xml: <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/NCT06005740</url>
    </required_header>
    <id_info>
      <org_study_id>TORL4500-001</org_study_id>
      <nct_id>NCT06005740</nct_id>
    </id_info>
    <brief_title>First in Human Study of TORL-4-500 in Participants With Advanced Cancer</brief_title>
    <official_title>A Phase 1, First in Human, Dose-Escalation Study of TORL-4-500 in Participants With Advanced Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>TORL Biotherapeutics, LLC</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Translational Research in Oncology</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>TORL Biotherapeutics, LLC</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 first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and&#xD;
        antitumor activity of TORL-4-500 in patients with advanced cancer&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 31, 2023</start_date>
    <completion_date type="Anticipated">October 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 31, 2025</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence and severity of adverse events and serious adverse events</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Maximum Tolerated Dose (MTD)</measure>
      <time_frame>28 Days</time_frame>
      <description>Highest administered dose with &lt; 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Recommended Phase 2 Dose (RP2D)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate (ORR)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Time from CR or PR to objective disease progression or death to any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression Free Survival (PFS)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to Response (TTR)</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Time from start of treatment to complete response or partial response</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>1 Year Overall Survival (1YOS)</measure>
      <time_frame>1 year</time_frame>
      <description>Proportion of participants alive at 1 year from the start of treatment to death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>2 Year Overall Survival (2YOS)</measure>
      <time_frame>2 years</time_frame>
      <description>Proportion of participants alive at 2 years from the start of treatment to death from any cause</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of anti-drug antibody (ADA) Positive Participants</measure>
      <time_frame>up to 2 years</time_frame>
      <description>Immunogenicity will be measured by the number of participants that are ADA positive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum Serum Concentration of TORL-4-500 (Cmax)</measure>
      <time_frame>21 days</time_frame>
      <description>PK assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Minimum Serum Concentration of TORL-4-500 (Cmin)</measure>
      <time_frame>21 days</time_frame>
      <description>PK assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum Serum Concentration of TORL-4-500 at Steady State (Cmax,ss)</measure>
      <time_frame>63 days</time_frame>
      <description>PK assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Minimum Serum Concentration of TORL-4-500 at Steady State (Cmin,ss)</measure>
      <time_frame>63 days</time_frame>
      <description>PK assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time of Maximum Serum Concentration of TORL-4-500 (Tmax)</measure>
      <time_frame>21 days</time_frame>
      <description>PK assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time of Minimum Serum Concentration of TORL-4-500 (Tmin)</measure>
      <time_frame>21 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time of Minimum Serum Concentration of TORL-4-500 at Steady State (Tmin,ss)</measure>
      <time_frame>63 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Terminal Half-life (t1/2) of Serum TORL-4-500-ADC</measure>
      <time_frame>63 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUClast) for TORL-1-23</measure>
      <time_frame>21 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUCinf) for TORL-1-23</measure>
      <time_frame>63 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apparent volume of distribution during the terminal phase (Vz) of TORL-4-500</measure>
      <time_frame>63 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clearance (CL) of TORL-4-500</measure>
      <time_frame>63 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Accumulation ratio (Rac) of TORL-4-500</measure>
      <time_frame>63 days</time_frame>
      <description>PK Assessment</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">70</enrollment>
    <condition>Advanced Solid Tumor</condition>
    <condition>Hepatocellular Carcinoma</condition>
    <arm_group>
      <arm_group_label>Monotherapy Dose Dose Finding - Part 1</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>TORL-4-500 iv once every 3 weeks</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Expansion as Monotherapy - Part 2</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>TORL-4-500 iv once every 3 weeks</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TORL-4-500</intervention_name>
      <description>antibody drug conjugate</description>
      <arm_group_label>Expansion as Monotherapy - Part 2</arm_group_label>
      <arm_group_label>Monotherapy Dose Dose Finding - Part 1</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Advanced solid tumor&#xD;
  &#xD;
            -  Measurable disease, per RECIST v1.1&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1&#xD;
  &#xD;
            -  Adequate organ function&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Has not recovered [recovery is defined as NCI CTCAE, version 5.0, grade ≤1] from the&#xD;
               acute toxicities of previous therapy, except treatment-related alopecia or laboratory&#xD;
               abnormalities otherwise meeting eligibility requirements&#xD;
  &#xD;
            -  Received prior chemotherapeutic, investigational, or other therapies for the treatment&#xD;
               of cancer within 14 days with small molecule and within 28 days with biologic before&#xD;
               the first dose of TORL-4-500&#xD;
  &#xD;
            -  Progressive or symptomatic brain metastases&#xD;
  &#xD;
            -  Serious, uncontrolled medical disorder, nonmalignant systemic disease, or active,&#xD;
               uncontrolled infection&#xD;
  &#xD;
            -  History of significant cardiac disease&#xD;
  &#xD;
            -  History of myelodysplastic syndrome (MDS) or AML&#xD;
  &#xD;
            -  History of another cancer within 3 years before Day 1 of study treatment, with the&#xD;
               exception of basal or squamous cell carcinoma of the skin that has been definitively&#xD;
               treated. A history of other malignancies with a low risk of recurrence, including&#xD;
               appropriately treated ductal carcinoma in situ (DCIS) of the breast and prostate&#xD;
               cancer with a Gleason score less than or equal to 6, are also not excluded&#xD;
  &#xD;
            -  If female, is pregnant or breastfeeding&#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>Stephen Letrent, PharmD, PhD</last_name>
      <role>Study Director</role>
      <affiliation>TORL Biotherapeutics, LLC</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Stephen Letrent, PharmD, PhD</last_name>
      <phone>858-342-6652</phone>
      <email>stephen.letrent@torlbio.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>UCLA - JCCC Clinical Research Unit</name>
        <address>
          <city>Los Angeles</city>
          <state>California</state>
          <zip>90095</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Lee Rosen, MD</last_name>
        <phone>310-829-5471</phone>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 15, 2023</study_first_submitted>
    <study_first_submitted_qc>August 15, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>ADC</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06005740
  org study id: TORL4500-001
  nct id: NCT06005740
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  This first-in-human study will evaluate the safety, tolerability, pharmacokinetics, and
        antitumor activity of TORL-4-500 in patients with advanced cancer
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence and severity of adverse events and serious adverse events
  time frame: up to 2 years
  description: Incidence and severity of adverse events, serious adverse events, according to NCI-CTCAE Version 5.0
  measure: Maximum Tolerated Dose (MTD)
  time frame: 28 Days
  description: Highest administered dose with < 33% participants experiencing dose limiting toxicity (DLT) in the first 6 DLT evaluable participants
  measure: Recommended Phase 2 Dose (RP2D)
  time frame: up to 2 years
  description: Based on the maximum tolerated dose, cumulative safety, and pharmacokinetic data
  measure: Objective Response Rate (ORR)
  time frame: up to 2 years
  description: Percentage of participants with best response of complete response (CR) or partial response (PR) according to RECIST 1.1
  measure: Duration of Response (DOR)
  time frame: up to 2 years
  description: Time from CR or PR to objective disease progression or death to any cause
  measure: Progression Free Survival (PFS)
  time frame: up to 2 years
  description: PFS is defined as the time from the start of the treatment until objective disease progression or death from any cause
  measure: Time to Response (TTR)
  time frame: up to 2 years
  description: Time from start of treatment to complete response or partial response
  measure: 1 Year Overall Survival (1YOS)
  time frame: 1 year
  description: Proportion of participants alive at 1 year from the start of treatment to death from any cause
  measure: 2 Year Overall Survival (2YOS)
  time frame: 2 years
  description: Proportion of participants alive at 2 years from the start of treatment to death from any cause
  measure: Number of anti-drug antibody (ADA) Positive Participants
  time frame: up to 2 years
  description: Immunogenicity will be measured by the number of participants that are ADA positive.
  measure: Maximum Serum Concentration of TORL-4-500 (Cmax)
  time frame: 21 days
  description: PK assessment
  measure: Minimum Serum Concentration of TORL-4-500 (Cmin)
  time frame: 21 days
  description: PK assessment
  measure: Maximum Serum Concentration of TORL-4-500 at Steady State (Cmax,ss)
  time frame: 63 days
  description: PK assessment
  measure: Minimum Serum Concentration of TORL-4-500 at Steady State (Cmin,ss)
  time frame: 63 days
  description: PK assessment
  measure: Time of Maximum Serum Concentration of TORL-4-500 (Tmax)
  time frame: 21 days
  description: PK assessment
  measure: Time of Minimum Serum Concentration of TORL-4-500 (Tmin)
  time frame: 21 days
  description: PK Assessment
  measure: Time of Minimum Serum Concentration of TORL-4-500 at Steady State (Tmin,ss)
  time frame: 63 days
  description: PK Assessment
  measure: Terminal Half-life (t1/2) of Serum TORL-4-500-ADC
  time frame: 63 days
  description: PK Assessment
  measure: Area under the Serum Concentration-Time curve from the time of dosing to the last measurable concentration (AUClast) for TORL-1-23
  time frame: 21 days
  description: PK Assessment
  measure: Area under the Serum Concentration-Time curve from the time of dosing extrapolated to time infinity (AUCinf) for TORL-1-23
  time frame: 63 days
  description: PK Assessment
  measure: Apparent volume of distribution during the terminal phase (Vz) of TORL-4-500
  time frame: 63 days
  description: PK Assessment
  measure: Clearance (CL) of TORL-4-500
  time frame: 63 days
  description: PK Assessment
  measure: Accumulation ratio (Rac) of TORL-4-500
  time frame: 63 days
  description: PK Assessment
  arm group label: Monotherapy Dose Dose Finding - Part 1
  arm group type: Experimental
  description: TORL-4-500 iv once every 3 weeks
  arm group label: Expansion as Monotherapy - Part 2
  arm group type: Experimental
  description: TORL-4-500 iv once every 3 weeks
  intervention type: Drug
  intervention name: TORL-4-500
  description: antibody drug conjugate
  arm group label: Expansion as Monotherapy - Part 2
  arm group label: Monotherapy Dose Dose Finding - Part 1
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Stephen Letrent, PharmD, PhD
  role: Study Director
  affiliation: TORL Biotherapeutics, LLC
  last name: Stephen Letrent, PharmD, PhD
  phone: 858-342-6652
  email: stephen.letrent@torlbio.com
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma, Hepatocellular
  sharing ipd: No