<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/NCT03241927</url>
  </required_header>
  <id_info>
    <org_study_id>GCO 16-2526</org_study_id>
    <nct_id>NCT03241927</nct_id>
  </id_info>
  <brief_title>Pembrolizumab Effects on NK Cell Exhaustion in Melanoma (Merck NK-IIT)</brief_title>
  <official_title>A Phase II Study Assessing the Effect of Pembrolizumab Induced Changes to the NK Cell Exhaustion Phenotype on the Efficacy of PD-1 Targeted Treatment in Patients With Unresectable Stage III or Stage IV Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nina Bhardwaj</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Icahn School of Medicine at Mount Sinai</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>
      Melanoma is an immune-modulated malignancy and immune checkpoint modulators which inhibit&#xD;
      PD-1 function (pembrolizumab, nivolumab) have demonstrated clinical efficacy as treatment for&#xD;
      patients with stage IV melanoma. Pembrolizumab across a range of doses in phase I&#xD;
      investigation has demonstrated clinical efficacy with RR approximately 27%. By better&#xD;
      understanding how NK cell function and exhaustion interplays with PD1 function and activity,&#xD;
      potentially more efficacious combination therapies can be developed. The pharmacodynamic&#xD;
      studies to be performed as part of this trial will provide such information.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    difficult enrollment&#xD;
  </why_stopped>
  <start_date type="Actual">December 20, 2017</start_date>
  <completion_date type="Actual">June 6, 2018</completion_date>
  <primary_completion_date type="Actual">June 6, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent of LAMP-1 Positive Cells</measure>
    <time_frame>up to 3 years</time_frame>
    <description>NK cell exhaustion will be assess by flow cytometry and expressed as % of LAMP-1 positive cells.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of Positive Cell for IFN Gamma</measure>
    <time_frame>up to 3 years</time_frame>
    <description>IFN gamma will be assess by flow cytometry and then expressed as % of positive cell for IFN gamma.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of Proliferating Cells</measure>
    <time_frame>up to 3 years</time_frame>
    <description>NK proliferation will be assess by flow cytometry and then expressed as percentage of proliferating cells.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MICA Plasma Level</measure>
    <time_frame>up to 104 levels</time_frame>
    <description>MICA plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HMGB-1 Plasma Level</measure>
    <time_frame>up to 104 weeks</time_frame>
    <description>HMGB-1 plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>% of Positive NK Cells for CEACAM-1</measure>
    <time_frame>up to 104 weeks</time_frame>
    <description>CEACAM-1 expression will be assessed by flow cytometry and express as % of positive NK cells for CEACAM-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Overall Survival</measure>
    <time_frame>1 year</time_frame>
    <description>One year survival following pembrolizumab treatment in patients with Unresectable stage III or IV melanoma using Immune-Related Response Criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) Rate</measure>
    <time_frame>6 months</time_frame>
    <description>Progression free survival in pembrolizumab treated patients with unresectable stage III or IV melanoma using Immune-Related Response Criteria.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg IV infusion every 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Donors</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Day 1 of each 3 week cycle</description>
    <arm_group_label>Pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be willing and able to provide written informed consent/assent for the trial.&#xD;
&#xD;
          -  Have Unresectable stage III or stage IV melanoma&#xD;
&#xD;
          -  Be ≥ 18 years of age on day of signing informed consent.&#xD;
&#xD;
          -  Have measurable disease based on RECIST 1.1 and be able to be followed over time by&#xD;
             Immune related response criteria (irRC) for treatment decisions.&#xD;
&#xD;
          -  Have a performance status of 0, 1, or 2 on the ECOG Performance Scale.&#xD;
&#xD;
          -  Demonstrate adequate organ function as defined in Table 1, all screening labs should&#xD;
             be performed within 10 days of treatment initiation.&#xD;
&#xD;
          -  Female subjects of childbearing potential should have a negative urine or serum&#xD;
             pregnancy within 72 hours prior to receiving the first dose of study medication. If&#xD;
             the urine test is positive or cannot be confirmed as negative, a serum pregnancy test&#xD;
             will be required.&#xD;
&#xD;
          -  Female subjects of childbearing potential should be willing to use 2 methods of birth&#xD;
             control or be surgically sterile, or abstain from heterosexual activity for the course&#xD;
             of the study through 120 days after the last dose of study medication (Reference&#xD;
             Section 5.6.2). Subjects of childbearing potential are those who have not been&#xD;
             surgically sterilized or have not been free from menses for &gt; 1 year.&#xD;
&#xD;
          -  Male subjects should agree to use an adequate method of contraception starting with&#xD;
             the first dose of study therapy through 120 days after the last dose of study therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is currently participating and receiving study therapy or has participated in a study&#xD;
             of an investigational agent and received study therapy or used an investigational&#xD;
             device within 4 weeks prior to the first dose of treatment.&#xD;
&#xD;
          -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of systemic immunosuppressive therapy within 7 days prior to the first dose&#xD;
             of trial treatment. Topical, inhaled, ocular, and intra-articular steroids are not&#xD;
             exclusionary.&#xD;
&#xD;
          -  Has a known history of active TB (Bacillus Tuberculosis).&#xD;
&#xD;
          -  Hypersensitivity to pembrolizumab or any of its excipients.&#xD;
&#xD;
          -  Has had a prior anti-cancer monoclonal antibody (mAb) treatment within 4 weeks prior&#xD;
             to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse&#xD;
             events due to agents administered more than 4 weeks earlier.&#xD;
&#xD;
          -  Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy&#xD;
             within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at&#xD;
             baseline) from adverse events due to a previously administered agent. - Note: Subjects&#xD;
             with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the&#xD;
             study.&#xD;
&#xD;
          -  Note: If subject received major surgery, the subject must have recovered adequately&#xD;
             from the toxicity and/or complications from the intervention prior to starting&#xD;
             therapy.&#xD;
&#xD;
          -  Has a known additional malignancy that is progressing or requires active treatment.&#xD;
             Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the&#xD;
             skin that has undergone potentially curative therapy or in situ cervical cancer&#xD;
&#xD;
          -  Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Subjects with previously treated brain metastases may participate provided&#xD;
             the subjects are stable (without evidence of progression by imaging for at least four&#xD;
             weeks prior to the first dose of trial treatment and any neurologic symptoms have&#xD;
             returned to baseline), have no evidence of new or enlarging brain metastases, and are&#xD;
             not using steroids for at least 7 days prior to trial treatment. This exception does&#xD;
             not include carcinomatous meningitis, which is excluded regardless of clinical&#xD;
             stability.&#xD;
&#xD;
          -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (eg. thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis.&#xD;
&#xD;
          -  Has an active infection requiring systemic therapy.&#xD;
&#xD;
          -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
          -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
             cooperation with the requirements of the trial.&#xD;
&#xD;
          -  If pregnant or breastfeeding, or expecting to conceive or father children within the&#xD;
             projected duration of the trial, starting with the pre-screening or screening visit&#xD;
             through 120 days after the last dose of trial treatment.&#xD;
&#xD;
          -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
          -  Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).&#xD;
&#xD;
          -  Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA&#xD;
             [qualitative] is detected).&#xD;
&#xD;
          -  Has received a live vaccine within 30 days of planned start of study therapy.&#xD;
&#xD;
          -  Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines&#xD;
             and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live&#xD;
             attenuated vaccines and are not allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nina Bhardwaj, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Icahn School of Medicine at Mount Sinai</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>August 2, 2017</study_first_submitted>
  <study_first_submitted_qc>August 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 8, 2017</study_first_posted>
  <results_first_submitted>October 29, 2020</results_first_submitted>
  <results_first_submitted_qc>October 29, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 23, 2020</results_first_posted>
  <last_update_submitted>October 29, 2020</last_update_submitted>
  <last_update_submitted_qc>October 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Icahn School of Medicine at Mount Sinai</investigator_affiliation>
    <investigator_full_name>Nina Bhardwaj</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Pembrolizumab</keyword>
  <keyword>NK Cell Exhaustion</keyword>
  <keyword>PD-1</keyword>
  <keyword>Unresectable</keyword>
  <keyword>Stage III</keyword>
  <keyword>Stage IV</keyword>
  <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>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 23, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03241927/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>4 Participants consented, 1 with unstable CNS and not eligible, 2 withdrew consent. and 1 enrolled.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Pembrolizumab</title>
          <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
        </group>
        <group group_id="P2">
          <title>Healthy Donors</title>
          <description>Healthy participants</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </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="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>study terminated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </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>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>60-69 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>80-89 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent of LAMP-1 Positive Cells</title>
        <description>NK cell exhaustion will be assess by flow cytometry and expressed as % of LAMP-1 positive cells.</description>
        <time_frame>up to 3 years</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of LAMP-1 Positive Cells</title>
          <description>NK cell exhaustion will be assess by flow cytometry and expressed as % of LAMP-1 positive cells.</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percent of Positive Cell for IFN Gamma</title>
        <description>IFN gamma will be assess by flow cytometry and then expressed as % of positive cell for IFN gamma.</description>
        <time_frame>up to 3 years</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Positive Cell for IFN Gamma</title>
          <description>IFN gamma will be assess by flow cytometry and then expressed as % of positive cell for IFN gamma.</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percent of Proliferating Cells</title>
        <description>NK proliferation will be assess by flow cytometry and then expressed as percentage of proliferating cells.</description>
        <time_frame>up to 3 years</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Proliferating Cells</title>
          <description>NK proliferation will be assess by flow cytometry and then expressed as percentage of proliferating cells.</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>MICA Plasma Level</title>
        <description>MICA plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.</description>
        <time_frame>up to 104 levels</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>MICA Plasma Level</title>
          <description>MICA plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>HMGB-1 Plasma Level</title>
        <description>HMGB-1 plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.</description>
        <time_frame>up to 104 weeks</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>HMGB-1 Plasma Level</title>
          <description>HMGB-1 plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>% of Positive NK Cells for CEACAM-1</title>
        <description>CEACAM-1 expression will be assessed by flow cytometry and express as % of positive NK cells for CEACAM-1</description>
        <time_frame>up to 104 weeks</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>% of Positive NK Cells for CEACAM-1</title>
          <description>CEACAM-1 expression will be assessed by flow cytometry and express as % of positive NK cells for CEACAM-1</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Overall Survival</title>
        <description>One year survival following pembrolizumab treatment in patients with Unresectable stage III or IV melanoma using Immune-Related Response Criteria.</description>
        <time_frame>1 year</time_frame>
        <population>Data not collected</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Overall Survival</title>
          <description>One year survival following pembrolizumab treatment in patients with Unresectable stage III or IV melanoma using Immune-Related Response Criteria.</description>
          <population>Data not collected</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival (PFS) Rate</title>
        <description>Progression free survival in pembrolizumab treated patients with unresectable stage III or IV melanoma using Immune-Related Response Criteria.</description>
        <time_frame>6 months</time_frame>
        <population>only one subject in study</population>
        <group_list>
          <group group_id="O1">
            <title>Pembrolizumab</title>
            <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
          </group>
          <group group_id="O2">
            <title>Healthy Donors</title>
            <description>Healthy participants</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival (PFS) Rate</title>
          <description>Progression free survival in pembrolizumab treated patients with unresectable stage III or IV melanoma using Immune-Related Response Criteria.</description>
          <population>only one subject in study</population>
          <units>weeks</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>18 weeks</time_frame>
      <desc>there was only one person in this study. No participants in Healthy Control arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>Pembrolizumab</title>
          <description>200 mg IV infusion every 3 weeks&#xD;
Pembrolizumab: Day 1 of each 3 week cycle</description>
        </group>
        <group group_id="E2">
          <title>Healthy Control</title>
          <description>Healthy Participants</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Bilateral Leg Edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperuricemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hair thinning</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Nina Bhardwaj</name_or_title>
      <organization>Icahn School of Medicine at Mount Sinai</organization>
      <phone>212-824-8427</phone>
      <email>nina.bhardwaj@mssm.edu</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/NCT03241927
org study id: GCO 16-2526
nct id: NCT03241927
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Melanoma is an immune-modulated malignancy and immune checkpoint modulators which inhibit
      PD-1 function (pembrolizumab, nivolumab) have demonstrated clinical efficacy as treatment for
      patients with stage IV melanoma. Pembrolizumab across a range of doses in phase I
      investigation has demonstrated clinical efficacy with RR approximately 27%. By better
      understanding how NK cell function and exhaustion interplays with PD1 function and activity,
      potentially more efficacious combination therapies can be developed. The pharmacodynamic
      studies to be performed as part of this trial will provide such information.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent of LAMP-1 Positive Cells
time frame: up to 3 years
description: NK cell exhaustion will be assess by flow cytometry and expressed as % of LAMP-1 positive cells.
measure: Percent of Positive Cell for IFN Gamma
time frame: up to 3 years
description: IFN gamma will be assess by flow cytometry and then expressed as % of positive cell for IFN gamma.
measure: Percent of Proliferating Cells
time frame: up to 3 years
description: NK proliferation will be assess by flow cytometry and then expressed as percentage of proliferating cells.
measure: MICA Plasma Level
time frame: up to 104 levels
description: MICA plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.
measure: HMGB-1 Plasma Level
time frame: up to 104 weeks
description: HMGB-1 plasma biomarker level associated with reversal of NK cell exhaustion will be assessed by ELISA.
measure: % of Positive NK Cells for CEACAM-1
time frame: up to 104 weeks
description: CEACAM-1 expression will be assessed by flow cytometry and express as % of positive NK cells for CEACAM-1
measure: Incidence of Overall Survival
time frame: 1 year
description: One year survival following pembrolizumab treatment in patients with Unresectable stage III or IV melanoma using Immune-Related Response Criteria.
measure: Progression Free Survival (PFS) Rate
time frame: 6 months
description: Progression free survival in pembrolizumab treated patients with unresectable stage III or IV melanoma using Immune-Related Response Criteria.
arm group label: Pembrolizumab
arm group type: Experimental
description: 200 mg IV infusion every 3 weeks
arm group label: Healthy Donors
arm group type: No Intervention
intervention type: Biological
intervention name: Pembrolizumab
description: Day 1 of each 3 week cycle
arm group label: Pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Nina Bhardwaj, MD, PhD
role: Principal Investigator
affiliation: Icahn School of Medicine at Mount Sinai
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Icahn School of Medicine at Mount Sinai
investigator full name: Nina Bhardwaj
investigator title: Professor
mesh term: Melanoma
mesh term: Pembrolizumab
sharing ipd: Undecided
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 