<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/NCT04430842</url>
  </required_header>
  <id_info>
    <org_study_id>QBS-72S-1001</org_study_id>
    <nct_id>NCT04430842</nct_id>
  </id_info>
  <brief_title>Dose Escalation Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S</brief_title>
  <official_title>A Phase 1, Open Label, Multi-Center, Single and Multiple Dose, Dose Escalation and Expansion Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of QBS10072S in Previously Treated Patients With Advanced or Metastatic Cancers With High LAT1 Signatures, and in Patients With Relapsed or Refractory Grade 4 Astrocytoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Quadriga Biosciences, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Novotech (Australia) Pty Limited</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Quadriga Biosciences, Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, open-label, dose escalation study to determine the safety,&#xD;
      tolerability, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of&#xD;
      QBS10072S in patients with advanced or metastatic cancers with high LAT1 expression. The MTD&#xD;
      of QBS10072S will be confirmed in patients with relapsed or refractory grade 4 astrocytoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Actual">December 22, 2022</completion_date>
  <primary_completion_date type="Actual">September 21, 2022</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>Sequential Assignment</intervention_model>
    <intervention_model_description>The dose escalation scheme for this trial employs an mTPI-2 design.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Determination of maximum tolerated dose (MTD)</measure>
    <time_frame>28 days</time_frame>
    <description>MTD will be determined by presence of AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability assessed by adverse events and serious adverse events</measure>
    <time_frame>28 days</time_frame>
    <description>Safety and tolerability will be determined by adverse events as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax)</measure>
    <time_frame>28 days</time_frame>
    <description>Determine the maximum plasma concentration of QBS10072S.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC) of QBS10072S</measure>
    <time_frame>28 days</time_frame>
    <description>Determine the plasma concentration of QBS10072S over time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of QBS10072S in plasma (t1/2)</measure>
    <time_frame>28 days</time_frame>
    <description>Determine the half life of QBS10072S in plasma; the half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum concentration of QBS10072S in plasma (Tmax)</measure>
    <time_frame>28 days</time_frame>
    <description>Determine the time it takes to achieve maximum concentration of QBS10072S in plasma.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Astrocytoma</condition>
  <condition>Brain Cancer</condition>
  <condition>Brain Metastases</condition>
  <condition>Bladder Cancer</condition>
  <condition>Breast Cancer</condition>
  <condition>Cervical Cancer</condition>
  <condition>Cholangiocarcinoma</condition>
  <condition>Colorectal Cancer</condition>
  <condition>Esophagus Cancer</condition>
  <condition>Gastric Cancer</condition>
  <condition>Head and Neck Cancer</condition>
  <condition>Kidney Cancer</condition>
  <condition>Liver Cancer</condition>
  <condition>Lung Cancer</condition>
  <condition>Melanoma</condition>
  <condition>Ovarian Cancer</condition>
  <condition>Pancreatic Cancer</condition>
  <condition>Pleural Mesothelioma</condition>
  <condition>Prostate Cancer</condition>
  <condition>Sarcoma</condition>
  <condition>Tongue Cancer</condition>
  <condition>Thymic Carcinoma</condition>
  <condition>Urinary Tract Cancer</condition>
  <arm_group>
    <arm_group_label>Dose escalation of QBS10072S</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous administration of QBS10072S once every 4 weeks starting at 3mg/m2 and increasing dose levels in subsequent cohorts.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QBS10072S</intervention_name>
    <description>QBS10072S targets cancers with high LAT1 expression.</description>
    <arm_group_label>Dose escalation of QBS10072S</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female participants aged ≥18 years at the time of informed consent.&#xD;
&#xD;
          2. Adequate Bone Marrow Function&#xD;
&#xD;
          3. Adequate renal function&#xD;
&#xD;
          4. Adequate Liver Function&#xD;
&#xD;
          5. Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade ≤1&#xD;
             except for AEs not constituting a safety risk by Investigator judgment.&#xD;
&#xD;
          6. A histological or cytological diagnosis of a solid tumor that is advanced/metastatic,&#xD;
             patients intolerant to standard treatment or, resistant to standard therapy* (per NCCN&#xD;
             guidelines) or for which no curative therapy is available for the following tumor&#xD;
             types:&#xD;
&#xD;
             - Bladder, Brain, Breast, Cervical, Cholangiocarcinoma, Colorectal, Esophageal,&#xD;
             Gastric, Head and Neck, Kidney, Liver, Lung, Melanoma, Ovarian, Pancreatic, Pleural&#xD;
             mesothelioma, Prostate, Sarcoma, Tongue cancer, Thymic carcinomas, Urinary tract&#xD;
&#xD;
          7. At least one measurable lesion (as defined by RECIST version 1.1) that has not been&#xD;
             previously irradiated.&#xD;
&#xD;
          8. An ECOG PS 0 to 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with tumor primarily localized to the brainstem or spinal cord. Presence of&#xD;
             known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or&#xD;
             leptomeningeal disease as indicated by clinical symptoms, cerebral edema, and/or&#xD;
             progressive growth.&#xD;
&#xD;
          2. Patients with advanced/metastatic, symptomatic, visceral spread, that are at risk of&#xD;
             life-threatening complications in the short term (including patients with massive&#xD;
             uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and&#xD;
             over 50% liver involvement).&#xD;
&#xD;
          3. Patients with any other active malignancy within 3 years prior to enrollment, except&#xD;
             for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ.&#xD;
&#xD;
          4. Major surgery within 4 weeks prior to study entry.&#xD;
&#xD;
          5. Radiation therapy within 4 weeks prior to receiving the first QBS10072S dose (bone&#xD;
             lesions requiring radiation may be treated with limited radiation therapy during this&#xD;
             period).&#xD;
&#xD;
          6. Systemic anticancer therapy within 4 weeks prior to study entry&#xD;
&#xD;
          7. Bleeding esophageal or gastric varices &lt;2 months prior to the date of informed&#xD;
             consent.&#xD;
&#xD;
          8. Unmanageable ascites.&#xD;
&#xD;
          9. Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may&#xD;
             affect patient safety or interpretation of study results&#xD;
&#xD;
         10. On therapeutic anticoagulation, except low molecular weight heparin, vitamin K&#xD;
             antagonists or factor Xa inhibitors may be allowed following discussion with the&#xD;
             Sponsor.&#xD;
&#xD;
         11. Any of the following in the previous 6 months: myocardial infarction, congenital long&#xD;
             QT syndrome, Torsade de Pointes, clinically significant arrhythmias (including&#xD;
             sustained ventricular tachyarrhythmia and ventricular fibrillation), left anterior&#xD;
             hemiblock, bifascicular block, unstable angina, coronary/peripheral artery bypass&#xD;
             graft, symptomatic congestive heart failure (New York Heart Association class III or&#xD;
             IV), cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary&#xD;
             embolism or other clinical significant episode of thromboembolic disease. Ongoing&#xD;
             cardiac dysrhythmias of NCI CTCAE Grade ≥2, atrial fibrillation of any grade (Grade ≥2&#xD;
             in the case of asymptomatic lone atrial fibrillation).&#xD;
&#xD;
         12. Hypertension that cannot be controlled by medications (&gt;150/90 mmHg despite optimal&#xD;
             medical therapy) or requiring more than two medications for adequate control.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>St George Private Hospital</name>
      <address>
        <city>Kogarah</city>
        <state>New South Wales</state>
        <zip>2217</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sydney Southwest Private Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 2, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>January 16, 2023</last_update_submitted>
  <last_update_submitted_qc>January 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 18, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 1</keyword>
  <keyword>Dose escalation</keyword>
  <keyword>Metastatic</keyword>
  <keyword>Brain metastasis</keyword>
  <keyword>Brain metastases</keyword>
  <keyword>GBM</keyword>
  <keyword>Astrocytoma</keyword>
  <keyword>Brain tumor</keyword>
  <keyword>Cancer</keyword>
  <keyword>Oncology</keyword>
  <keyword>Glioblastoma</keyword>
  <keyword>Glioblastoma multiforme</keyword>
  <keyword>Brain</keyword>
  <keyword>Neurology</keyword>
  <keyword>Neuroscience</keyword>
  <keyword>Headaches</keyword>
  <keyword>Vomiting</keyword>
  <keyword>Seizures</keyword>
  <keyword>Drowsiness</keyword>
  <keyword>Chemotherapy</keyword>
  <keyword>Surgery</keyword>
  <keyword>Radiation</keyword>
  <keyword>Neuro-oncology</keyword>
  <keyword>Blurred vision</keyword>
  <keyword>Loss of appetite</keyword>
  <keyword>Speech difficulty</keyword>
  <keyword>Changes in ability to think and learn</keyword>
  <keyword>Changes in mood and personality</keyword>
  <keyword>Persistent headaches</keyword>
  <keyword>Neuropathologist</keyword>
  <keyword>Magnetic resonance spectroscopy (MRS)</keyword>
  <keyword>Positron emission tomography (PET scan)</keyword>
  <keyword>Intraoperative MRI</keyword>
  <keyword>Tumor removal</keyword>
  <keyword>Craniotomy</keyword>
  <keyword>Standard external beam radiation therapy</keyword>
  <keyword>Radiosurgery</keyword>
  <keyword>Temozolomide</keyword>
  <keyword>Bevacizumab</keyword>
  <keyword>Avastin</keyword>
  <keyword>Neurological exam</keyword>
  <keyword>TMZ</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Mesothelioma</mesh_term>
    <mesh_term>Cholangiocarcinoma</mesh_term>
    <mesh_term>Astrocytoma</mesh_term>
    <mesh_term>Esophageal Neoplasms</mesh_term>
    <mesh_term>Thymoma</mesh_term>
    <mesh_term>Tongue Neoplasms</mesh_term>
    <mesh_term>Urologic 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/NCT04430842
org study id: QBS-72S-1001
nct id: NCT04430842
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This is a multi-center, open-label, dose escalation study to determine the safety,
      tolerability, pharmacokinetics, pharmacodynamics, and maximum tolerated dose (MTD) of
      QBS10072S in patients with advanced or metastatic cancers with high LAT1 expression. The MTD
      of QBS10072S will be confirmed in patients with relapsed or refractory grade 4 astrocytoma.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: The dose escalation scheme for this trial employs an mTPI-2 design.
primary purpose: Treatment
masking: None (Open Label)
measure: Determination of maximum tolerated dose (MTD)
time frame: 28 days
description: MTD will be determined by presence of AEs as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
measure: Safety and tolerability assessed by adverse events and serious adverse events
time frame: 28 days
description: Safety and tolerability will be determined by adverse events as characterized by type, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy.
measure: Peak Plasma Concentration (Cmax)
time frame: 28 days
description: Determine the maximum plasma concentration of QBS10072S.
measure: Area under the plasma concentration versus time curve (AUC) of QBS10072S
time frame: 28 days
description: Determine the plasma concentration of QBS10072S over time.
measure: Half-life of QBS10072S in plasma (t1/2)
time frame: 28 days
description: Determine the half life of QBS10072S in plasma; the half-life of a drug is the time taken for the plasma concentration of a drug to reduce to half its original value.
measure: Time to maximum concentration of QBS10072S in plasma (Tmax)
time frame: 28 days
description: Determine the time it takes to achieve maximum concentration of QBS10072S in plasma.
arm group label: Dose escalation of QBS10072S
arm group type: Experimental
description: Intravenous administration of QBS10072S once every 4 weeks starting at 3mg/m2 and increasing dose levels in subsequent cohorts.
intervention type: Drug
intervention name: QBS10072S
description: QBS10072S targets cancers with high LAT1 expression.
arm group label: Dose escalation of QBS10072S
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Brain Neoplasms
mesh term: Mesothelioma
mesh term: Cholangiocarcinoma
mesh term: Astrocytoma
mesh term: Esophageal Neoplasms
mesh term: Thymoma
mesh term: Tongue Neoplasms
mesh term: Urologic Neoplasms