<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/NCT03835949</url>
  </required_header>
  <id_info>
    <org_study_id>4309ST101</org_study_id>
    <nct_id>NCT03835949</nct_id>
  </id_info>
  <brief_title>Study of TJ004309 in Combination With Atezolizumab (Tecentriq®) in Patients With Advanced or Metastatic Cancer</brief_title>
  <official_title>A Phase 1 Dose-Escalation Study of TJ004309 in Combination With Atezolizumab (Tecentriq®) in Patients With Advanced or Metastatic Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tracon Pharmaceuticals Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tracon Pharmaceuticals Inc.</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 multicenter, open label, Phase 1 dose escalation study of TJ004309 in combination&#xD;
      with standard dose atezolizumab in patients with advanced or metastatic cancer in patients&#xD;
      who are refractory to or intolerant to all available therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 16, 2019</start_date>
  <completion_date type="Anticipated">June 2022</completion_date>
  <primary_completion_date type="Anticipated">June 2022</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>Maximum Tolerate Dose of TJ004309 plus Atezolizumab</measure>
    <time_frame>Approximately 2-8 months</time_frame>
    <description>Evaluate safety and tolerability and determine a recommended Phase 2 dose of TJ004309 when combined with standard dose atezolizumab in patients with advanced or metastatic cancer. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 and coded using MedDRA 14.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Determine Phase 2 dose to TJ004309 as a single agent</measure>
    <time_frame>Approximately 2-8 months</time_frame>
    <description>Determine the Phase 2 dose of TJ004309 as a single agent</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough TJ004309 concentrations</measure>
    <time_frame>Approximately 2-8 months</time_frame>
    <description>Trough (pre-dose and post-dose) serum TJ004309 concentrations will be measured when given as a single agent and with atezolizumab</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough atezolizumab concentrations</measure>
    <time_frame>Approximately 2-8 months</time_frame>
    <description>Trough (pre-dose and post-dose) serum atezolizumab concentrations will be measured when given with TJ004309</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the Rate of TJ004309 Immunogenicity</measure>
    <time_frame>Approximately 2-8 months</time_frame>
    <description>The number of patients who develop immunogenicity to TJ004309 (anti-product antibody development) will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the Rate of Atezolizumab Immunogenicity</measure>
    <time_frame>Approximately 2-8 months</time_frame>
    <description>The number of patients who develop immunogenicity to atezolizumab (anti-product antibody development) will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of antitumor activity</measure>
    <time_frame>Approximately 2-8 months</time_frame>
    <description>Antitumor activity will be assessed by the response rate by iRECIST and RECIST 1.1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Solid Tumor</condition>
  <condition>Metastatic Cancer</condition>
  <arm_group>
    <arm_group_label>TJ004309 plus Atezolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TJ004309 will be dose escalated in a 3+3 design in combination with atezolizumab.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TJ004309</intervention_name>
    <description>Antibody to CD73</description>
    <arm_group_label>TJ004309 plus Atezolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Humanized monoclonal antibody to PD-L1</description>
    <arm_group_label>TJ004309 plus Atezolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed advanced or metastatic cancer in patients who are refractory&#xD;
             to or intolerant to all available therapy.&#xD;
&#xD;
          2. Measurable disease by iRECIST&#xD;
&#xD;
          3. Formalin fixed, paraffin-embedded (FFPE) tumor tissue that permits the preparation of&#xD;
             12 unstained slides of tumor sample- Biopsy must be excisional, incisional, or core.&#xD;
             Needle aspiration is insufficient.&#xD;
&#xD;
          4. Age ≥ 18 years&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1&#xD;
&#xD;
          6. Resolution of all acute adverse events resulting from prior cancer therapies to&#xD;
             National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE)&#xD;
             Grade ≤ 1 or baseline (except alopecia or neuropathy)&#xD;
&#xD;
          7. Adequate organ function&#xD;
&#xD;
          8. Willingness and ability to consent for self to participate in study&#xD;
&#xD;
          9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory&#xD;
             tests, and other study procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Autoimmune disease requiring treatment within the past twelve months&#xD;
&#xD;
          2. Condition requiring systemic treatment with either corticosteroids or other&#xD;
             immunosuppressive medications within 14 days prior to study treatment&#xD;
&#xD;
          3. History of or active interstitial lung disease&#xD;
&#xD;
          4. Prior T-cell or NK cell therapy&#xD;
&#xD;
          5. Current treatment on another therapeutic clinical trial&#xD;
&#xD;
          6. Receipt of systemic anticancer therapy, including investigational agents, within 28&#xD;
             days prior to study treatment&#xD;
&#xD;
          7. Major surgical procedure or significant traumatic injury within 4 weeks prior to study&#xD;
             treatment, and must have fully recovered from any such procedure; and no date of&#xD;
             surgery (if applicable) or anticipated need for a major surgical procedure planned&#xD;
             within the next 6 months&#xD;
&#xD;
          8. Chest radiotherapy ≤ 28 days, wide field radiotherapy ≤ 28 days (defined as &gt; 50% of&#xD;
             volume of pelvic bones or equivalent), or limited field radiation for palliation ≤ 14&#xD;
             days prior to study treatment - such patients must have recovered adequately from any&#xD;
             side effects of such therapy.&#xD;
&#xD;
          9. Hypertension defined as blood pressure (BP) systolic &gt; 150 or diastolic &gt; 90 mm Hg&#xD;
&#xD;
         10. Ascites or pericardial effusion that required intervention within 3 months prior to&#xD;
             study treatment.&#xD;
&#xD;
         11. Brain involvement with cancer, spinal cord compression, or carcinomatous meningitis,&#xD;
             or new evidence of brain or leptomeningeal disease, unless the lesion(s) have been&#xD;
             radiated or resected, are considered fully treated and inactive, are asymptomatic, and&#xD;
             no steroids have been administered for CNS disease over the 7 days prior to study&#xD;
             treatment&#xD;
&#xD;
         12. Angina, myocardial infarction (MI), symptomatic congestive heart failure,&#xD;
             cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary&#xD;
             embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery&#xD;
             bypass grafting (CABG) within 6 months prior to study treatment&#xD;
&#xD;
         13. Thrombolytic use (except to maintain IV catheters) within 10 days prior study&#xD;
             treatment&#xD;
&#xD;
         14. Known active viral or nonviral hepatitis or cirrhosis, except patients with Hepatitis&#xD;
             C infection and undetectable virus following treatment are eligible.&#xD;
&#xD;
         15. Any active infection requiring systemic treatment&#xD;
&#xD;
         16. History of hemorrhage or hemoptysis (&gt; ½ teaspoon bright red blood) within 3 months&#xD;
             prior to study treatment&#xD;
&#xD;
         17. Known human immunodeficiency virus (HIV) unless CD4+ T cell count &gt; 350 cells/μL with&#xD;
             an undetectable viral load.&#xD;
&#xD;
         18. Pregnancy or breastfeeding - Female patients must be surgically sterile (i.e., ≥ 6&#xD;
             weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal&#xD;
             ligation) or be postmenopausal for at least one year, or must agree to use effective&#xD;
             contraception during the study and for 5 months following last dose of TJ004309. All&#xD;
             female patients of reproductive potential must have a negative pregnancy test (serum&#xD;
             or urine) within 7 days prior to study treatment. Male patients must be surgically&#xD;
             sterile or must agree to use effective contraception during the study and for 5 months&#xD;
             following last dose of TJ004309.&#xD;
&#xD;
         19. Patients with any severe infection within 4 weeks prior to initiation of study&#xD;
             treatment, including, but not limited to, hospitalization for complications of&#xD;
             infections should not be enrolled in the trial. Patients who required IV antibiotics&#xD;
             or were treated with antiviral medications within this 4 week period should be&#xD;
             discussed with the TRACON prior to enrollment.&#xD;
&#xD;
         20. Other severe acute or chronic medical or psychiatric condition or laboratory&#xD;
             abnormality that may increase the risk associated with study participation or may&#xD;
             interfere with the interpretation of study results and, in the judgment of the&#xD;
             Investigator, would make the patient inappropriate for this 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>
  <overall_official>
    <last_name>Charles Theuer, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Medical Monitor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HonorHealth Research Institute</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.traconpharma.com</url>
    <description>TRACON Pharmaceuticals</description>
  </link>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>February 5, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>March 31, 2022</last_update_submitted>
  <last_update_submitted_qc>March 31, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2022</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>Neoplasm Metastasis</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Neoplasms, Second Primary</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>September 16, 2022</submitted>
  </pending_results>
  <!-- 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/NCT03835949
org study id: 4309ST101
nct id: NCT03835949
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a multicenter, open label, Phase 1 dose escalation study of TJ004309 in combination
      with standard dose atezolizumab in patients with advanced or metastatic cancer in patients
      who are refractory to or intolerant to all available therapy.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerate Dose of TJ004309 plus Atezolizumab
time frame: Approximately 2-8 months
description: Evaluate safety and tolerability and determine a recommended Phase 2 dose of TJ004309 when combined with standard dose atezolizumab in patients with advanced or metastatic cancer. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 and coded using MedDRA 14.1.
measure: Determine Phase 2 dose to TJ004309 as a single agent
time frame: Approximately 2-8 months
description: Determine the Phase 2 dose of TJ004309 as a single agent
measure: Trough TJ004309 concentrations
time frame: Approximately 2-8 months
description: Trough (pre-dose and post-dose) serum TJ004309 concentrations will be measured when given as a single agent and with atezolizumab
measure: Trough atezolizumab concentrations
time frame: Approximately 2-8 months
description: Trough (pre-dose and post-dose) serum atezolizumab concentrations will be measured when given with TJ004309
measure: Determine the Rate of TJ004309 Immunogenicity
time frame: Approximately 2-8 months
description: The number of patients who develop immunogenicity to TJ004309 (anti-product antibody development) will be determined.
measure: Determine the Rate of Atezolizumab Immunogenicity
time frame: Approximately 2-8 months
description: The number of patients who develop immunogenicity to atezolizumab (anti-product antibody development) will be determined.
measure: Assessment of antitumor activity
time frame: Approximately 2-8 months
description: Antitumor activity will be assessed by the response rate by iRECIST and RECIST 1.1
arm group label: TJ004309 plus Atezolizumab
arm group type: Experimental
description: TJ004309 will be dose escalated in a 3+3 design in combination with atezolizumab.
intervention type: Drug
intervention name: TJ004309
description: Antibody to CD73
arm group label: TJ004309 plus Atezolizumab
intervention type: Drug
intervention name: Atezolizumab
description: Humanized monoclonal antibody to PD-L1
arm group label: TJ004309 plus Atezolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Charles Theuer, MD, PhD
role: Study Director
affiliation: Medical Monitor
facility: 
facility: 
facility: 
facility: 
country: United States
url: http://www.traconpharma.com
description: TRACON Pharmaceuticals
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Neoplasms
mesh term: Neoplasms, Second Primary
mesh term: Atezolizumab
sharing ipd: No
submitted: September 16, 2022