<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/NCT04444427</url>
  </required_header>
  <id_info>
    <org_study_id>GLP-CDK-1009</org_study_id>
    <nct_id>NCT04444427</nct_id>
  </id_info>
  <brief_title>Evaluation of GLR2007 for Advanced Solid Tumors</brief_title>
  <official_title>An Open-Label, Multicenter, Phase 1b/2 Study to Establish Safety, Tolerability, and Optimal Dosing Strategy of GLR2007 in Subjects With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Gan and Lee Pharmaceuticals, USA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Gan and Lee Pharmaceuticals, USA</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>
      Evaluation of GLR2007 for Advanced Solid Tumors&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      An Open-Label, Multicenter, Phase 1b/2 Study to Establish Safety, Tolerability, and Optimal&#xD;
      Dosing Strategy of GLR2007 in Subjects with Advanced Solid Tumors&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Actual">July 29, 2022</completion_date>
  <primary_completion_date type="Actual">July 29, 2022</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>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Part 1 employs a dose-escalation design to determine the recommended phase 2 dose. This is followed by Part 2, which involves parallel dosing of 3 different cohorts at the dose determined in Part 1.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Escalation: Dose-limiting Toxicities</measure>
    <time_frame>Up to 12 Months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Escalation: Incidence And Severity Of Adverse Events, Including The Incidence Of Dose-limiting Toxicities Within The First Cycle</measure>
    <time_frame>Up to 12 Months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Expansion: Incidence And Severity Of Adverse Events</measure>
    <time_frame>Up to 96 Weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation: Objective Response Rate</measure>
    <time_frame>8 Weeks</time_frame>
    <description>Defined by response evaluation criteria in solid tumors (RECIST) Version 1.1 (solid tumors) or by response assessment in neuro-oncology (RANO) (brain metastases and GBM).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Expansion: Objective Response Rate</measure>
    <time_frame>12, 24, 36, 48, 60, 72, 84, and 96 Weeks</time_frame>
    <description>Defined by RECIST Version 1.1 or by RANO as appropriate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation And Expansion: Maximum Observed Plasma Concentration After Single And Multiple Oral Dose Administrations</measure>
    <time_frame>0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation And Expansion: Time At Which Maximum Plasma Concentration Is Observed And Apparent Half-life After Single And Multiple Oral Dose Administrations</measure>
    <time_frame>0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation And Expansion: Area Under The Plasma Concentration-time Curve From 0 To Last Measurable Concentration And From 0 To Infinity After Single And Multiple Oral Dose Administrations</measure>
    <time_frame>0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation And Expansion: Accumulation Ratio After Single And Multiple Oral Dose Administrations</measure>
    <time_frame>0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation And Expansion: Steady-state Volume Of Distribution After Single And Multiple Oral Dose Administrations</measure>
    <time_frame>0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose Escalation And Expansion: Clearance After Single And Multiple Oral Dose Administrations</measure>
    <time_frame>0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <condition>Glioblastoma Multiforme</condition>
  <arm_group>
    <arm_group_label>Part 1: Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation cohorts are planned to determine the maximum tolerated dose or recommended phase 2 dose of GLR-2007, as well as expansion cohorts and a Phase 2 cohort.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Dose Expansion - Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have received 2 or more second-line therapies, with at least 1 line of standard therapy, for their non-small cell lung cancer (NSCLC) will be dosed the maximal tolerated dose of GLR2007 as determined in Part 1 until lack of tolerance or disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Dose Expansion - Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who have received 2 or more second-line therapies, with at least 1 line of standard therapy, for their brain metastases of breast or NSCLC origin will be dosed the maximal tolerated dose of GLR2007 as determined in Part 1 until lack of tolerance or disease progression.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Dose Expansion - Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants experiencing their first recurrence glioblastoma multiforme (GBM) will be dosed the maximal tolerated dose of GLR2007 as determined in Part 1 until lack of tolerance or disease progression.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GLR2007</intervention_name>
    <description>Administered orally, once daily for 21 days followed by a 7-day treatment holiday.</description>
    <arm_group_label>Part 1: Dose Escalation</arm_group_label>
    <arm_group_label>Part 2: Dose Expansion - Cohort A</arm_group_label>
    <arm_group_label>Part 2: Dose Expansion - Cohort B</arm_group_label>
    <arm_group_label>Part 2: Dose Expansion - Cohort C</arm_group_label>
    <other_name>GLR2007-237FA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. For Part 1 (Dose Escalation): Participants with advanced solid tumors who are&#xD;
             refractory or intolerant to therapies known to provide clinical benefit.&#xD;
&#xD;
               1. For Part 1 (Dose Escalation): The participant must have histological or&#xD;
                  cytological evidence of cancer (a solid tumor) that is advanced and/or&#xD;
                  metastatic. Biopsy is allowed by protocol if no histology or cytology records are&#xD;
                  available.&#xD;
&#xD;
               2. For Part 2 (Dose Expansion): The participant must have histological or&#xD;
                  cytological evidence of cancer that is advanced and/or metastatic.&#xD;
&#xD;
          2. For Part 1 (Dose Escalation): The participant has measurable or non-measurable&#xD;
             disease.&#xD;
&#xD;
          3. For Part 2 (Dose Expansion): The participant has measurable disease.&#xD;
&#xD;
          4. The participant has given written informed consent prior to all study-specific&#xD;
             procedures.&#xD;
&#xD;
          5. The participant has adequate hematologic, hepatic, and renal function.&#xD;
&#xD;
          6. The participant has discontinued all prior cancer therapies (including chemotherapy,&#xD;
             immunotherapy, and investigational therapy) for at least 21 days for myelosuppressive&#xD;
             agents or 14 days for radiotherapy and non-myelosuppressive agents, prior to receiving&#xD;
             GLR2007, and has recovered from the acute effects of therapy (treatment related&#xD;
             toxicity resolved to ≤Grade 1) except for residual alopecia.&#xD;
&#xD;
          7. The participant is willing and able to make themselves available for the duration of&#xD;
             the study and is willing and able to follow study procedures.&#xD;
&#xD;
          8. The participant meets contraceptive requirements.&#xD;
&#xD;
          9. The participant has an estimated life expectancy of ≥3 months.&#xD;
&#xD;
         10. The participant agrees to minimize ultraviolet exposure and sunlight for the duration&#xD;
             of their study participation.&#xD;
&#xD;
         11. A diagnostic contrast-enhanced magnetic resonance imaging (MRI) of the brain must be&#xD;
             performed within 28 days prior to registration. Contrast-enhanced computed tomography&#xD;
             (CT) is acceptable if MRI is not possible.&#xD;
&#xD;
        Cohort-specific inclusion criteria Part 2 (Cohort A, NSCLC)&#xD;
&#xD;
          1. Histologically or cytologically confirmed NSCLC.&#xD;
&#xD;
          2. Participants must have received at least 1 line of standard therapy for metastatic&#xD;
             disease, including platinum-based chemotherapy and an immune checkpoint inhibitor&#xD;
             given together or as separate lines of therapy, unless participants are ineligible for&#xD;
             or cannot tolerate such therapy.&#xD;
&#xD;
          3. Participants with anaplastic lymphoma kinase (ALK), epidermal growth factor receptor&#xD;
             (EGFR), proto-oncogene tyrosine-protein kinase ROS (ROS1), v-Raf murine sarcoma viral&#xD;
             oncogene homolog B (BRAF), and neurotrophic receptor tyrosine kinase 1 (NTRK)&#xD;
             aberrations must have received therapy directed at their molecular aberration in order&#xD;
             to enroll on this study.&#xD;
&#xD;
        Part 2 (Cohort B, Brain metastases of breast or NSCLC origin)&#xD;
&#xD;
          1. Histologically or cytologically confirmed NSCLC or breast cancer at primary site.&#xD;
&#xD;
          2. Participants with inoperable brain metastases (prior radiation therapy and/or&#xD;
             stereotactic radiosurgery is allowed). A neurosurgical consult is at the discretion of&#xD;
             the investigator.&#xD;
&#xD;
          3. Participants with brain metastases of NSCLC origin must have received at least 1 line&#xD;
             of standard therapy for metastatic disease, including platinum-based chemotherapy and&#xD;
             an immune checkpoint inhibitor given together or as separate lines of therapy, unless&#xD;
             participants are ineligible for or cannot tolerate such therapy.&#xD;
&#xD;
          4. Participants with ALK, EGFR, ROS1, BRAF, and NTRK aberrations must have received&#xD;
             therapy directed at their molecular aberration in order to enroll on this study.&#xD;
&#xD;
          5. Participants with brain metastases from breast cancer who have previously received&#xD;
             CDK4/6 inhibitors.&#xD;
&#xD;
        Part 2 (Cohort C, GBM)&#xD;
&#xD;
          1. Histologically confirmed diagnosis of a recurrent primary World Health Organization&#xD;
             Grade IV malignant glioblastoma. Participants with recurrent disease whose diagnostic&#xD;
             pathology confirmed glioblastoma will not need re-biopsy. Participants with prior&#xD;
             low-grade glioma or anaplastic glioma are eligible if histologic assessment&#xD;
             demonstrates transformation to GBM.&#xD;
&#xD;
          2. First recurrence of GBM.&#xD;
&#xD;
          3. Candidate for surgical partial or gross-total resection.&#xD;
&#xD;
          4. Radiographic demonstration of disease progression by contrast-enhanced CT or MRI&#xD;
             following prior therapy.&#xD;
&#xD;
          5. At least 2 weeks between prior surgical resection and adequate wound healing.&#xD;
&#xD;
          6. At least 12 weeks from prior radiotherapy unless there is either histopathologic&#xD;
             confirmation of recurrent tumor or new enhancement on MRI outside of the treatment&#xD;
             field.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. The participant has a personal history of any of the following conditions: major&#xD;
             surgical resection involving the stomach or small bowel recurrent, unexplained or&#xD;
             cardiac-related syncopal episodes within the last 6 months or ventricular arrhythmia&#xD;
             (including but not limited to ventricular tachycardia and ventricular fibrillation).&#xD;
&#xD;
          2. Any concurrent malignancies currently requiring treatment or for which treatment would&#xD;
             be deemed necessary within 3 months of enrollment; prostate cancer with androgen&#xD;
             deprivation therapy, basal cell cancer, and squamous cell cancers are allowed.&#xD;
&#xD;
          3. The participant is pregnant or lactating.&#xD;
&#xD;
          4. The participant is immunocompromised and known to be human immunodeficiency virus&#xD;
             positive. The participant has an active bacterial, fungal, and/or known viral&#xD;
             infection (for example, hepatitis B surface antigen or hepatitis C antibodies).&#xD;
&#xD;
        Cohort-specific exclusion criteria:&#xD;
&#xD;
        Part 2 (Cohort A, NSCLC): The participant has NSCLC with worsening symptoms within 14 days&#xD;
        prior to receiving GLR2007.&#xD;
&#xD;
        Part 2 (Cohort B, Brain metastases of breast or NSCLC origin): The participant has CNS&#xD;
        metastasis with worsening symptoms within 14 days prior to receiving GLR2007.&#xD;
&#xD;
        Part 2 (Cohort C, GBM): The participant has GBM with worsening symptoms within 14 days&#xD;
        prior to receiving GLR2007.&#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>Kimberly Lazaroff, MSN</last_name>
    <role>Study Director</role>
    <affiliation>Gan and Lee Pharmaceuticals, USA Corp</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>USA002</name>
      <address>
        <city>Lafayette</city>
        <state>Indiana</state>
        <zip>47905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USA005</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USA001</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USA004</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>June 19, 2020</study_first_submitted>
  <study_first_submitted_qc>June 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 23, 2020</study_first_posted>
  <last_update_submitted>December 21, 2022</last_update_submitted>
  <last_update_submitted_qc>December 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 23, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-small Cell Lung Cancer</keyword>
  <keyword>Glioblastoma Multiforme</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>Advanced Solid Tumors</keyword>
  <keyword>GLR2007</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Glioblastoma</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/NCT04444427
org study id: GLP-CDK-1009
nct id: NCT04444427
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Evaluation of GLR2007 for Advanced Solid Tumors
An Open-Label, Multicenter, Phase 1b/2 Study to Establish Safety, Tolerability, and Optimal
      Dosing Strategy of GLR2007 in Subjects with Advanced Solid Tumors
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Part 1 employs a dose-escalation design to determine the recommended phase 2 dose. This is followed by Part 2, which involves parallel dosing of 3 different cohorts at the dose determined in Part 1.
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Escalation: Dose-limiting Toxicities
time frame: Up to 12 Months
measure: Dose Escalation: Incidence And Severity Of Adverse Events, Including The Incidence Of Dose-limiting Toxicities Within The First Cycle
time frame: Up to 12 Months
measure: Dose Expansion: Incidence And Severity Of Adverse Events
time frame: Up to 96 Weeks
measure: Dose Escalation: Objective Response Rate
time frame: 8 Weeks
description: Defined by response evaluation criteria in solid tumors (RECIST) Version 1.1 (solid tumors) or by response assessment in neuro-oncology (RANO) (brain metastases and GBM).
measure: Dose Expansion: Objective Response Rate
time frame: 12, 24, 36, 48, 60, 72, 84, and 96 Weeks
description: Defined by RECIST Version 1.1 or by RANO as appropriate.
measure: Dose Escalation And Expansion: Maximum Observed Plasma Concentration After Single And Multiple Oral Dose Administrations
time frame: 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Dose Escalation And Expansion: Time At Which Maximum Plasma Concentration Is Observed And Apparent Half-life After Single And Multiple Oral Dose Administrations
time frame: 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Dose Escalation And Expansion: Area Under The Plasma Concentration-time Curve From 0 To Last Measurable Concentration And From 0 To Infinity After Single And Multiple Oral Dose Administrations
time frame: 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Dose Escalation And Expansion: Accumulation Ratio After Single And Multiple Oral Dose Administrations
time frame: 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Dose Escalation And Expansion: Steady-state Volume Of Distribution After Single And Multiple Oral Dose Administrations
time frame: 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose
measure: Dose Escalation And Expansion: Clearance After Single And Multiple Oral Dose Administrations
time frame: 0, 0.25, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose
arm group label: Part 1: Dose Escalation
arm group type: Experimental
description: Dose escalation cohorts are planned to determine the maximum tolerated dose or recommended phase 2 dose of GLR-2007, as well as expansion cohorts and a Phase 2 cohort.
arm group label: Part 2: Dose Expansion - Cohort A
arm group type: Experimental
description: Participants who have received 2 or more second-line therapies, with at least 1 line of standard therapy, for their non-small cell lung cancer (NSCLC) will be dosed the maximal tolerated dose of GLR2007 as determined in Part 1 until lack of tolerance or disease progression.
arm group label: Part 2: Dose Expansion - Cohort B
arm group type: Experimental
description: Participants who have received 2 or more second-line therapies, with at least 1 line of standard therapy, for their brain metastases of breast or NSCLC origin will be dosed the maximal tolerated dose of GLR2007 as determined in Part 1 until lack of tolerance or disease progression.
arm group label: Part 2: Dose Expansion - Cohort C
arm group type: Experimental
description: Participants experiencing their first recurrence glioblastoma multiforme (GBM) will be dosed the maximal tolerated dose of GLR2007 as determined in Part 1 until lack of tolerance or disease progression.
intervention type: Drug
intervention name: GLR2007
description: Administered orally, once daily for 21 days followed by a 7-day treatment holiday.
arm group label: Part 1: Dose Escalation
arm group label: Part 2: Dose Expansion - Cohort A
arm group label: Part 2: Dose Expansion - Cohort B
arm group label: Part 2: Dose Expansion - Cohort C
other name: GLR2007-237FA
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Kimberly Lazaroff, MSN
role: Study Director
affiliation: Gan and Lee Pharmaceuticals, USA Corp
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Glioblastoma
sharing ipd: No