<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/NCT03254927</url>
  </required_header>
  <id_info>
    <org_study_id>CDX3379-04</org_study_id>
    <nct_id>NCT03254927</nct_id>
  </id_info>
  <brief_title>A Study of CDX-3379 and Cetuximab and in Patients With Advanced Head and Neck Squamous Cell Carcinoma</brief_title>
  <official_title>A Phase 2, Multicenter, Open-label Study to Evaluate the Efficacy and Safety of CDX-3379 in Combination With Cetuximab in Patients With Advanced Head and Neck Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celldex Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celldex Therapeutics</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 is a study to determine the clinical benefit (how well the drug works), safety and&#xD;
      tolerability of combining CDX-3379 and cetuximab. The study will enroll patients with&#xD;
      advanced head and neck squamous cell carcinoma who have previously received cetuximab and&#xD;
      progressed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      CDX-3379 is a fully human monoclonal antibody that binds to a molecule called human epidermal&#xD;
      growth factor receptor 3 (HER3 or ErbB3) found on certain cells and may act to promote&#xD;
      anti-tumor effects.&#xD;
&#xD;
      Cetuximab is a human monoclonal antibody that blocks EGFR, a protein receptor that regulates&#xD;
      cell growth.&#xD;
&#xD;
      This study will evaluate the safety, tolerability and efficacy of CDX-3379 in combination&#xD;
      with cetuximab in patients with advanced head and neck squamous cell carcinoma who have&#xD;
      previously received cetuximab and progressed.&#xD;
&#xD;
      Eligible patients that enroll in the study will be given the dose of 12 mg/kg CDX-3379 once&#xD;
      every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly&#xD;
      doses of 250 mg/m2 cetuximab.&#xD;
&#xD;
      Up to 45 patients will be enrolled. All patients enrolled in the study will be closely&#xD;
      monitored to determine if there is a response to the treatment as well as for any side&#xD;
      effects that may occur.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision based on emerging risk-benefit profile&#xD;
  </why_stopped>
  <start_date type="Actual">March 27, 2018</start_date>
  <completion_date type="Actual">December 16, 2020</completion_date>
  <primary_completion_date type="Actual">September 16, 2020</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months.</time_frame>
    <description>The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), &gt;= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Response (CBR)</measure>
    <time_frame>Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years</time_frame>
    <description>The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)</time_frame>
    <description>The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS)</measure>
    <time_frame>From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)</time_frame>
    <description>The time from start of study drug to time of progression or death, whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>The time from start of study drug to death from any cause (up to approximately 2 years)</time_frame>
    <description>The time from start of study drug to death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Adverse Events [Safety and Tolerability]</measure>
    <time_frame>Following at least one dose of study treatment through 30 days after last dose of CDX-3379.</time_frame>
    <description>Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor DNA Biomarkers.</measure>
    <time_frame>Tumor tissue is obtained during screening window via single biopsy procedure.</time_frame>
    <description>Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Advanced Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>CDX-3379 and cetuximab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CDX-3379 and cetuximab</intervention_name>
    <description>Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
    <arm_group_label>CDX-3379 and cetuximab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed head and neck squamous cell carcinoma.&#xD;
&#xD;
          2. Human papilloma virus (HPV) negative tumor.&#xD;
&#xD;
          3. Prior treatment with a check-point inhibitor targeting PD-1, unless not a candidate.&#xD;
&#xD;
          4. Prior treatment with cetuximab with tumor progression during or within 6 months after&#xD;
             completing treatment.&#xD;
&#xD;
          5. Measurable disease.&#xD;
&#xD;
          6. Life expectancy ≥ 12 weeks.&#xD;
&#xD;
          7. If of childbearing potential (male or female), agrees to practice an effective form of&#xD;
             contraception during study treatment and for at least 6 months following last&#xD;
             treatment.&#xD;
&#xD;
          8. Willingness to undergo a tumor biopsy prior to starting treatment (or if biopsy is not&#xD;
             feasible, provide archival tissue).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous treatment with CDX-3379 or other anti-ErbB3 targeted agents.&#xD;
&#xD;
          2. Nasal, paranasal sinus, or nasopharyngeal carcinoma, aside from WHO Type I and II&#xD;
             (keratinizing, non-EBV positive) nasopharyngeal carcinoma which will be allowed.&#xD;
&#xD;
          3. Major surgery within 4 weeks prior to first dose of study treatment.&#xD;
&#xD;
          4. Chemotherapy within 21 days or at least 5 half-lives (whichever is shorter) prior to&#xD;
             first dose of study treatment.&#xD;
&#xD;
          5. Monoclonal based therapies within 4 weeks (excluding cetuximab) and all other&#xD;
             immunotherapy within 2 weeks prior to first dose of study treatment.&#xD;
&#xD;
          6. Other prior malignancy, active within 3 years, except for localized prostate cancer,&#xD;
             cervical carcinoma in situ, non-melanomatous carcinoma of the skin, stage 1&#xD;
             differentiated thyroid cancer or ductal carcinoma in situ of the breast.&#xD;
&#xD;
          7. Active, untreated central nervous system metastases.&#xD;
&#xD;
          8. Active autoimmune disease or documented history of autoimmune disease.&#xD;
&#xD;
          9. Significant cardiovascular disease including CHF or poorly controlled hypertension.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The University of Arizona Cancer Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale Cancer Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University Medical center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Hospital, Abramson Cancer Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 21, 2017</study_first_posted>
  <results_first_submitted>October 6, 2021</results_first_submitted>
  <results_first_submitted_qc>March 7, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 3, 2023</results_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Erbitux</keyword>
  <keyword>Cetuximab</keyword>
  <keyword>Oral Cancer</keyword>
  <keyword>Oropharyngeal cancer</keyword>
  <keyword>Laryngeal cancer</keyword>
  <keyword>Head and Neck Squamous Cell Carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cetuximab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 28, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03254927/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/27/NCT03254927/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CDX-3379 and Cetuximab</title>
          <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CDX-3379 and Cetuximab</title>
          <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" lower_limit="46" upper_limit="79"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </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="1"/>
                  </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="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Site of Primary Tumor</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Pharynx/Oropharynx</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Oral Cavity</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Larynx</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of Metastatic Disease</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.2" lower_limit="1" upper_limit="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>ECOG Performance Status</title>
          <description>ECOG Performance Status as published in Am. J. Clin. Oncol (Oken, et al. 1982) 0 = Fully active, able to carry on all pre-disease performance without restriction.&#xD;
1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>ECOG 0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>ECOG 1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Objective Response Rate</title>
        <description>The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), &gt;= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.</description>
        <time_frame>The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CDX-3379 and Cetuximab</title>
            <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
          </group>
        </group_list>
        <measure>
          <title>Objective Response Rate</title>
          <description>The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), &gt;= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="0.8" upper_limit="22.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Response (CBR)</title>
        <description>The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks</description>
        <time_frame>Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CDX-3379 and Cetuximab</title>
            <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Response (CBR)</title>
          <description>The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40" lower_limit="22.7" upper_limit="59.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented</description>
        <time_frame>First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CDX-3379 and Cetuximab</title>
            <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented</description>
          <units>months</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA">30 patients were treated, 2 patients achieved objective response. The duration of response was 5 months and 18.7 months for the 2 patients who achieved objective response.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS)</title>
        <description>The time from start of study drug to time of progression or death, whichever occurs first</description>
        <time_frame>From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CDX-3379 and Cetuximab</title>
            <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS)</title>
          <description>The time from start of study drug to time of progression or death, whichever occurs first</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" lower_limit="1.3" upper_limit="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS)</title>
        <description>The time from start of study drug to death</description>
        <time_frame>The time from start of study drug to death from any cause (up to approximately 2 years)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CDX-3379 and Cetuximab</title>
            <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>The time from start of study drug to death</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.6" lower_limit="2.7" upper_limit="7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Adverse Events [Safety and Tolerability]</title>
        <description>Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events.</description>
        <time_frame>Following at least one dose of study treatment through 30 days after last dose of CDX-3379.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>CDX-3379 and Cetuximab</title>
            <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Adverse Events [Safety and Tolerability]</title>
          <description>Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumor DNA Biomarkers.</title>
        <description>Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported.</description>
        <time_frame>Tumor tissue is obtained during screening window via single biopsy procedure.</time_frame>
        <population>patients with FAT1 positive tumors</population>
        <group_list>
          <group group_id="O1">
            <title>CDX-3379 and Cetuximab</title>
            <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor DNA Biomarkers.</title>
          <description>Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported.</description>
          <population>patients with FAT1 positive tumors</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from initiation of treatment until 30 days after discontinuing treatment or initiation of new anti-cancer medication.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CDX-3379 and Cetuximab</title>
          <description>During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.&#xD;
CDX-3379 and cetuximab: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (23.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="26" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Small intestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Mucosal inflammation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lung abscess</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Gastrostomy tube site complication</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Tracheal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Failure to thrive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (23.1)</default_vocab>
        <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="30" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blepharitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Thirst</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Face oedema</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Paronychia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fungal skin infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Radiation skin injury</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood lactate dehydrogenase increased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Malnutrition</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumour pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Proteinuria</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Skin induration</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Pruritis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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>
    <limitations_and_caveats>Study was terminated early due to unfavorable risk/benefit profile.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Celldex Therapeutics</organization>
      <phone>844-723-9363</phone>
      <email>info@celldex.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03254927
org study id: CDX3379-04
nct id: NCT03254927
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a study to determine the clinical benefit (how well the drug works), safety and
      tolerability of combining CDX-3379 and cetuximab. The study will enroll patients with
      advanced head and neck squamous cell carcinoma who have previously received cetuximab and
      progressed.
CDX-3379 is a fully human monoclonal antibody that binds to a molecule called human epidermal
      growth factor receptor 3 (HER3 or ErbB3) found on certain cells and may act to promote
      anti-tumor effects.

      Cetuximab is a human monoclonal antibody that blocks EGFR, a protein receptor that regulates
      cell growth.

      This study will evaluate the safety, tolerability and efficacy of CDX-3379 in combination
      with cetuximab in patients with advanced head and neck squamous cell carcinoma who have
      previously received cetuximab and progressed.

      Eligible patients that enroll in the study will be given the dose of 12 mg/kg CDX-3379 once
      every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly
      doses of 250 mg/m2 cetuximab.

      Up to 45 patients will be enrolled. All patients enrolled in the study will be closely
      monitored to determine if there is a response to the treatment as well as for any side
      effects that may occur.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate
time frame: The proportion of evaluable patients who achieve a best overall response of complete or partial response according to RECIST 1.1 assessed up to 24 months.
description: The percentage of patients who achieve a complete response or partial response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST version 1.1), Complete Response (CR) = disappearance of all target lesions and non-target lesions, Partial Response (PR), >= 30% decrease in the sum of the longest diameter of target lesions with no progression in non-target lesions and no new lesions.
measure: Clinical Benefit Response (CBR)
time frame: Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 2 years
description: The percentage of patients who achieve best response of confirmed CR or PR, or stable disease (SD) for at least 12 weeks
measure: Duration of Response (DOR)
time frame: First occurrence of a documented objective response to disease progression or death (up to approximately 2 years)
description: The interval from which measurement criteria are first met for Complete Response (CR) or Partial Response (PR) until the first date that progressive disease is objectively documented
measure: Progression-free Survival (PFS)
time frame: From first dose to the first occurrence of disease progression or death due to any cause (up to approximately 2 years)
description: The time from start of study drug to time of progression or death, whichever occurs first
measure: Overall Survival (OS)
time frame: The time from start of study drug to death from any cause (up to approximately 2 years)
description: The time from start of study drug to death
measure: Incidence of Adverse Events [Safety and Tolerability]
time frame: Following at least one dose of study treatment through 30 days after last dose of CDX-3379.
description: Safety and tolerability of CDX-3379 in combination with cetuximab as determined by incidence and severity of adverse events. Percentage of patients reporting one or more adverse events.
measure: Tumor DNA Biomarkers.
time frame: Tumor tissue is obtained during screening window via single biopsy procedure.
description: Tumor DNA biomarkers will be evaluated and assessed for correlation with clinical efficacy. Objective response rate for subset of patients with FAT1 positive tumor is reported.
arm group label: CDX-3379 and cetuximab
arm group type: Experimental
description: During the treatment phase of the study, eligible patients will receive assigned treatments in 3 week cycles until progression.
intervention type: Drug
intervention name: CDX-3379 and cetuximab
description: Dose: 12 mg/kg CDX-3379 once every 3 weeks in combination with 400 mg/m2 cetuximab on the first day followed by weekly doses of 250 mg/m2 cetuximab.
arm group label: CDX-3379 and cetuximab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Cetuximab
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was terminated early due to unfavorable risk/benefit profile.
point of contact: 