<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/NCT04440943</url>
  </required_header>
  <id_info>
    <org_study_id>CDX527-01</org_study_id>
    <nct_id>NCT04440943</nct_id>
  </id_info>
  <brief_title>A Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies</brief_title>
  <official_title>A Phase 1 Study of the PD-L1xCD27 Bispecific Antibody CDX-527 in Patients With Advanced Malignancies</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>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, non-randomized, multicenter, dose-escalation and expansion study in&#xD;
      patients with selected solid tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will determine the safety, tolerability and activity of CDX-527.&#xD;
&#xD;
      Eligible patients that enroll to the dose-escalation portion of the study will be assigned to&#xD;
      one of several dose levels of CDX-527. The dose-escalation part of the study will determine&#xD;
      the safety profile of CDX-527 and determine which dose(s) of CDX-527 will be studied in the&#xD;
      expansion part of the study.&#xD;
&#xD;
      The expansion part of the study will enroll eligible patients with certain solid tumors to be&#xD;
      treated at dose(s) identified during dose-escalation&#xD;
&#xD;
      Up to 40 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>Completed</overall_status>
  <start_date type="Actual">August 4, 2020</start_date>
  <completion_date type="Actual">April 6, 2023</completion_date>
  <primary_completion_date type="Actual">April 6, 2023</primary_completion_date>
  <phase>Phase 1</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>Safety and Tolerability of CDX-527 as assessed by CTCAE v5.0</measure>
    <time_frame>From first dose through 28 days after last dose</time_frame>
    <description>The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate</measure>
    <time_frame>Every 8 weeks starting with first dose until disease progression, assessed up to approximately 1-2 years.</time_frame>
    <description>The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate</measure>
    <time_frame>Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 1-2 years.</time_frame>
    <description>The percentage of patients who achieve best response of confirmed iCR or iPR, or immune stable disease (iSD) for at least four months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>First occurrence of a documented objective response to disease progression or death (up to approximately 1-2 years)</time_frame>
    <description>The interval from which measurement criteria are first met for iCR or iPR until the first date that progressive disease is objectively documented</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>From the first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-2 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</measure>
    <time_frame>The time from start of study drug to death from any cause (up to approximately 1-2 years)</time_frame>
    <description>The time from start of study drug to death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity Evaluation</measure>
    <time_frame>Prior to the first dose of study treatment, then intermittently before dosing, and up to 60 days after the last dose</time_frame>
    <description>Serum samples will be obtained for assessment of human anti-CDX-527 antibodies</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic Evaluation</measure>
    <time_frame>Before and after dosing, with additional timepoints after the first two doses, then intermittently before dosing and up to 60 days after the last dose</time_frame>
    <description>CDX-527 serum concentrations will be measured at specified visits.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <condition>Breast Cancer</condition>
  <condition>Gastric Cancer</condition>
  <condition>Renal Cell Carcinoma</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Primary Peritoneal Carcinoma</condition>
  <condition>Fallopian Tube Cancer</condition>
  <condition>Cholangiocarcinoma</condition>
  <condition>Bladder Urothelial Carcinoma</condition>
  <condition>MSI-H Colorectal Cancer</condition>
  <condition>Esophageal Cancer</condition>
  <condition>Hepatic Cancer</condition>
  <condition>Head and Neck Cancer</condition>
  <condition>Other Solid Tumors</condition>
  <arm_group>
    <arm_group_label>CDX-527</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose-escalation phase: Eligible patients will receive CDX-527 treatment based on cohort assigned until progression or intolerance.&#xD;
Expansion phase: Patients will receive CDX-527 at the dose level(s) chosen during the escalation phase.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CDX-527</intervention_name>
    <description>CDX-527 is administered by infusion every 2 weeks</description>
    <arm_group_label>CDX-527</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Recurrent, locally advanced or metastatic solid tumor cancer excluding the following:&#xD;
             MSI-low colorectal cancer, glioblastoma multiforme, prostate cancer, pancreatic&#xD;
             cancer, mucosal and ocular melanoma.&#xD;
&#xD;
          2. Receipt of all standard therapies for the tumor type&#xD;
&#xD;
          3. Measurable (target) disease by iRECIST&#xD;
&#xD;
          4. If of childbearing potential (male or female), agrees to practice an effective form of&#xD;
             contraception during study treatment and for at least 3 months following last&#xD;
             treatment&#xD;
&#xD;
          5. Willingness to undergo a pre-treatment and on-treatment biopsy, if required&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. History of severe hypersensitivity reactions to other monoclonal antibodies.&#xD;
&#xD;
          2. Previous treatment with any anti-CD27 antibody.&#xD;
&#xD;
          3. Inadequate washout period from prior therapy as defined in the Protocol.&#xD;
&#xD;
          4. Patients who have received more than 0 or 1 prior PD-1/PD-L1 inhibitor depending on&#xD;
             their tumor type&#xD;
&#xD;
          5. Major surgery within 4 weeks prior to study treatment.&#xD;
&#xD;
          6. Use of immunosuppressive medications within 4 weeks or systemic corticosteroids within&#xD;
             2 weeks prior to study treatment.&#xD;
&#xD;
          7. Other prior malignancy, except for adequately treated basal or squamous cell skin&#xD;
             cancer or in situ cancers. For all other cancers, the patient must be disease-free for&#xD;
             at least 3 years to be allowed to enroll.&#xD;
&#xD;
          8. Thrombotic events within the last 6 months prior to study treatment&#xD;
&#xD;
          9. Active, untreated central nervous system metastases.&#xD;
&#xD;
         10. Active autoimmune disease or documented history of autoimmune disease.&#xD;
&#xD;
         11. History of (non-infectious) pneumonitis or has current pneumonitis.&#xD;
&#xD;
         12. Active diverticulitis&#xD;
&#xD;
         13. Known infection of HIV, Hepatitis B, or Hepatitis C.&#xD;
&#xD;
        There are additional criteria your study doctor will review with you to confirm your&#xD;
        eligibility for the study.&#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>Northside Hospital</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oncology Hematology West, PC dba Nebraska Cancer Specialists</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke Cancer Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <last_update_submitted>June 16, 2023</last_update_submitted>
  <last_update_submitted_qc>June 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Fallopian Tube Neoplasms</mesh_term>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04440943
org study id: CDX527-01
nct id: NCT04440943
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is an open-label, non-randomized, multicenter, dose-escalation and expansion study in
      patients with selected solid tumors.
This study will determine the safety, tolerability and activity of CDX-527.

      Eligible patients that enroll to the dose-escalation portion of the study will be assigned to
      one of several dose levels of CDX-527. The dose-escalation part of the study will determine
      the safety profile of CDX-527 and determine which dose(s) of CDX-527 will be studied in the
      expansion part of the study.

      The expansion part of the study will enroll eligible patients with certain solid tumors to be
      treated at dose(s) identified during dose-escalation

      Up to 40 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: Safety and Tolerability of CDX-527 as assessed by CTCAE v5.0
time frame: From first dose through 28 days after last dose
description: The rates of drug-related adverse events will be summarized and maximum tolerated dose will be determined.
measure: Objective Response Rate
time frame: Every 8 weeks starting with first dose until disease progression, assessed up to approximately 1-2 years.
description: The percentage of patients who achieve a confirmed immune complete response (iCR) or immune partial response (iPR)
measure: Clinical Benefit Rate
time frame: Every 8 weeks, starting with first dose until disease progression, assessed up to approximately 1-2 years.
description: The percentage of patients who achieve best response of confirmed iCR or iPR, or immune stable disease (iSD) for at least four months
measure: Duration of Response
time frame: First occurrence of a documented objective response to disease progression or death (up to approximately 1-2 years)
description: The interval from which measurement criteria are first met for iCR or iPR until the first date that progressive disease is objectively documented
measure: Progression-free Survival
time frame: From the first dose to the first occurrence of disease progression or death due to any cause (up to approximately 1-2 years)
description: The time from start of study drug to time of progression or death, whichever occurs first
measure: Overall Survival
time frame: The time from start of study drug to death from any cause (up to approximately 1-2 years)
description: The time from start of study drug to death
measure: Immunogenicity Evaluation
time frame: Prior to the first dose of study treatment, then intermittently before dosing, and up to 60 days after the last dose
description: Serum samples will be obtained for assessment of human anti-CDX-527 antibodies
measure: Pharmacokinetic Evaluation
time frame: Before and after dosing, with additional timepoints after the first two doses, then intermittently before dosing and up to 60 days after the last dose
description: CDX-527 serum concentrations will be measured at specified visits.
arm group label: CDX-527
arm group type: Experimental
description: Dose-escalation phase: Eligible patients will receive CDX-527 treatment based on cohort assigned until progression or intolerance.
Expansion phase: Patients will receive CDX-527 at the dose level(s) chosen during the escalation phase.
intervention type: Drug
intervention name: CDX-527
description: CDX-527 is administered by infusion every 2 weeks
arm group label: CDX-527
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Cholangiocarcinoma
mesh term: Fallopian Tube Neoplasms
mesh term: Liver Neoplasms