to an AE
time frame: Up to approximately 72 months
description: An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving pembrolizumab plus lenvatinib who discontinue study treatment due to an AE will be reported.
measure: Percentage of Participants Receiving Lenvatinib Monotherapy who Experience an AE
time frame: Up to approximately 72 months
description: An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving lenvatinib monotherapy who experience at least one AE will be reported.
measure: Percentage of Participants Receiving Lenvatinib Monotherapy who Discontinue Study Treatment Due to an Adverse Event (AE)
time frame: Up to approximately 72 months
description: An AE is any untoward medical occurrence in a clinical study participant that is temporally associated with the use of study treatment, whether or not considered related to the study treatment. The percentage of participants receiving lenvatinib monotherapy who discontinue study treatment due to an AE will be reported.
measure: Disease Control Rate (DCR) per RECIST 1.1 by Investigator Assessment in Initial Cohorts
time frame: Up to approximately 72 months
description: DCR is defined as the percentage of participants who have a best overall response of CR, PR, or stable disease (SD) per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DCR will be assessed by the investigator for all initial cohorts except for the pancreatic cancer cohort, will be assessed by BICR.
measure: Duration of Response (DOR) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts
time frame: Up to approximately 72 months
description: DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. DOR will be assessed by the investigator for all initial cohorts except for the pancreatic cancer cohort, will be assessed by BICR.
measure: Progression Free Survival (PFS) per RECIST 1.1 or RANO (GBM) by Investigator Assessment in Initial Cohorts
time frame: Up to approximately 72 months
description: PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first. PFS will be assessed by the investigator for all initial cohorts except for the pancreatic cancer cohort, will be assessed by BICR.
measure: Overall Survival (OS) in Initial Cohorts
time frame: Up to approximately 72 months
description: OS is defined as the time from the date of study treatment to the date of death due to any cause.
measure: DCR per RECIST 1.1 by BICR in Expanded Cohorts (Combined with Initial Cohorts)
time frame: Up to approximately 72 months
description: DCR is defined as the percentage of participants who have a best overall response of CR, PR, or (SD) per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.
measure: DOR per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts)
time frame: Up to approximately 72 months
description: DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.
measure: PFS per RECIST 1.1 or RANO (GBM) by BICR in Expanded Cohorts (Combined with Initial Cohorts)
time frame: Up to approximately 72 months
description: PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first, as assessed by BICR.
measure: OS in Expanded Cohorts (Combined with Initial Cohorts)
time frame: Up to approximately 72 months
description: OS is defined as the time from the date of study treatment to the date of death due to any cause.
measure: ORR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
time frame: Up to approximately 72 months
description: ORR is defined as the percentage of participants who have a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD) as assessed by BICR per RECIST 1.1, which is modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.
measure: DCR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
time frame: Up to approximately 72 months
description: DCR is defined as the percentage of participants who have a best overall response of CR, PR, or SD per RECIST 1.1. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.
measure: DOR per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
time frame: Up to approximately 72 months
description: DOR is determined by disease assessment and is defined as the time from the earliest date of qualifying response until earliest date of disease progression or death from any cause, whichever comes first. RECIST 1.1 has been modified for this study to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, and will be assessed by BICR for this outcome measure.
measure: PFS per RECIST 1.1 by BICR in Lenvatinib Monotherapy Arm
time frame: Up to approximately 72 months
description: PFS is defined as the time from date of study treatment to the first documented disease progression based on RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ (or RANO for GBM participants), or death due to any cause, whichever occurs first, as assessed by BICR.
measure: OS in Lenvatinib Monotherapy Arm
time frame: Up to approximately 72 months
description: OS is defined as the time from the date of study treatment to the date of death due to any cause.
measure: Plasma Concentration of Lenvatinib
time frame: Cycle 1 Day 1: 0.5-4 hours and 6-10 hours post-dose; Cycle 1 Day 15: pre-dose and 2-12 hours post-dose; Cycle 2 Day 1: pre-dose, 0.5-4 hours, and 6-10 hours post-dose (up to approximately 23 days). Each cycle is 21 days.
description: Blood samples will be obtained on Day 1 and Day 15 of Cycle 1 (21-day cycle) and Day 1 of Cycle 2 (21-day cycle) for pharmacokinetic (PK) analysis to determine the plasma concentration of lenvatinib.
arm group label: Pembrolizumab + Lenvatinib (Arm 1)
arm group type: Experimental
description: Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) plus lenvatinib 20 mg via oral capsule once a day (QD). Pembrolizumab will be administered for up to 35 cycles (up to 2 years). Lenvatinib will be administered until progressive disease or unacceptable toxicity (up to at least 2 years).
arm group label: Lenvatinib Monotherapy (Arm 2)
arm group type: Experimental
description: Participants receive lenvatinib 24 mg via oral capsule QD, to be administered until progressive disease or unacceptable toxicity (up to at least 2 years).
intervention type: Biological
intervention name: Pembrolizumab
description: Administered as an IV infusion on Day 1 Q3W.
arm group label: Pembrolizumab + Lenvatinib (Arm 1)
other name: MK-3475
other name: Keytruda®
intervention type: Drug
intervention name: Lenvatinib
description: Administered orally once a day during each 21-day cycle.
arm group label: Lenvatinib Monotherapy (Arm 2)
arm group label: Pembrolizumab + Lenvatinib (Arm 1)
other name: MK-7902
other name: E7080
other name: LENVIMA™
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
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country: Argentina
country: Australia
country: Canada
country: Chile
country: Colombia
country: France
country: Germany
country: Israel
country: Italy
country: Korea, Republic of
country: Russian Federation
country: Spain
country: Switzerland
country: Taiwan
country: Thailand
country: United Kingdom
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trial Information
responsible party type: Sponsor
mesh term: Glioblastoma
mesh term: Triple Negative Breast Neoplasms
mesh term: Biliary Tract Neoplasms
mesh term: Pembrolizumab
mesh term: Lenvatinib
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php