<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/NCT01723020</url>
  </required_header>
  <id_info>
    <org_study_id>20120106</org_study_id>
    <nct_id>NCT01723020</nct_id>
  </id_info>
  <brief_title>A Phase 1 Study Evaluating AMG 232 in Advanced Solid Tumors or Multiple Myeloma</brief_title>
  <official_title>A Phase 1 First-in-Human Study Evaluating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 232 in Adult Subjects With Advanced Solid Tumors or Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kartos Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kartos Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      First in human, open-label, sequential dose escalation and expansion study of AMG 232 in&#xD;
      subjects with advanced solid tumors or multiple myeloma&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study Design: This is an open-label, dose exploration study evaluating AMG 232 in subjects&#xD;
      with advanced p53WT solid tumors or multiple myeloma. The study will be conducted in 2 parts:&#xD;
      Part 1 - Dose Exploration (parts 1a, 1b and 1c) and Part 2 - Dose Expansion. Part 1a is aimed&#xD;
      at evaluating the safety, tolerability, PK and PD of AMG 232 and determining the MTD of a&#xD;
      7-day once daily (QD) dosing schedule in subjects with advanced solid tumors using a&#xD;
      practical continuous reassessment method (CRM). Part 1b will evaluate the safety and&#xD;
      tolerability of 3-day QD dosing schedule (or alternate dosing schedule based upon emerging&#xD;
      data) with a particular emphasis on evaluating the tolerability of daily doses equal to or&#xD;
      higher than the part 1a MTD in subjects with solid tumors or multiple myeloma. Part 1c will&#xD;
      evaluate the safety and tolerability of 7-day twice daily (BID) dosing schedule with daily&#xD;
      cumulative doses equal to or higher than the part 1a MTD in subjects with solid tumors. The&#xD;
      dose expansion part of the study (Part 2) can open once the MTD has been determined in Part&#xD;
      1a. Part 2, part 1b and part 1c can be explored in parallel. The dose expansion part will&#xD;
      consist of up to 85 additional subjects with specific tumors harboring MDM2 amplification&#xD;
      (liposarcoma [LPS], gliobastoma [ GBM ] and all other solid tumors) or potentially harboring&#xD;
      MDM2 overexpression (ER+ metastatic breast cancer) and a group of subjects with multiple&#xD;
      myeloma.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 27, 2012</start_date>
  <completion_date type="Actual">September 25, 2017</completion_date>
  <primary_completion_date type="Actual">March 15, 2017</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>Safety of AMG 232</measure>
    <time_frame>36 months</time_frame>
    <description>Subject incidence of adverse events, dose limiting toxicities, and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Tumor Response</measure>
    <time_frame>36 months</time_frame>
    <description>Duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, for multiple myeloma using IMWG response criteria</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Advanced Malignancy</condition>
  <condition>Advanced Solid Tumors</condition>
  <condition>Cancer</condition>
  <condition>Oncology</condition>
  <condition>Oncology Patients</condition>
  <condition>Tumors</condition>
  <condition>Glioblastoma</condition>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>AMG 232</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AMG 232 is an anti-cancer agent.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AMG 232</intervention_name>
    <description>Given an an oral tablet in escalating doses.</description>
    <arm_group_label>AMG 232</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women &gt; 18 years old&#xD;
&#xD;
          -  Pathologically documented, definitively diagnosed, advanced solid tumor that is&#xD;
             refractory to standard treatment, or which no standard therapy is available, or the&#xD;
             subject refuses standard therapy or multiple myeloma&#xD;
&#xD;
          -  Willing to undergo pre-dose core needle tumor biopsies or bone marrow aspirate for&#xD;
             subjects with multiple myeloma.&#xD;
&#xD;
          -  Ability to take oral medications and willing to record daily adherance to&#xD;
             investigational product&#xD;
&#xD;
          -  Adequate hematological, renal, hepatic, and coagulation laboratory assessments&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active brain metastases&#xD;
&#xD;
          -  For solid tumor-History or presence of hematological malignancies unless curatively&#xD;
             treated with no evidence of disease for greater than or equal to 5 years&#xD;
&#xD;
          -  Active infection requiring intravenous (IV) antibiotics&#xD;
&#xD;
          -  Anti-tumor therapy&#xD;
&#xD;
          -  Therapeutic or palliative radiation therapy within 30 days of starting treatment&#xD;
&#xD;
          -  Currently enrolled in another investigational device or drug study&#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>MD</last_name>
    <role>Study Director</role>
    <affiliation>Amgen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Norwalk</city>
        <state>Connecticut</state>
        <zip>06856</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Greenville Hospital System</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lyon CEDEX 08</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Amsterdam</city>
        <zip>1066 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rotterdam</city>
        <zip>3015 CE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
    <country>Netherlands</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.amgentrials.com</url>
    <description>AmgenTrials clinical trials website</description>
  </link>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>November 5, 2012</study_first_submitted>
  <study_first_submitted_qc>November 6, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 7, 2012</study_first_posted>
  <last_update_submitted>August 30, 2021</last_update_submitted>
  <last_update_submitted_qc>August 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid Tumors</keyword>
  <keyword>Multiple Myeloma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
    <mesh_term>Glioblastoma</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/NCT01723020
org study id: 20120106
nct id: NCT01723020
lead sponsor: 
has dmc: No
First in human, open-label, sequential dose escalation and expansion study of AMG 232 in
      subjects with advanced solid tumors or multiple myeloma
Study Design: This is an open-label, dose exploration study evaluating AMG 232 in subjects
      with advanced p53WT solid tumors or multiple myeloma. The study will be conducted in 2 parts:
      Part 1 - Dose Exploration (parts 1a, 1b and 1c) and Part 2 - Dose Expansion. Part 1a is aimed
      at evaluating the safety, tolerability, PK and PD of AMG 232 and determining the MTD of a
      7-day once daily (QD) dosing schedule in subjects with advanced solid tumors using a
      practical continuous reassessment method (CRM). Part 1b will evaluate the safety and
      tolerability of 3-day QD dosing schedule (or alternate dosing schedule based upon emerging
      data) with a particular emphasis on evaluating the tolerability of daily doses equal to or
      higher than the part 1a MTD in subjects with solid tumors or multiple myeloma. Part 1c will
      evaluate the safety and tolerability of 7-day twice daily (BID) dosing schedule with daily
      cumulative doses equal to or higher than the part 1a MTD in subjects with solid tumors. The
      dose expansion part of the study (Part 2) can open once the MTD has been determined in Part
      1a. Part 2, part 1b and part 1c can be explored in parallel. The dose expansion part will
      consist of up to 85 additional subjects with specific tumors harboring MDM2 amplification
      (liposarcoma [LPS], gliobastoma [ GBM ] and all other solid tumors) or potentially harboring
      MDM2 overexpression (ER+ metastatic breast cancer) and a group of subjects with multiple
      myeloma.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of AMG 232
time frame: 36 months
description: Subject incidence of adverse events, dose limiting toxicities, and clinically significant changes in vital signs, weight, ECGs and clinical laboratory tests
measure: Objective Tumor Response
time frame: 36 months
description: Duration of overall response and duration of stable disease measured by CT or MRI and assessed per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, for multiple myeloma using IMWG response criteria
arm group label: AMG 232
arm group type: Experimental
description: AMG 232 is an anti-cancer agent.
intervention type: Drug
intervention name: AMG 232
description: Given an an oral tablet in escalating doses.
arm group label: AMG 232
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: MD
role: Study Director
affiliation: Amgen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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country: France
country: Netherlands
country: United States
url: http://www.amgentrials.com
description: AmgenTrials clinical trials website
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Glioblastoma