<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/NCT02978235</url>
  </required_header>
  <id_info>
    <org_study_id>TAS-4464-101</org_study_id>
    <nct_id>NCT02978235</nct_id>
  </id_info>
  <brief_title>A Dose Finding Study Followed by a Safety and Efficacy Study for Patients With Multiple Myeloma or Lymphoma</brief_title>
  <official_title>A Phase 1, Open-Label Safety, Pharmacokinetic and Efficacy Study of TAS4464 in Patients With Multiple Myeloma or Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Taiho Oncology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Taiho Oncology, Inc.</source>
  <oversight_info>
    <has_dmc>No</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>
      The Phase 1 portion of this study will determine the safety of TAS4464 and the most&#xD;
      appropriate dose for patients with Multiple Myeloma or Lymphoma.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The trial was put on Clinical Hold prior to Phase 2 due to cases of drug induced liver injury&#xD;
      meeting the criteria for Hy's Law.&#xD;
&#xD;
      Background and Rationale:&#xD;
&#xD;
      • TAS4464 is an investigational NEDD8 activating enzyme (NAE) inhibitor, a compound which may&#xD;
      affect cancer cell growth and survival. Thus, TAS4464 may help in the treatment of cancer.&#xD;
&#xD;
      Phase 1:&#xD;
&#xD;
      Primary:&#xD;
&#xD;
        -  To investigate the safety and tolerability of TAS4464&#xD;
&#xD;
        -  To identify a tolerated dose of TAS4464&#xD;
&#xD;
      Secondary:&#xD;
&#xD;
        -  To investigate the preliminary efficacy of TAS4464&#xD;
&#xD;
        -  To investigate the pharmacokinetics (PK) and the pharmacogenomics (PGx) of TAS4464&#xD;
&#xD;
        -  To investigate the pharmacodynamics of TAS4464&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The trial was put on Clinical Hold and subsequently terminated prior to Phase 2 due to cases of&#xD;
    drug induced liver injury meeting the criteria for Hy's Law&#xD;
  </why_stopped>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">February 1, 2018</completion_date>
  <primary_completion_date type="Actual">February 1, 2018</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>Number of patients experiencing any dose-limiting toxicities, during dose escalation period, to determine maximum tolerated dose of TAS4464, using NCI CTCAE criteria, laboratory testing, performance status assessments, and other routine visit procedures</measure>
    <time_frame>Completion of Cycle 1 (28 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Efficacy of TAS4464, defined as Objective Response Rate (ORR) per IWG criteria (NHL) and IMWG criteria (MM). This will take into consideration routine assessments including: imaging scans, physical exams, blood tests, urine tests and biopsy results</measure>
    <time_frame>Up to 5 years</time_frame>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Multiple Myeloma</condition>
  <condition>NonHodgkin Lymphoma</condition>
  <arm_group>
    <arm_group_label>TAS4464</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TAS4464</intervention_name>
    <description>Intravenous (IV) Infusion</description>
    <arm_group_label>TAS4464</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provide written informed consent&#xD;
&#xD;
          2. Women of child-bearing potential must have a negative pregnancy test&#xD;
&#xD;
        Multiple Myeloma:&#xD;
&#xD;
        Confirmed diagnosis of Multiple Myeloma with measurable disease, having been treated with&#xD;
        at least two prior lines of therapy.&#xD;
&#xD;
        Lymphoma:&#xD;
&#xD;
        Confirmed diagnosis of Non-Hodgkin Lymphoma with measurable disease, having been treated&#xD;
        with at least one anthracycline-based therapy, with relapse or progression since the last&#xD;
        treatment received.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any of the following treatments, within the specified time frame, prior to the first&#xD;
             dose of TAS4464:&#xD;
&#xD;
               1. Major surgery within 28 days&#xD;
&#xD;
               2. Radiation/chemotherapy within 21 days&#xD;
&#xD;
               3. Monoclonal antibodies within 28 days&#xD;
&#xD;
               4. Corticosteroid administration &gt;20 mg/day of prednisone or equivalent within 14&#xD;
                  days&#xD;
&#xD;
               5. Proteasome inhibitors within 14 days&#xD;
&#xD;
               6. Immunomodulatory agents within 7 days&#xD;
&#xD;
               7. Stem cell transplant within 3 months&#xD;
&#xD;
               8. Current immunosuppressive treatment for graft versus host disease&#xD;
&#xD;
               9. Current use of an investigational agent&#xD;
&#xD;
          2. Active graft versus host disease&#xD;
&#xD;
          3. Known serious illness or medical condition&#xD;
&#xD;
          4. Prior treatment with TAS4464 or known hypersensitivity to any of its inactive&#xD;
             ingredients or drugs similar in class&#xD;
&#xD;
          5. Pregnant or breast-feeding female&#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>Center for Cancer and Blood Disorders</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Weisberg Cancer Treatment Center</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Theurer Cancer Center at Hackensack Meridian Health</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 30, 2016</study_first_posted>
  <last_update_submitted>June 18, 2021</last_update_submitted>
  <last_update_submitted_qc>June 18, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Relapsed/Refractory</keyword>
  <keyword>Lymphoma</keyword>
  <keyword>Non-Hodgkin Lymphoma</keyword>
  <keyword>Diffuse Large B-Cell Lymphoma</keyword>
  <keyword>DLBCL</keyword>
  <keyword>Mantle Cell Lymphoma</keyword>
  <keyword>MCL</keyword>
  <keyword>Peripheral T-Cell Lymphoma</keyword>
  <keyword>PTCL</keyword>
  <keyword>TAS4464</keyword>
  <keyword>NEDD8</keyword>
  <keyword>NAE inhibitor</keyword>
  <keyword>Neoplasms</keyword>
  <keyword>Hematologic Diseases</keyword>
  <keyword>Myeloma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</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/NCT02978235
org study id: TAS-4464-101
nct id: NCT02978235
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The Phase 1 portion of this study will determine the safety of TAS4464 and the most
      appropriate dose for patients with Multiple Myeloma or Lymphoma.
The trial was put on Clinical Hold prior to Phase 2 due to cases of drug induced liver injury
      meeting the criteria for Hy's Law.

      Background and Rationale:

      • TAS4464 is an investigational NEDD8 activating enzyme (NAE) inhibitor, a compound which may
      affect cancer cell growth and survival. Thus, TAS4464 may help in the treatment of cancer.

      Phase 1:

      Primary:

        -  To investigate the safety and tolerability of TAS4464

        -  To identify a tolerated dose of TAS4464

      Secondary:

        -  To investigate the preliminary efficacy of TAS4464

        -  To investigate the pharmacokinetics (PK) and the pharmacogenomics (PGx) of TAS4464

        -  To investigate the pharmacodynamics of TAS4464
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of patients experiencing any dose-limiting toxicities, during dose escalation period, to determine maximum tolerated dose of TAS4464, using NCI CTCAE criteria, laboratory testing, performance status assessments, and other routine visit procedures
time frame: Completion of Cycle 1 (28 days)
measure: Efficacy of TAS4464, defined as Objective Response Rate (ORR) per IWG criteria (NHL) and IMWG criteria (MM). This will take into consideration routine assessments including: imaging scans, physical exams, blood tests, urine tests and biopsy results
time frame: Up to 5 years
arm group label: TAS4464
arm group type: Experimental
intervention type: Drug
intervention name: TAS4464
description: Intravenous (IV) Infusion
arm group label: TAS4464
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Lymphoma, Non-Hodgkin