<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/NCT02223247</url>
  </required_header>
  <id_info>
    <org_study_id>3V2640-CLIN-002</org_study_id>
    <nct_id>NCT02223247</nct_id>
  </id_info>
  <brief_title>A Phase 1, First-In-Human Study of Escalating Doses of Oral TVB-2640 in Patients With Solid Tumors</brief_title>
  <official_title>A Phase 1, First-In-Human Study of Escalating Doses of Oral TVB-2640 in Patients With Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sagimet Biosciences Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sagimet Biosciences 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>
      This first in human phase 1 study of TVB-2640 is being conducted in patients with advanced&#xD;
      stage solid malignant tumors. This research is being done to find out how safe and useful&#xD;
      TVB-2640 is for patients who have received previous cancer therapy, and for whom no therapy&#xD;
      exists that would be curative or might provide significant benefit. TVB-2640 belongs to a&#xD;
      class of drugs called fatty acid synthase inhibitors (FASN inhibitors). This means that they&#xD;
      interfere with the body's (and the tumor's) ability to use a substance called fatty acid&#xD;
      synthase (FASN). Research has shown that some tumors appear to need FASN to keep growing.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2013</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</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>To determine the maximum tolerated dose (MTD) based on toxicity analysis.</measure>
    <time_frame>1.5 years</time_frame>
    <description>Toxicity will be monitored according to NCI - Common Toxicity Criteria for Adverse Events version (4.03). Patients receiving at least one dose of drug.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the incidence and nature of dose-limiting toxicities (DLTs) of TVB-2640.</measure>
    <time_frame>Days 1 to 21 of cycle 1 for monotherapy cohort(s); Days 1 to 28 of cycle 1 for combination with anti-cancer agent cohort(s)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence, nature and severity of adverse events and serious adverse events, graded according to NCI - Common Toxicity Criteria for Adverse Events version (4.03).</measure>
    <time_frame>Up to 28 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic parameters of TVB-2640 (including total exposure, maximum and minimum serum concentration, clearance, volume of distribution at steady state)</measure>
    <time_frame>At Cycle Day 1, 2, 8, 15, (and 22 for combination cohorts) then the first day of subsequent cycles until discontinuation.</time_frame>
    <description>Cmax, Cmin, Tmax, AUC and Half-life of TVB-2640</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response per RECIST 1.1</measure>
    <time_frame>Measured every 6 weeks for 21 day cycles or every 8 weeks for 28 day cycles for the duration of study treatment, estimated to be less than one year</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Solid Malignant Tumor</condition>
  <arm_group>
    <arm_group_label>TVB-2640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral TVB-2640 capsules or tablets of various dose strengths administered QD for 21 - 28 day dosing cycles, alone or in combination with certain standard chemotherapy agents</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TVB-2640</intervention_name>
    <arm_group_label>TVB-2640</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria Include:&#xD;
&#xD;
          -  Patient has histologically- or cytologically- confirmed metastatic or advanced-stage&#xD;
             solid malignant tumor that is refractory to standard therapy and for whom no therapy&#xD;
             exists that would be curative or might provide significant benefit and therefore for&#xD;
             whom experimental therapy is a reasonable option.&#xD;
&#xD;
          -  Patient experienced progressive disease during or following or was intolerant of their&#xD;
             most recent treatment regimen.&#xD;
&#xD;
          -  Patient is male or female aged ≥18 years.&#xD;
&#xD;
          -  Patient has an ECOG performance status of 0 (fully active, able to carry out all&#xD;
             pre-disease activities without restriction) or 1 (unable to perform physically&#xD;
             strenuous activity but ambulatory and able to carry out work of a light or sedentary&#xD;
             nature), as assessed on C1D1, before the first dose of TVB 2640.&#xD;
&#xD;
          -  Patient has adequate renal function (creatinine ≤1.5 times the upper limit of normal&#xD;
             [ULN]) or a glomerular filtration rate (GFR) of ≥50 mL/min.&#xD;
&#xD;
          -  Patient has adequate hepatic function,&#xD;
&#xD;
          -  Patient has adequate bone marrow function&#xD;
&#xD;
          -  Patient has no significant ischemic heart disease or myocardial infarction (MI) within&#xD;
             6 months before the first dose of TVB 2640 and currently has adequate cardiac function&#xD;
&#xD;
        For the Monotherapy Expansion Cohorts of the Study ONLY:&#xD;
&#xD;
          -  Patient has a specific tumor-type and histology, as designated by the Sponsor based on&#xD;
             nonclinical and clinical data obtained prior to enrollment in the Expansion Cohort.&#xD;
&#xD;
          -  Patient has measurable disease, as determined by the Investigator using RECIST,&#xD;
             version 1.1 (1).&#xD;
&#xD;
        For the Combination Cohorts ONLY:&#xD;
&#xD;
          -  In addition to meeting monotherapy criteria above, the commercially-available&#xD;
             anticancer agent of interest being investigated in combination with TVB-2640,&#xD;
             administered according to the dose regimen in the prescribing information, is deemed&#xD;
             appropriate for the patient's disease and clinical status.&#xD;
&#xD;
        Exclusion Criteria Include:&#xD;
&#xD;
          -  Patient is unable to swallow oral medications or has impairment of GI function or GI&#xD;
             disease that may significantly alter drug absorption&#xD;
&#xD;
          -  Patient has uncontrolled or severe intercurrent medical condition (including&#xD;
             uncontrolled brain metastases).&#xD;
&#xD;
          -  Patient underwent major surgery within 4 weeks before the first dose of TVB 2640 or&#xD;
             received cancer-directed therapy or an investigational drug or device within 4 weeks&#xD;
             (6 weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent (whichever is&#xD;
             shorter) before the first dose of TVB 2640.&#xD;
&#xD;
          -  If female, patient is pregnant or breast-feeding.&#xD;
&#xD;
          -  Patient has evidence of a serious active infection&#xD;
&#xD;
          -  Patient has a history of other malignancy treated with curative intent within the&#xD;
             previous 5 years with the exception of adequately treated non-melanoma skin cancer or&#xD;
             carcinoma in situ of the cervix.&#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>Jeffrey R Infante, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Sarah Cannon Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80218</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charthouse Square, London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>London</city>
        <zip>W1G 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Manchester</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>West Smithfield, London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 18, 2014</study_first_submitted>
  <study_first_submitted_qc>August 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2014</study_first_posted>
  <last_update_submitted>August 11, 2017</last_update_submitted>
  <last_update_submitted_qc>August 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>solid tumors</keyword>
  <keyword>cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>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/NCT02223247
org study id: 3V2640-CLIN-002
nct id: NCT02223247
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This first in human phase 1 study of TVB-2640 is being conducted in patients with advanced
      stage solid malignant tumors. This research is being done to find out how safe and useful
      TVB-2640 is for patients who have received previous cancer therapy, and for whom no therapy
      exists that would be curative or might provide significant benefit. TVB-2640 belongs to a
      class of drugs called fatty acid synthase inhibitors (FASN inhibitors). This means that they
      interfere with the body's (and the tumor's) ability to use a substance called fatty acid
      synthase (FASN). Research has shown that some tumors appear to need FASN to keep growing.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To determine the maximum tolerated dose (MTD) based on toxicity analysis.
time frame: 1.5 years
description: Toxicity will be monitored according to NCI - Common Toxicity Criteria for Adverse Events version (4.03). Patients receiving at least one dose of drug.
measure: To determine the incidence and nature of dose-limiting toxicities (DLTs) of TVB-2640.
time frame: Days 1 to 21 of cycle 1 for monotherapy cohort(s); Days 1 to 28 of cycle 1 for combination with anti-cancer agent cohort(s)
measure: Incidence, nature and severity of adverse events and serious adverse events, graded according to NCI - Common Toxicity Criteria for Adverse Events version (4.03).
time frame: Up to 28 days after the last dose of study treatment or until initiation of another anti-cancer therapy, whichever occurs first.
measure: Pharmacokinetic parameters of TVB-2640 (including total exposure, maximum and minimum serum concentration, clearance, volume of distribution at steady state)
time frame: At Cycle Day 1, 2, 8, 15, (and 22 for combination cohorts) then the first day of subsequent cycles until discontinuation.
description: Cmax, Cmin, Tmax, AUC and Half-life of TVB-2640
measure: Tumor response per RECIST 1.1
time frame: Measured every 6 weeks for 21 day cycles or every 8 weeks for 28 day cycles for the duration of study treatment, estimated to be less than one year
arm group label: TVB-2640
arm group type: Experimental
description: Oral TVB-2640 capsules or tablets of various dose strengths administered QD for 21 - 28 day dosing cycles, alone or in combination with certain standard chemotherapy agents
intervention type: Drug
intervention name: TVB-2640
arm group label: TVB-2640
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey R Infante, MD
role: Principal Investigator
affiliation: The Sarah Cannon Research Institute
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
facility: 
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country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Neoplasms