<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/NCT03006029</url>
  </required_header>
  <id_info>
    <org_study_id>TAB08-ONC-01</org_study_id>
    <nct_id>NCT03006029</nct_id>
  </id_info>
  <brief_title>Dose Escalation Study of TAB08 in Patients With Advanced Solid Neoplasms</brief_title>
  <acronym>TAB08</acronym>
  <official_title>A Phase 1b Multiple Dose Escalation Study of TAB08 in Patients With Advanced Solid Neoplasms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Theramab LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Theramab LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended&#xD;
      Phase 2 dose of TAB08 when administered intravenously (i.v.) to patients with advanced solid&#xD;
      malignancies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, multi-center, sequential groups, dose escalation study of TAB08 in&#xD;
      patients with metastatic or unresectable advanced solid malignancies. The study will consist&#xD;
      of 2 parts: a dose-escalation part with a standard &quot;3+3&quot; design, followed by a dose-expansion&#xD;
      part once the maximum tolerated dose (MTD) has been determined.&#xD;
&#xD;
      Patients must have documented recurrent or refractory solid tumors; patients enrolled in the&#xD;
      dose-expansion part of the trial must have least one lesion that may qualify as a target&#xD;
      lesion based on the RECIST 1.1 criteria. Following the provision of signed informed consent,&#xD;
      patients will be screened for entry into the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2017</start_date>
  <completion_date type="Actual">August 13, 2019</completion_date>
  <primary_completion_date type="Actual">May 14, 2019</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of cases of the Dose-limiting toxicity (DLT)</measure>
    <time_frame>DLT assessment will be performed within first 2 weeks of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events (including local reactions) frequency, seriousness and severity</measure>
    <time_frame>Through study completion, not less than 8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TAB08 concentrations in peripheral blood</measure>
    <time_frame>First 4 weeks of TAB08 administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response to TAB08 according to immune-related Response Criteria in Solid Tumors (irRECIST)</measure>
    <time_frame>Through study completion, not less than 12 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of T-lymphocytes subsets in absolute count (number of cells per mL) in peripheral blood at designated timepoints comparing to Baseline.</measure>
    <time_frame>Through study completion, not less than 8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of T-lymphocytes subsets in percent in peripheral blood at designated timepoints comparing to Baseline.</measure>
    <time_frame>Through study completion, not less than 8 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of cytokines concentrations (in micrograms/mL) in peripheral blood at designated timepoints comparing to Baseline.</measure>
    <time_frame>Through study completion, not less than 8 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Solid Tumors</condition>
  <arm_group>
    <arm_group_label>TAB08( Theralizumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TAB08 will be administered i.v. over 1 hour weekly for 3 weeks followed by 3 weeks of no treatment; with 6 weeks interval between start of each treatment cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAB08</intervention_name>
    <description>The initial dose of TAB08 will be 1 µg/kg TAB08 will be administered i.v. over 1 hour weekly for 3 weeks followed by 3 weeks of no treatment; with 6 weeks interval between start of each treatment cycle.</description>
    <arm_group_label>TAB08( Theralizumab)</arm_group_label>
    <other_name>Theralizumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subjects or their authorized representatives must be able to provide written informed&#xD;
             consent.&#xD;
&#xD;
          2. Subjects must have histological or cytological evidence of a solid neoplasm for which&#xD;
             standard therapy has failed or does not exist or is not available for patient due to&#xD;
             any reason.&#xD;
&#xD;
          3. Subjects enrolled in the expansion cohort must have at least one measurable evaluable&#xD;
             lesion.&#xD;
&#xD;
          4. Subjects must have ECOG (Eastern Cooperation Oncology Group) performance status of 0&#xD;
             or 1.&#xD;
&#xD;
          5. Subjects must be ≥ 18 years of age.&#xD;
&#xD;
          6. Subjects must have adequate organ function, as defined by the following criteria:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) &gt; 1,500/µL.&#xD;
&#xD;
               -  Platelet count &gt; 75,000/µL.&#xD;
&#xD;
               -  Hemoglobin (Hb) &gt; 8.0 g/dL.&#xD;
&#xD;
               -  Serum creatinine of &lt; 1.5 x upper limit of normal (ULN) or a calculated&#xD;
                  Glomerular Filtration Rate of &gt;40 mL/min/1.73m2.&#xD;
&#xD;
               -  Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x&#xD;
                  ULN (&lt; 5 x ULN for subjects with known liver metastases).&#xD;
&#xD;
          7. At least 2 weeks or at least 5 half-lives must have elapsed since prior treatment with&#xD;
             chemotherapy, targeted therapy, radiotherapy, immunotherapy, or investigational&#xD;
             anti-cancer therapy prior to study drug administration. The maximum washout period&#xD;
             will not exceed 4 weeks. .&#xD;
&#xD;
          8. Subjects must have recovered from the effects of any prior surgery, radiotherapy,&#xD;
             localized therapy, or systemic therapy to Grade 1 or lower (except alopecia or anemia&#xD;
             - Grade 2 permitted).&#xD;
&#xD;
          9. Subjects have a life expectancy ≥ 3 months at study entry.&#xD;
&#xD;
         10. Women of childbearing potential and men with partners of childbearing potential must&#xD;
             agree to abstain from sexual intercourse or use an effective form of contraception.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with an uncontrolled concurrent illness, including, but not limited to the&#xD;
             following: ongoing active infection requiring systemic treatment; uncontrolled&#xD;
             endocrine disease; diabetes mellitus or chronic obstructive pulmonary disease (COPD)&#xD;
             requiring hospitalization within the preceding 6 months.&#xD;
&#xD;
          2. Subjects with uncontrolled arterial hypertension, heart failure by New York Heart&#xD;
             Association (NYHA) Class 3 or 4, left ventricular ejection fraction (LVEF) &lt; 50% by&#xD;
             echocardiography, myocardial infarction, acute coronary syndrome and/or QT&#xD;
             prolongations within the preceding 6 months or history of cerebrovascular accidents&#xD;
             including episodes of transient ischemic attacks.&#xD;
&#xD;
          3. Subjects with altered mental status or psychiatric illness or social circumstances&#xD;
             that would limit compliance with the study requirements and/or obscure the results.&#xD;
&#xD;
          4. Immunocompromised subjects, e.g., subjects known to be infected with human&#xD;
             immunodeficiency virus (HIV) by medical history, and subjects with active hepatitis A,&#xD;
             B, or C by medical history.&#xD;
&#xD;
          5. Subjects having untreated or symptomatic brain metastasis, or subjects with&#xD;
             leptomeningeal disease. (Subjects with treated metastases, who are off corticosteroids&#xD;
             and who are neurologically stable for at least 2 months may participate in the trial.)&#xD;
&#xD;
          6. A history of major surgery within 28 days prior to the first dose of study drug.&#xD;
&#xD;
          7. Subjects with history of other malignancies within the preceding 5 years (except for&#xD;
             subjects with non-melanoma skin cancers, cervical intra-epithelial neoplasia, prostate&#xD;
             cancer Gleason ≤ 6 and Prostate Specific Antigen (PSA) &lt; 10 ng/mL, radically excised&#xD;
             lobular breast carcinoma in situ or ductal breast carcinoma in situ ≤ 15 mm) unless&#xD;
             they have undergone potentially curative therapy and have had no evidence of disease&#xD;
             for 3 years (ie, 5 years since diagnosis, no treatment or symptoms of disease for the&#xD;
             last 3 years).&#xD;
&#xD;
          8. Women who are pregnant or nursing.&#xD;
&#xD;
          9. Subjects with any other disease, metabolic dysfunction, physical examination finding,&#xD;
             or clinical laboratory finding that, in the opinion of the investigator,&#xD;
             contraindicates use of the investigational drug, or may render the subject as&#xD;
             excessively high risk for treatment complications.&#xD;
&#xD;
         10. Subjects with any other condition as determined by medical history, including&#xD;
             substance abuse that, in the opinion of the investigator, would render the subject&#xD;
             unable to cooperate in the trial or place the subject at undue risk.&#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>Daniil G Nemenov, MD</last_name>
    <role>Study Director</role>
    <affiliation>Theramab LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GBU Ryazanskoy Oblasti &quot;Oblastnoy klinicheckiy oncologicheskiy dispanser&quot;</name>
      <address>
        <city>Ryazan'</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 29, 2016</study_first_submitted>
  <study_first_submitted_qc>December 26, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 30, 2016</study_first_posted>
  <last_update_submitted>October 5, 2021</last_update_submitted>
  <last_update_submitted_qc>October 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</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/NCT03006029
org study id: TAB08-ONC-01
nct id: NCT03006029
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to determine the maximum tolerated dose (MTD) and recommended
      Phase 2 dose of TAB08 when administered intravenously (i.v.) to patients with advanced solid
      malignancies.
This is an open-label, multi-center, sequential groups, dose escalation study of TAB08 in
      patients with metastatic or unresectable advanced solid malignancies. The study will consist
      of 2 parts: a dose-escalation part with a standard "3+3" design, followed by a dose-expansion
      part once the maximum tolerated dose (MTD) has been determined.

      Patients must have documented recurrent or refractory solid tumors; patients enrolled in the
      dose-expansion part of the trial must have least one lesion that may qualify as a target
      lesion based on the RECIST 1.1 criteria. Following the provision of signed informed consent,
      patients will be screened for entry into the study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Number of cases of the Dose-limiting toxicity (DLT)
time frame: DLT assessment will be performed within first 2 weeks of treatment
measure: Adverse events (including local reactions) frequency, seriousness and severity
time frame: Through study completion, not less than 8 weeks
measure: TAB08 concentrations in peripheral blood
time frame: First 4 weeks of TAB08 administration
measure: Tumor response to TAB08 according to immune-related Response Criteria in Solid Tumors (irRECIST)
time frame: Through study completion, not less than 12 weeks
measure: Change of T-lymphocytes subsets in absolute count (number of cells per mL) in peripheral blood at designated timepoints comparing to Baseline.
time frame: Through study completion, not less than 8 weeks
measure: Change of T-lymphocytes subsets in percent in peripheral blood at designated timepoints comparing to Baseline.
time frame: Through study completion, not less than 8 weeks
measure: Change of cytokines concentrations (in micrograms/mL) in peripheral blood at designated timepoints comparing to Baseline.
time frame: Through study completion, not less than 8 weeks
arm group label: TAB08( Theralizumab)
arm group type: Experimental
description: TAB08 will be administered i.v. over 1 hour weekly for 3 weeks followed by 3 weeks of no treatment; with 6 weeks interval between start of each treatment cycle.
intervention type: Drug
intervention name: TAB08
description: The initial dose of TAB08 will be 1 µg/kg TAB08 will be administered i.v. over 1 hour weekly for 3 weeks followed by 3 weeks of no treatment; with 6 weeks interval between start of each treatment cycle.
arm group label: TAB08( Theralizumab)
other name: Theralizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Daniil G Nemenov, MD
role: Study Director
affiliation: Theramab LLC
facility: 
country: Russian Federation
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No