<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/NCT02972034</url>
  </required_header>
  <id_info>
    <org_study_id>8353-013</org_study_id>
    <secondary_id>MK-8353-013</secondary_id>
    <secondary_id>2016-003478-42</secondary_id>
    <nct_id>NCT02972034</nct_id>
  </id_info>
  <brief_title>Study of MK-8353 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Malignancies (MK-8353-013)</brief_title>
  <official_title>A Phase Ib Study to Evaluate the Safety and Tolerability of MK-8353 in Combination With Pembrolizumab in Patients With Advanced Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </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>
      This study will evaluate the safety, tolerability and preliminary efficacy of MK-8353 when&#xD;
      administered in combination with pembrolizumab (MK-3475). There are two parts in this study:&#xD;
      Part 1 will be dose escalation and confirmation, and Part 2 will be a cohort expansion. In&#xD;
      Part 1, the recommended phase II dose (RP2D) of MK-8353 in combination with a fixed dose of&#xD;
      pembrolizumab in participants with advanced malignancies will be identified and confirmed.&#xD;
      Participants will be initially enrolled to receive MK-8353 at 350 mg twice a day (BID) in&#xD;
      combination with pembrolizumab at a fixed dose of 200 mg on Day 1 of each 3-week cycle (Q3W)&#xD;
      for up to 24 months of treatment. In Part 2, participants with advanced colorectal cancer&#xD;
      (CRC) that is microsatellite stable (i.e., non-microsatellite instability-high/deficient&#xD;
      mismatch repair [non-MSI-H/dMMR]) who received at least one and up to five prior lines of&#xD;
      therapy will be enrolled at the RP2D in the expansion cohort to further evaluate safety and&#xD;
      efficacy.&#xD;
&#xD;
      The protocol has been amended to lower the starting doses of MK-8353 in combination with&#xD;
      pembrolizumab. In addition, 3 arms have been added: one in which MK-8353 will be administered&#xD;
      continuously once a day (QD) in combination with pembrolizumab, one optional arm in which&#xD;
      MK-8353 will be administered 1 week on/1 week off QD in combination with pembrolizumab and&#xD;
      one optional arm in which participants undergo a MK-8353 QD run-in period prior to starting&#xD;
      combination therapy with pembrolizumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 13, 2017</start_date>
  <completion_date type="Actual">December 2, 2022</completion_date>
  <primary_completion_date type="Actual">December 2, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Who Experience an Adverse Event (AE)</measure>
    <time_frame>Up to 27 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who Discontinue Study Drug Due to an AE</measure>
    <time_frame>Up to 24 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants Who Experience a Dose-limiting Toxicity (DLT)</measure>
    <time_frame>During Cycle 1 (Arms A, B &amp; C: Up to 21 days; Arm D: Up to 35 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by the Investigator</measure>
    <time_frame>Up to 24 months</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">110</enrollment>
  <condition>Neoplasms</condition>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>A: MK-8353 BID Continuous+Pembro</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive MK-8353 orally (PO) two times each day (BID) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab (pembro) 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 35 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B: MK-8353 QD Continuous+Pembro</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants receive MK-8353 PO once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>C: MK-8353 QD 1 Week On/1 Week Off+Pembro</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Optional Arm: Participants receive MK-8353 PO QD on Days 1 to 7, Days 15 to 21 and Days 29 to 35 PLUS pembrolizumab 200 mg IV on Day 1 and Day 22 of each 42-day period (based on 2 cycles of 21 days) for up to 35 cycles.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Optional Arm: Participants undergo an MK-8353 PO QD run-in period from Day -14 to Day -1 prior to Cycle 1 during which they receive MK-8353 PO QD. After the run-in period, participants receive MK-8353 PO QD on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 36 cycles.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MK-8353</intervention_name>
    <description>PO capsule</description>
    <arm_group_label>A: MK-8353 BID Continuous+Pembro</arm_group_label>
    <arm_group_label>B: MK-8353 QD Continuous+Pembro</arm_group_label>
    <arm_group_label>C: MK-8353 QD 1 Week On/1 Week Off+Pembro</arm_group_label>
    <arm_group_label>D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>IV infusion</description>
    <arm_group_label>A: MK-8353 BID Continuous+Pembro</arm_group_label>
    <arm_group_label>B: MK-8353 QD Continuous+Pembro</arm_group_label>
    <arm_group_label>C: MK-8353 QD 1 Week On/1 Week Off+Pembro</arm_group_label>
    <arm_group_label>D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro</arm_group_label>
    <other_name>MK-3475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Part 1: Has a histologically- or cytologically-documented, locally-advanced or&#xD;
             metastatic solid malignancy and has received ≥1 and &lt;6 prior line of cancer treatment&#xD;
             regimen(s).&#xD;
&#xD;
          -  Part 2: Has a histologically-confirmed adenocarcinoma originating from the colon or&#xD;
             rectum (Stage 4 American Joint Committee on Cancer [AJCC] 7th edition) that is&#xD;
             microsatellite stable (i.e., non-MSI-H/dMMR). Appendiceal cancer is included AND Has&#xD;
             experienced disease progression or was intolerant to at least 1 and up to 5 systemic&#xD;
             chemotherapy regimen(s) for metastatic CRC that must have included fluroropyrimidines&#xD;
             and irinotecan or oxaliplatin, ± anti-vascular endothelial growth factor (VEGF) or&#xD;
             anti-epidermal growth factor receptor (EGFR)(if indicated by RAS mutational status).&#xD;
&#xD;
          -  Provides an archival or newly obtained tumor tissue sample and blood samples for&#xD;
             biomarker analysis.&#xD;
&#xD;
          -  Has ≥1 measurable lesion as defined by RECIST 1.1 on imaging studies.&#xD;
&#xD;
          -  Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)&#xD;
             Performance Scale.&#xD;
&#xD;
          -  Has adequate organ function&#xD;
&#xD;
          -  Female participants of childbearing potential who are willing to use either 2 adequate&#xD;
             barrier methods, or to abstain from heterosexual activity throughout the study.&#xD;
&#xD;
          -  Male participants of childbearing potential must agree to use an adequate method of&#xD;
             contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has disease that is suitable for local treatment administered with curative intent.&#xD;
&#xD;
          -  Part 1: Has received prior therapy with cancer vaccines, or compounds targeting PD-1&#xD;
             (including Merck pembrolizumab [MK-3475]), programmed cell death ligand 1 (PD-L1),&#xD;
             PD-L2, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or Mitogen-activated&#xD;
             protein kinase (MAPK)/Extracellular signal-regulated Kinase (MEK).&#xD;
&#xD;
          -  Part 2: Has received prior therapy with cancer vaccines, or compounds targeting PD-1&#xD;
             (including Merck pembrolizumab [MK-3475]), PD-L1, PD-L2, CTLA-4, lymphocyte-activation&#xD;
             gene 3 (LAG-3), CD-137, OX-40 (tumor necrosis factor receptor superfamily, member 4&#xD;
             [TNFRSF4], also known as CD134), cluster of differentiation 40 (CD-40),&#xD;
             glucocorticoid-induced TNFR-related protein (GITR), serine/threonine-protein kinase&#xD;
             B-Raf (BRAF), MEK or other molecules in the MAPK pathway.&#xD;
&#xD;
          -  Is currently participating in or has participated in a study of an investigational&#xD;
             agent or using an investigational device within 4 weeks prior to the first dose of&#xD;
             study drug.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
             (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
&#xD;
          -  Has had a prior anticancer monoclonal antibody (mAb) within 4 weeks prior to study Day&#xD;
             1 or has not recovered (i.e. ≤ Grade 1 or at Baseline) from adverse events (AEs) due&#xD;
             to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy&#xD;
             within 14 days prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at&#xD;
             baseline) from AEs due to a previously administered agent.&#xD;
&#xD;
          -  Has received transfusion of blood products (including platelets or red blood cells) or&#xD;
             administration of colony stimulating factors within 4 weeks prior to study Day 1.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis.&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs).&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
          -  Has a history of interstitial lung disease.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the study.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV).&#xD;
&#xD;
          -  Has known active Hepatitis B or Hepatitis C.&#xD;
&#xD;
          -  Has received a live-virus vaccination within 30 days of planned treatment start.&#xD;
&#xD;
          -  Has had an allogenic tissue/solid organ transplant.&#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>Call for Information (Investigational Site 0002)</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Call for Information (Investigational Site 0001)</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Merck Canada</name>
      <address>
        <city>Kirkland</city>
        <state>Quebec</state>
        <zip>H9H 4M7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://merckoncologyclinicaltrials.com</url>
    <description>Merck Oncology Clinical Trials Information</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <last_update_submitted>March 1, 2023</last_update_submitted>
  <last_update_submitted_qc>March 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 2, 2023</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>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</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/NCT02972034
org study id: 8353-013
secondary id: MK-8353-013
secondary id: 2016-003478-42
nct id: NCT02972034
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety, tolerability and preliminary efficacy of MK-8353 when
      administered in combination with pembrolizumab (MK-3475). There are two parts in this study:
      Part 1 will be dose escalation and confirmation, and Part 2 will be a cohort expansion. In
      Part 1, the recommended phase II dose (RP2D) of MK-8353 in combination with a fixed dose of
      pembrolizumab in participants with advanced malignancies will be identified and confirmed.
      Participants will be initially enrolled to receive MK-8353 at 350 mg twice a day (BID) in
      combination with pembrolizumab at a fixed dose of 200 mg on Day 1 of each 3-week cycle (Q3W)
      for up to 24 months of treatment. In Part 2, participants with advanced colorectal cancer
      (CRC) that is microsatellite stable (i.e., non-microsatellite instability-high/deficient
      mismatch repair [non-MSI-H/dMMR]) who received at least one and up to five prior lines of
      therapy will be enrolled at the RP2D in the expansion cohort to further evaluate safety and
      efficacy.

      The protocol has been amended to lower the starting doses of MK-8353 in combination with
      pembrolizumab. In addition, 3 arms have been added: one in which MK-8353 will be administered
      continuously once a day (QD) in combination with pembrolizumab, one optional arm in which
      MK-8353 will be administered 1 week on/1 week off QD in combination with pembrolizumab and
      one optional arm in which participants undergo a MK-8353 QD run-in period prior to starting
      combination therapy with pembrolizumab.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Who Experience an Adverse Event (AE)
time frame: Up to 27 months
measure: Percentage of Participants Who Discontinue Study Drug Due to an AE
time frame: Up to 24 months
measure: Percentage of Participants Who Experience a Dose-limiting Toxicity (DLT)
time frame: During Cycle 1 (Arms A, B & C: Up to 21 days; Arm D: Up to 35 days)
measure: Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as Assessed by the Investigator
time frame: Up to 24 months
arm group label: A: MK-8353 BID Continuous+Pembro
arm group type: Experimental
description: Participants receive MK-8353 orally (PO) two times each day (BID) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab (pembro) 200 mg intravenously (IV) on Day 1 of each 21-day cycle for up to 35 cycles.
arm group label: B: MK-8353 QD Continuous+Pembro
arm group type: Experimental
description: Participants receive MK-8353 PO once each day (QD) on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 35 cycles.
arm group label: C: MK-8353 QD 1 Week On/1 Week Off+Pembro
arm group type: Experimental
description: Optional Arm: Participants receive MK-8353 PO QD on Days 1 to 7, Days 15 to 21 and Days 29 to 35 PLUS pembrolizumab 200 mg IV on Day 1 and Day 22 of each 42-day period (based on 2 cycles of 21 days) for up to 35 cycles.
arm group label: D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro
arm group type: Experimental
description: Optional Arm: Participants undergo an MK-8353 PO QD run-in period from Day -14 to Day -1 prior to Cycle 1 during which they receive MK-8353 PO QD. After the run-in period, participants receive MK-8353 PO QD on Days 1 through 21 of each 21-day cycle PLUS pembrolizumab 200 mg IV on Day 1 of each 21-day cycle for up to 36 cycles.
intervention type: Drug
intervention name: MK-8353
description: PO capsule
arm group label: A: MK-8353 BID Continuous+Pembro
arm group label: B: MK-8353 QD Continuous+Pembro
arm group label: C: MK-8353 QD 1 Week On/1 Week Off+Pembro
arm group label: D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro
intervention type: Biological
intervention name: Pembrolizumab
description: IV infusion
arm group label: A: MK-8353 BID Continuous+Pembro
arm group label: B: MK-8353 QD Continuous+Pembro
arm group label: C: MK-8353 QD 1 Week On/1 Week Off+Pembro
arm group label: D: MK-8353 QD Run-in→MK-8353 QD Continuous+Pembro
other name: MK-3475
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
facility: 
facility: 
facility: 
country: Canada
country: United States
url: http://merckoncologyclinicaltrials.com
description: Merck Oncology Clinical Trials Information
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Pembrolizumab
sharing ipd: Yes
ipd description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php