<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/NCT03808558</url>
  </required_header>
  <id_info>
    <org_study_id>STU 022017-058</org_study_id>
    <nct_id>NCT03808558</nct_id>
  </id_info>
  <brief_title>Phase 2 Study of TVB-2640 in KRAS Non-Small Cell Lung Carcinomas</brief_title>
  <official_title>A Phase 2 Multi-center Pharmacodynamics Study of TVB-2640 in KRAS Mutant Non-small Cell Lung Carcinomas</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>David E Gerber</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sagimet Biosciences Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cancer Prevention Research Institute of Texas</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</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 is a prospective one-arm, two-stage phase 2 trial of TVB-2640 in KRAS mutant NSCLC&#xD;
      patients. 13 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8&#xD;
      weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with stable disease or partial/complete remissions will continue therapy.&#xD;
&#xD;
      The endpoints are response rate-RR, disease control rate-DCR, PFS-progression-free survival,&#xD;
      CTCAEv5.0 toxicities, plasma lipid levels, collection of sebaceous secretion via Sebutape,&#xD;
      and 11C-acetate PET tumor imaging.&#xD;
&#xD;
      In the first stage, 13 patients will be enrolled. If fewer than 2 patients achieve response,&#xD;
      the study will be stopped. If 2 or more patients have a radiographic response, an additional&#xD;
      21 patients will be enrolled , for a total accrual of 34 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 11, 2019</start_date>
  <completion_date type="Anticipated">December 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <phase>Phase 2</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>Disease control rate of TVB-2640</measure>
    <time_frame>every 8 weeks through study completion, an average of 1 year</time_frame>
    <description>Determine Disease control rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response rate of TVB-2640</measure>
    <time_frame>every 8 weeks through study completion, an average of 1 year</time_frame>
    <description>Determine response rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety profile of TVB-2640</measure>
    <time_frame>Pretreatment and four weeks of treatment.</time_frame>
    <description>Secondary endpoints are 11C-acetate tumor uptake pretreatment and at four weeks of treatment and plasma lipidomics pretreatment and at four weeks of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Establish the predictive value of 11C-acetate PET</measure>
    <time_frame>Pretreatment and four weeks of treatment.</time_frame>
    <description>To establish the predictive value of 11C-acetate PET pretreatment and post-treatment tumor uptake for disease control rate and response rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in fasting plasma lipidomics</measure>
    <time_frame>Pretreatment and four weeks of treatment.</time_frame>
    <description>Blood samples for fasting plasma lipidomics will be collected at baseline and four weeks of treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean change in sebaceous secretion of fatty acids</measure>
    <time_frame>Pretreatment and four weeks of treatment.</time_frame>
    <description>Sebutabe collection of sebaceous secretion of fatty acids will be performed at baseline and four weeks of treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">34</enrollment>
  <condition>KRAS Gene Mutation</condition>
  <arm_group>
    <arm_group_label>TVB-2640</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TVB-2640</intervention_name>
    <description>TVB-2640 will be administered 100mg/m2 orally once a day for 8 weeks.</description>
    <arm_group_label>TVB-2640</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion:&#xD;
&#xD;
          1. Metastatic or advanced stage, histologically or cytologically confirmed NSCLC and&#xD;
             molecular identification of oncogenic KRAS mutation.&#xD;
&#xD;
               -  KRAS mutant NSCLC must be refractory, relapsed, and previously treated with&#xD;
                  doublet chemotherapy and immune checkpoint inhibitor (unless there is a specific&#xD;
                  contraindication to checkpoint inhibitor).&#xD;
&#xD;
               -  Molecular characterization (tissue- or blood-based [ie, cell-free/circulating&#xD;
                  tumor DNA]) must have been performed and must have demonstrated an oncogenic KRAS&#xD;
                  mutation (e.g., exon 12, 13, 61, or 117 mutation detected by sequencing) by a&#xD;
                  CLIA-certified assay (source documentation required). KRAS mutations at other&#xD;
                  codons require review and approval by Study Chair.&#xD;
&#xD;
          2. Subjects' EGFR mutation and ALK gene rearrangement status must be known prior to study&#xD;
             entry. Subjects with EGFR mutation or ALK gene rearrangement must have progressed&#xD;
             after appropriate FDA-approved targeted therapy options prior to eligibility.&#xD;
&#xD;
          3. Patient has evidence of disease progression on most recent line of therapy.&#xD;
&#xD;
          4. Patient has measurable disease by RECIST v1.1 (Eisenhauer, 2009).&#xD;
&#xD;
          5. Age ≥ 18 years.&#xD;
&#xD;
          6. ECOG performance status of 0 or 1.&#xD;
&#xD;
          7. Predicted life expectancy of &gt;3 months.&#xD;
&#xD;
          8. Adequate organ and marrow function as defined below:&#xD;
&#xD;
               -  absolute neutrophil count ≥ 1,500/mcL&#xD;
&#xD;
               -  platelets ≥ 75,000/mcL&#xD;
&#xD;
               -  total bilirubin &lt;2X institutional upper limit of normal&#xD;
&#xD;
               -  AST and ALT ≤5X institutional upper limit of normal&#xD;
&#xD;
               -  serum creatinine &lt;1.5X institutional upper limit of normal&#xD;
&#xD;
               -  LVEF &gt;50%&#xD;
&#xD;
               -  QTcF &lt;470msec&#xD;
&#xD;
          9. Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for&#xD;
             the duration of study participation, and for 90 days following completion of therapy.&#xD;
             Should a woman become pregnant or suspect she is pregnant while participating in this&#xD;
             study, she should inform her treating physician immediately.&#xD;
&#xD;
               -  A female of child-bearing potential is any woman (regardless of sexual&#xD;
                  orientation, having undergone a tubal ligation, or remaining celibate by choice)&#xD;
                  who meets the following criteria:&#xD;
&#xD;
                    -  Has not undergone a hysterectomy or bilateral oophorectomy; or&#xD;
&#xD;
                    -  Has not been naturally postmenopausal for at least 12 consecutive months&#xD;
                       (i.e., has had menses at any time in the preceding 12 consecutive months).&#xD;
&#xD;
         10. No significant ischemic heart disease or myocardial infarction within 6 months of&#xD;
             first dose of TVB-2640 and with current adequate cardiac function as in 3.1.8.&#xD;
&#xD;
         11. Ability to understand and the willingness to sign a written informed consent.&#xD;
&#xD;
        Exclusion:&#xD;
&#xD;
          1. Patient is unable to swallow oral medications or has impairment of GI function or GI&#xD;
             disease that may significantly alter drug absorption such as active inflammatory bowel&#xD;
             disease, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome.&#xD;
&#xD;
          2. Patient has a history of risk factors for torsade de pointes such as uncontrolled&#xD;
             heart failure, severe hypokalemia with potassium less than 3mM/L, history of long QT&#xD;
             syndrome or require use during study participation of concomitant medications known to&#xD;
             prolong QT/QTc interval.&#xD;
&#xD;
          3. Patients who require use of strong CYP3A4/5 agonists or inhibitors during study&#xD;
             participation.&#xD;
&#xD;
          4. Patient has uncontrolled or severe intercurrent medical condition including&#xD;
             uncontrolled brain metastases. Patients with stable brain metastases either treated or&#xD;
             untreated, on a stable dose of steroids/anticonvulsants, with no dose increase within&#xD;
             4 weeks before the first dose of TVB-2640, and no anticipated dose change, are&#xD;
             allowed.&#xD;
&#xD;
          5. Patient underwent major surgery within 4 weeks before the first dose of TVB-2640 or&#xD;
             received cancer-directed therapy either chemotherapy, radiotherapy, hormonal therapy,&#xD;
             biologic or immunotherapy, etc. or an investigational drug or device within 2 weeks (6&#xD;
             weeks for mitomycin C and nitrosoureas) or 5 half-lives of that agent, whichever is&#xD;
             shorter before the first dose of TVB-2640. In addition, any drug- related toxicity,&#xD;
             with the exception of alopecia, an endocrinopathy controlled with replacement therapy,&#xD;
             or a clinically stable toxicity not expected to increase from study therapy (eg,&#xD;
             cisplatin-associated ototoxicity) should have recovered to &lt;Grade 1.&#xD;
&#xD;
          6. If female, patient is pregnant or breast-feeding.&#xD;
&#xD;
          7. Patient has evidence of a serious active infection-infection requiring treatment with&#xD;
             intravenous antibiotics.&#xD;
&#xD;
          8. Patient has known immunodeficiency virus-HIV or hepatitis B or C infection, as such&#xD;
             patients may be at increased risk for toxicity due to concomitant treatment and&#xD;
             disease-related symptoms may preclude accurate assessment of the safety of TVB-2640.&#xD;
&#xD;
          9. Patient has an important medical illness or abnormal laboratory finding that, in the&#xD;
             Investigator's opinion, would increase the risk of participating in this study.&#xD;
&#xD;
         10. Patients with prior or concurrent malignancy whose natural history or treatment has&#xD;
             the potential to interfere with the safety or efficacy assessment of the&#xD;
             investigational agent.&#xD;
&#xD;
         11. History of clinically significant dry eye (xerophthalmia) or other corneal abnormality&#xD;
             or, if a contact lens wearer, does not agree to abstain from contact lens use from&#xD;
             baseline through the last study drug dose.&#xD;
&#xD;
         12. Patient has a known allergy or hypersensitivity to components of TVB-2640.&#xD;
&#xD;
         13. Patient has a prior history of hypersensitivity, drug/radiation-induced, or other&#xD;
             immune-mediated pneumonitis.&#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>David Gerber, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Professor</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ebele Mbanugo, PhD</last_name>
    <phone>214-648-7097</phone>
    <email>Ebele.mbanugo@UTSouthwestern.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>David Gerber, MD</last_name>
    <email>david.gerber@utsouthwestern.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>UCCC Clinical Trials Office</last_name>
      <phone>513-584-7698</phone>
      <email>Cancer@UCHealth.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390-9179</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Gerber, MD</last_name>
      <phone>214-648-4180</phone>
      <email>David.Gerber@utsouthwestern.edu</email>
    </contact>
    <investigator>
      <last_name>David Gerber, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>May 24, 2018</study_first_submitted>
  <study_first_submitted_qc>January 15, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 17, 2019</study_first_posted>
  <last_update_submitted>August 25, 2023</last_update_submitted>
  <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>David E Gerber</investigator_full_name>
    <investigator_title>PROFESSOR - Internal Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</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/NCT03808558
org study id: STU 022017-058
nct id: NCT03808558
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a prospective one-arm, two-stage phase 2 trial of TVB-2640 in KRAS mutant NSCLC
      patients. 13 patients will be treated with a minimum of 1 cycle of TVB-2640 therapy over 8
      weeks.
Patients with stable disease or partial/complete remissions will continue therapy.

      The endpoints are response rate-RR, disease control rate-DCR, PFS-progression-free survival,
      CTCAEv5.0 toxicities, plasma lipid levels, collection of sebaceous secretion via Sebutape,
      and 11C-acetate PET tumor imaging.

      In the first stage, 13 patients will be enrolled. If fewer than 2 patients achieve response,
      the study will be stopped. If 2 or more patients have a radiographic response, an additional
      21 patients will be enrolled , for a total accrual of 34 patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Disease control rate of TVB-2640
time frame: every 8 weeks through study completion, an average of 1 year
description: Determine Disease control rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.
measure: Response rate of TVB-2640
time frame: every 8 weeks through study completion, an average of 1 year
description: Determine response rate of TVB-2640 in KRAS mutant NSCLC patients through RECIST and toxicity profile.
measure: Safety profile of TVB-2640
time frame: Pretreatment and four weeks of treatment.
description: Secondary endpoints are 11C-acetate tumor uptake pretreatment and at four weeks of treatment and plasma lipidomics pretreatment and at four weeks of treatment.
measure: Establish the predictive value of 11C-acetate PET
time frame: Pretreatment and four weeks of treatment.
description: To establish the predictive value of 11C-acetate PET pretreatment and post-treatment tumor uptake for disease control rate and response rate
measure: Mean change in fasting plasma lipidomics
time frame: Pretreatment and four weeks of treatment.
description: Blood samples for fasting plasma lipidomics will be collected at baseline and four weeks of treatment.
measure: Mean change in sebaceous secretion of fatty acids
time frame: Pretreatment and four weeks of treatment.
description: Sebutabe collection of sebaceous secretion of fatty acids will be performed at baseline and four weeks of treatment
arm group label: TVB-2640
arm group type: Experimental
description: Patients will be administered TVB-2640 100mg/m2 orally once a day for 8 weeks.
intervention type: Drug
intervention name: TVB-2640
description: TVB-2640 will be administered 100mg/m2 orally once a day for 8 weeks.
arm group label: TVB-2640
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: David Gerber, MD
role: Principal Investigator
affiliation: Professor
last name: Ebele Mbanugo, PhD
phone: 214-648-7097
email: Ebele.mbanugo@UTSouthwestern.edu
last name: David Gerber, MD
email: david.gerber@utsouthwestern.edu
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: David E Gerber
investigator title: PROFESSOR - Internal Medicine
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: No