<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/NCT03790488</url>
  </required_header>
  <id_info>
    <org_study_id>JTX-4014-101</org_study_id>
    <nct_id>NCT03790488</nct_id>
  </id_info>
  <brief_title>Study of a PD-1 Inhibitor (JTX-4014) in Subjects With Solid Tumor Malignancies</brief_title>
  <official_title>Phase 1 First in Human Study of Programmed Cell Death Receptor-1 (PD-1) Inhibitor Monoclonal Antibody (mAb) JTX-4014 in Adult Subjects With Advanced Refractory Solid Tumor Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jounce Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Jounce Therapeutics, Inc.</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>
      JTX-4014-101 is a Phase 1, open label, dose escalation clinical study of JTX-4014 in adult&#xD;
      subjects with advanced refractory solid tumor malignancies, to determine the maximum&#xD;
      tolerated dose (MTD) and recommended Phase 2 dose (RP2D).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      JTX-4014 is a fully human IgG4 monoclonal antibody designed to specifically bind to PD-1 and&#xD;
      block its interaction with its ligands, PD-L1 and PD-L2, to augment anti-tumor T cell&#xD;
      activity. This is a Phase 1, first in human, open label, multicenter, dose escalation&#xD;
      clinical study to evaluate the safety, tolerability, and PK of JTX-4014 when administered as&#xD;
      a single agent to adult subjects with advanced refractory solid tumor malignancies. The&#xD;
      intent of this study will be to determine the MTD and RP2D.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 6, 2018</start_date>
  <completion_date type="Actual">February 28, 2023</completion_date>
  <primary_completion_date type="Actual">July 2, 2019</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>% subjects with adverse events (AEs)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>% subjects with serious adverse events (SAEs)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>% subjects with dose-limiting toxicities (DLTs)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>% subjects with changes from baseline in pro-inflammatory cytokines</measure>
    <time_frame>Approximately 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>% subjects with clinically significant change from baseline in clinical laboratory tests</measure>
    <time_frame>Approximately 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JTX-4014</measure>
    <time_frame>Approximately 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration in serum (Cmax)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to Cmax (Tmax)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration-time curve (AUC)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Last measurable concentration (Clast)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to last measurable concentration (Tlast)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2)</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio of JTX-4014</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate anti-drug antibodies (ADA) against JTX-4014</measure>
    <time_frame>Approximately 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Cancer</condition>
  <arm_group>
    <arm_group_label>JTX-4014</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1 dose escalation of PD-1 inhibitor mAb JTX-4014 by intravenous infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>JTX-4014</intervention_name>
    <description>Specified dose on specified days</description>
    <arm_group_label>JTX-4014</arm_group_label>
    <other_name>PD-1 Inhibitor</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Able and willing to participate and comply with all study requirements and provide&#xD;
             signed and dated informed consent prior to initiation of any study procedures;&#xD;
&#xD;
          2. Histologically or cytologically confirmed extracranial solid tumor malignancy that is&#xD;
             recurrent, metastatic, or persistent after at least 1 line of standard therapy and&#xD;
             with no further standard treatment options that are likely to provide meaningful&#xD;
             clinical benefit;&#xD;
&#xD;
          3. Evaluable or measurable disease, according to the RECIST version 1.1, that has&#xD;
             objectively progressed since (or on) previous treatment as assessed by the&#xD;
             Investigator; while target lesions are not required, target lesions should be measured&#xD;
             if present;&#xD;
&#xD;
          4. ≥ 18 years of age;&#xD;
&#xD;
          5. ECOG performance status 0 or 1;&#xD;
&#xD;
          6. Predicted life expectancy of ≥ 3 months;&#xD;
&#xD;
          7. Have laboratory values (obtained ≤ 28 days prior to first infusion day) in accordance&#xD;
             with the study protocol;&#xD;
&#xD;
          8. For women of childbearing potential (WOCBP): negative serum pregnancy test within 72&#xD;
             hours prior to planned Cycle 1 Day 1 (C1D1) and a negative urine pregnancy test on&#xD;
             C1D1;&#xD;
&#xD;
          9. WOCBP and males whose partners are WOCBP must agree to use a highly effective method&#xD;
             of birth control throughout their participation and for 5 months following the last&#xD;
             study drug administration;&#xD;
&#xD;
         10. Subjects with medical history of the following must be discussed with the Medical&#xD;
             Monitor:&#xD;
&#xD;
               1. Prior biliary tract disorders (as based on hepatobiliary system organ class high&#xD;
                  level terms of: obstructive bile duct disorders, hepatic vascular disorders,&#xD;
                  structural and other bile duct disorders).&#xD;
&#xD;
               2. Portal hypertension and/or hepatic vascular disorders.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Concurrent anticancer treatment, either FDA-approved, palliative, or investigational&#xD;
             for the cancer being evaluated in this study or for other cancers (with&#xD;
             protocol-specified exceptions);&#xD;
&#xD;
          2. Prior receipt of a PD-1 or PD-L1 inhibitor mAb, including JTX-4014;&#xD;
&#xD;
          3. The therapies listed below within the specified timeframe or ongoing toxicity&#xD;
             attributed to prior therapy that was &gt; Grade 1 according to the NCI CTCAE, with&#xD;
             protocol-specified exceptions:&#xD;
&#xD;
               1. Major surgery &lt; 4 weeks prior to planned C1D1;&#xD;
&#xD;
               2. Biologic therapy, including non-PD-1/PD-L1 inhibitor immunotherapy, &lt; 28 days&#xD;
                  prior to planned C1D1;&#xD;
&#xD;
               3. Chemotherapy &lt; 21 days prior to planned C1D1, or &lt; 42 days for mitomycin or&#xD;
                  nitrosoureas;&#xD;
&#xD;
               4. Targeted small molecule therapy &lt; 14 days prior to planned C1D1;&#xD;
&#xD;
               5. Hormonal or other adjunctive therapy for cancers other than the cancer under&#xD;
                  evaluation in this study that started &lt; 14 days prior to planned C1D1, with&#xD;
                  protocol-specified exceptions;&#xD;
&#xD;
               6. Radiation therapy &lt; 21 days prior to planned C1D1, with protocol-specified&#xD;
                  exceptions;&#xD;
&#xD;
               7. Any prior organ transplantation, including allogeneic or autologous stem cell&#xD;
                  transplantation;&#xD;
&#xD;
          4. History of intolerance, hypersensitivity, or treatment discontinuation due to severe&#xD;
             immune-related adverse events on prior non PD 1/PD L1 inhibitor immunotherapy;&#xD;
&#xD;
          5. Diagnosis of immunodeficiency, either primary or acquired, or treatment with&#xD;
             immunosuppressive levels of systemic corticosteroids or any other form of&#xD;
             immunosuppressive therapy within 7 days prior to planned C1D1, with protocol-specified&#xD;
             exceptions;&#xD;
&#xD;
          6. Known severe intolerance or life-threatening hypersensitivity reactions to humanized&#xD;
             mAbs or intravenous immunoglobulin preparations; any history of anaphylaxis; prior&#xD;
             history of human anti-human antibody response; known allergy to any of the study&#xD;
             medications, their analogues, or excipients;&#xD;
&#xD;
          7. Symptomatic or uncontrolled brain metastases, leptomeningeal disease, or spinal cord&#xD;
             compression not definitively treated with surgery or radiation, with&#xD;
             protocol-specified exceptions;&#xD;
&#xD;
          8. Active and clinically relevant bacterial, fungal, or viral infection, including known&#xD;
             hepatitis A, B, C, or human immunodeficiency virus;&#xD;
&#xD;
          9. Receipt of live vaccines within 30 days of planned C1D1;&#xD;
&#xD;
         10. Women who are pregnant or breastfeeding or who plan to become pregnant/breastfeed&#xD;
             while on study; men who plan to father children during the study;&#xD;
&#xD;
         11. History of pneumonitis requiring treatment with corticosteroids, interstitial lung&#xD;
             disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis);&#xD;
&#xD;
         12. Symptomatic ascites or pleural effusion;&#xD;
&#xD;
         13. History of acute diverticulitis, intra-abdominal abscess, gastrointestinal&#xD;
             obstruction, or abdominal carcinomatosis;&#xD;
&#xD;
         14. Symptomatic cardiac or cerebrovascular disease that is unresponsive to surgical or&#xD;
             medical management;&#xD;
&#xD;
         15. Medical or social condition that, in the opinion of the Investigator, might place the&#xD;
             subject at increased risk, adversely affect compliance, or confound safety or other&#xD;
             clinical study data interpretation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Stew Kroll</last_name>
    <role>Study Director</role>
    <affiliation>Jounce Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute at HealthONE</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - Sarasota Cattlemen</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START Midwest - Cancer &amp; Hematology Centers of Western Michigan</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Texas Accelerated Research Therapeutics (START)</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</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>December 21, 2018</study_first_submitted>
  <study_first_submitted_qc>December 28, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 31, 2018</study_first_posted>
  <last_update_submitted>June 28, 2023</last_update_submitted>
  <last_update_submitted_qc>June 28, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid Tumor Malignancies</keyword>
  <keyword>JTX-4014</keyword>
  <keyword>Monoclonal Antibody (mAb)</keyword>
  <keyword>Programmed Cell Death Receptor-1 (PD-1)</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Immuno-oncology</keyword>
  <keyword>Dose Escalation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immune Checkpoint Inhibitors</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03790488
org study id: JTX-4014-101
nct id: NCT03790488
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
JTX-4014-101 is a Phase 1, open label, dose escalation clinical study of JTX-4014 in adult
      subjects with advanced refractory solid tumor malignancies, to determine the maximum
      tolerated dose (MTD) and recommended Phase 2 dose (RP2D).
JTX-4014 is a fully human IgG4 monoclonal antibody designed to specifically bind to PD-1 and
      block its interaction with its ligands, PD-L1 and PD-L2, to augment anti-tumor T cell
      activity. This is a Phase 1, first in human, open label, multicenter, dose escalation
      clinical study to evaluate the safety, tolerability, and PK of JTX-4014 when administered as
      a single agent to adult subjects with advanced refractory solid tumor malignancies. The
      intent of this study will be to determine the MTD and RP2D.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: % subjects with adverse events (AEs)
time frame: Approximately 12 months
measure: % subjects with serious adverse events (SAEs)
time frame: Approximately 12 months
measure: % subjects with dose-limiting toxicities (DLTs)
time frame: Approximately 12 months
measure: % subjects with changes from baseline in pro-inflammatory cytokines
time frame: Approximately 12 months
measure: % subjects with clinically significant change from baseline in clinical laboratory tests
time frame: Approximately 12 months
measure: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of JTX-4014
time frame: Approximately 12 months
measure: Maximum measured concentration in serum (Cmax)
time frame: Approximately 12 months
measure: Time from dosing to Cmax (Tmax)
time frame: Approximately 12 months
measure: Area under the serum concentration-time curve (AUC)
time frame: Approximately 12 months
measure: Last measurable concentration (Clast)
time frame: Approximately 12 months
measure: Time to last measurable concentration (Tlast)
time frame: Approximately 12 months
measure: Terminal half-life (t1/2)
time frame: Approximately 12 months
measure: Accumulation ratio of JTX-4014
time frame: Approximately 12 months
measure: Evaluate anti-drug antibodies (ADA) against JTX-4014
time frame: Approximately 12 months
arm group label: JTX-4014
arm group type: Experimental
description: Phase 1 dose escalation of PD-1 inhibitor mAb JTX-4014 by intravenous infusion
intervention type: Drug
intervention name: JTX-4014
description: Specified dose on specified days
arm group label: JTX-4014
other name: PD-1 Inhibitor
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Stew Kroll
role: Study Director
affiliation: Jounce Therapeutics, Inc.
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Immune Checkpoint Inhibitors
sharing ipd: No