<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/NCT04502082</url>
  </required_header>
  <id_info>
    <org_study_id>ETUS19AFPAR121</org_study_id>
    <nct_id>NCT04502082</nct_id>
  </id_info>
  <brief_title>Study of ET140203 T Cells in Adults With Advanced Hepatocellular Carcinoma (ARYA-1)</brief_title>
  <official_title>An Open-Label, Dose Escalation, Multi-Center Phase I/II Research Trial to Assess the Safety of ET140203 T Cells and Determine the Recommended Phase II Dose (RP2D) in Adults With Advanced Hepatocellular Carcinoma (HCC) (ARYA-1)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Eureka Therapeutics Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Eureka Therapeutics Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Open-label, dose escalation, multi-center, Phase I / II study to assess the safety of an&#xD;
      autologous T-cell product (ET140203) in adult subjects with Alpha-fetoprotein&#xD;
      (AFP)-positive/Human Leukocyte Antigen (HLA) A-2-positive advanced hepatocellular carcinoma&#xD;
      (HCC).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to investigate an autologous T-cell therapy for advanced&#xD;
      hepatocellular carcinoma (HCC). ET140203 T cells are autologous T cells genetically modified&#xD;
      to carry a TCR-mimic (TCRm) construct capable of mediating cell killing by targeting tumor&#xD;
      specific intracellular antigens and addressing solid tumor therapy challenges.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 14, 2021</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">January 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Sequential Assignment</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence rates of adverse events (AEs) after infusion of ET140203 T cells</measure>
    <time_frame>28 days</time_frame>
    <description>Safety of ET140203T cells as assessed by the number of adverse events (AEs) after infusion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity rates of adverse events (AEs) after infusion of ET140203 T cells</measure>
    <time_frame>28 days</time_frame>
    <description>Safety of ET140203T cells as assessed by the severity of adverse events (AEs) after infusion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells</measure>
    <time_frame>28 days</time_frame>
    <description>Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT</measure>
    <time_frame>up to 2 years</time_frame>
    <description>The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLT, and secondarily on the best tumor response</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assess the efficacy of ET140203 T cells in adults with advanced HCC.</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Determine the pharmacokinetics of ET140203 T cells after infusion.</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Assess the persistence of ET140203 T cells circulating in blood over time</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Liver Cancer</condition>
  <condition>Liver Neoplasm</condition>
  <condition>Metastatic Liver Cancer</condition>
  <arm_group>
    <arm_group_label>ET140203 TCells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ET140203 T Cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ET140203 autologous T cell product</intervention_name>
    <description>Autologous T cells transduced with lentivirus encoding an ET140203 expression construct</description>
    <arm_group_label>ET140203 TCells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed HCC with serum AFP &gt;100ng/ml at time of screening and&#xD;
             following most current line of therapy OR radiographic diagnosis of HCC with serum AFP&#xD;
             &gt;400ng/ml at time of screening and following most current line of therapy.&#xD;
&#xD;
          -  Metastatic or locally advanced, unresectable HCC&#xD;
&#xD;
          -  Must have failed or not tolerated at least two (2) different anti-HCC systemic agents&#xD;
&#xD;
          -  Molecular Human Leukocyte Antigen (&quot;HLA&quot;) class I allele typing confirms participant&#xD;
             carries at least one HLA-A2 allele&#xD;
&#xD;
          -  Life expectancy of at least 4 months&#xD;
&#xD;
          -  Karnofsky Performance Scale greater than or equal to 70&#xD;
&#xD;
          -  At least 1 measurable lesion on imaging by RECIST&#xD;
&#xD;
          -  Child-Pugh A6 or better&#xD;
&#xD;
          -  Absolute neutrophil count greater than or equal to 1,500/mm^3&#xD;
&#xD;
          -  Platelet count greater than or equal to 75,000/mm^3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant cardiac disease&#xD;
&#xD;
          -  Clinically significant pre-existing illness or active infection&#xD;
&#xD;
          -  Clinically significant Central Nervous System (CNS) or neural dysfunction&#xD;
&#xD;
          -  Active autoimmune disease requiring therapy&#xD;
&#xD;
          -  Active malignancy other than HCC with the exception of cholangiocarcinoma (CCA) or any&#xD;
             malignancy with an expected survival ≥ 3 years without any treatment (exception:&#xD;
             hormone/androgen-deprivation therapy) and without any organ involvement&#xD;
&#xD;
          -  History of organ transplant&#xD;
&#xD;
          -  Compromised circulation in portal vein, hepatic vein, or vena cava due to obstruction&#xD;
&#xD;
          -  Advanced HCC involving greater than 50% of the liver&#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>Pei Wang, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Eureka Therapeutics Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Teresa Klask, BS</last_name>
    <phone>510-722-8719</phone>
    <phone_ext>412</phone_ext>
    <email>Teresa.Klask@eurekainc.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Pei Wang, PhD</last_name>
    <phone>510-972-1252</phone>
    <email>Pei.Wang@eurekainc.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Claudia Aceves (Clinical Research Coordinator)</last_name>
      <phone>626-218-5114</phone>
      <email>CAceves@coh.org</email>
    </contact>
    <investigator>
      <last_name>Daneng Li, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Kansas University Medical Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Anna Davis</last_name>
      <phone>913-588-0242</phone>
      <email>adavis43@kumc.edu</email>
    </contact>
    <investigator>
      <last_name>Raed Al-Rajabi, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>May 31, 2023</last_update_submitted>
  <last_update_submitted_qc>May 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatocellular Carcinoma HCC</keyword>
  <keyword>Advanced HCC</keyword>
  <keyword>Late-Stage HCC</keyword>
  <keyword>Liver Cancer</keyword>
  <keyword>Liver Neoplasm</keyword>
  <keyword>Metastatic Liver Cancer</keyword>
  <keyword>Metastatic HCC</keyword>
  <keyword>T-cell therapy</keyword>
  <keyword>Immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Liver Neoplasms</mesh_term>
  </condition_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/NCT04502082
org study id: ETUS19AFPAR121
nct id: NCT04502082
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
Open-label, dose escalation, multi-center, Phase I / II study to assess the safety of an
      autologous T-cell product (ET140203) in adult subjects with Alpha-fetoprotein
      (AFP)-positive/Human Leukocyte Antigen (HLA) A-2-positive advanced hepatocellular carcinoma
      (HCC).
The purpose of this study is to investigate an autologous T-cell therapy for advanced
      hepatocellular carcinoma (HCC). ET140203 T cells are autologous T cells genetically modified
      to carry a TCR-mimic (TCRm) construct capable of mediating cell killing by targeting tumor
      specific intracellular antigens and addressing solid tumor therapy challenges.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence rates of adverse events (AEs) after infusion of ET140203 T cells
time frame: 28 days
description: Safety of ET140203T cells as assessed by the number of adverse events (AEs) after infusion
measure: Severity rates of adverse events (AEs) after infusion of ET140203 T cells
time frame: 28 days
description: Safety of ET140203T cells as assessed by the severity of adverse events (AEs) after infusion.
measure: Incidence rates of dose limiting toxicities (DLTs) after infusion of ET140203 T cells
time frame: 28 days
description: Tolerability of ET140203T cells after infusions assessed by committee review of dose limiting toxicities (DLTs)
measure: The recommended phase 2 dose (RP2D) regimen of ET140203 T-cell therapy primarily based on DLT
time frame: up to 2 years
description: The RP2D will be determined by the study Dose Escalation Committee (DEC) and primarily based on DLT, and secondarily on the best tumor response
measure: Assess the efficacy of ET140203 T cells in adults with advanced HCC.
time frame: up to 2 years
description: Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.
measure: Determine the pharmacokinetics of ET140203 T cells after infusion.
time frame: up to 2 years
description: Assess the persistence of ET140203 T cells circulating in blood over time
arm group label: ET140203 TCells
arm group type: Experimental
description: ET140203 T Cells
intervention type: Biological
intervention name: ET140203 autologous T cell product
description: Autologous T cells transduced with lentivirus encoding an ET140203 expression construct
arm group label: ET140203 TCells
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Pei Wang, PhD
role: Study Director
affiliation: Eureka Therapeutics Inc.
last name: Teresa Klask, BS
phone: 510-722-8719
phone ext: 412
email: Teresa.Klask@eurekainc.com
last name: Pei Wang, PhD
phone: 510-972-1252
email: Pei.Wang@eurekainc.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Hepatocellular
mesh term: Liver Neoplasms
sharing ipd: No