<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/NCT02221505</url>
  </required_header>
  <id_info>
    <org_study_id>CLOP628X2101</org_study_id>
    <nct_id>NCT02221505</nct_id>
  </id_info>
  <brief_title>Phase 1 Study of LOP628 in Adult Patients With cKit-positive Solid Tumors and Acute Myeloid Leukemia</brief_title>
  <official_title>A Phase I, Multicenter, Open-label Dose Escalation and Expansion Study of LOP628, Administered Intravenously in Adult Patients With cKit-positive Tumors and Acute Myeloid Leukemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      LOP628 is an antibody-drug conjugate (ADC) consisting of an anti-cKit humanized IgG1/κ&#xD;
      antibody conjugated to a maytansine payload via a non-cleavable linker.&#xD;
&#xD;
      LOP628 provides an opportunity to target cKit overexpressing tumors.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <start_date>December 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incident rate of dose limiting toxicities (DLTs)</measure>
    <time_frame>Month 12</time_frame>
    <description>To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events (AEs) and serious adverse events (SAE)</measure>
    <time_frame>30 months</time_frame>
    <description>Characterize the safety and tolerability of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of adverse events (AEs) and serious adverse events (SAEs)</measure>
    <time_frame>30 months</time_frame>
    <description>Characterize the safety and tolerability of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum PK parameters (AUC, Cmax, Tmax, and half-life)</measure>
    <time_frame>30 months</time_frame>
    <description>To characterize the pharmacokinetic profile of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum concentration vs. time profiles</measure>
    <time_frame>30 months</time_frame>
    <description>To characterize the pharmacokinetic profile of LOP628.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR)</measure>
    <time_frame>30 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>30 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>30 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) at 4 months</measure>
    <time_frame>4 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best overall response (BOR)</measure>
    <time_frame>30 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628 in patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (AML)</measure>
    <time_frame>30 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) (AML)</measure>
    <time_frame>30 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Event Free Survival (EFS) (AML)</measure>
    <time_frame>30 months</time_frame>
    <description>To assess the preliminary anti-tumor activity of LOP628</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>cKIT-positive Solid Tumors</condition>
  <condition>AML</condition>
  <arm_group>
    <arm_group_label>LOP628 - Solid Tumor</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>with LOP628</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LOP628 - AML</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>With LOP628</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LOP628 - Solid Tumor Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>With LOP628</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LOP628</intervention_name>
    <arm_group_label>LOP628 - AML</arm_group_label>
    <arm_group_label>LOP628 - Solid Tumor</arm_group_label>
    <arm_group_label>LOP628 - Solid Tumor Expansion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        For patients with solid tumors:&#xD;
&#xD;
          -  documented cKit-positive neoplasms&#xD;
&#xD;
          -  Patient must have progressive disease as defined by any of the following:&#xD;
&#xD;
          -  SCLC: patient has progressed after at least 1 prior therapy&#xD;
&#xD;
          -  GIST : patient has relapsed or has refractory disease, and no further approved&#xD;
             effective therapeutic option exists&#xD;
&#xD;
          -  Patients with other cKit-positive solid tumors: patient has progressed after at least&#xD;
             one prior line of therapy and no further approved effective therapeutic option exists&#xD;
&#xD;
          -  Patient has measurable disease as per RECIST v1.1 criteria&#xD;
&#xD;
        For patients with AML:&#xD;
&#xD;
          -  documented cKit-positive acute myelogenous leukemia&#xD;
&#xD;
          -  Consent to newly obtained bone marrow aspirate&#xD;
&#xD;
          -  Patient must have progressive disease defined as relapsed or refractory non-PML AML&#xD;
             following standard therapy or for whom no effective therapy exists.&#xD;
&#xD;
          -  Blast count &lt; 50,000/mm3&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        For patients with solid tumors:&#xD;
&#xD;
          -  Patient has central nervous system (CNS) metastatic involvement unless the CNS&#xD;
             metastases have been previously treated and the patient is clinically stable and on a&#xD;
             stable dose of corticosteroids for at least 4 weeks prior to enrollment.&#xD;
&#xD;
          -  Patient has the presence of other clinically significant hematologic, cardiac,&#xD;
             respiratory, gastrointestinal, renal, hepatic or neurological conditions.&#xD;
&#xD;
          -  Patient has a history of serious allergic reactions, which in the opinion of the&#xD;
             investigator may pose an increased risk of serious infusion reactions&#xD;
&#xD;
          -  Patient has been previously treated with cKit directed antibodies&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
        For patients with AML:&#xD;
&#xD;
          -  Patient has received prior allogeneic bone marrow transplant (BMT).&#xD;
&#xD;
          -  Patient has the presence of other clinically significant cardiac, respiratory,&#xD;
             gastrointestinal, renal, hepatic or neurological disease&#xD;
&#xD;
          -  Patient has a history of serious allergic reactions, which in the opinion of the&#xD;
             investigator may pose an increased risk of serious infusion reactions&#xD;
&#xD;
          -  Patient has been previously treated with cKit directed antibodies&#xD;
&#xD;
          -  Pregnant or nursing women&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Leiden</city>
        <zip>2300 RC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Netherlands</country>
    <country>Spain</country>
  </location_countries>
  <removed_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>United States</country>
  </removed_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>August 19, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2014</study_first_posted>
  <last_update_submitted>April 2, 2016</last_update_submitted>
  <last_update_submitted_qc>April 2, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>LOP628,</keyword>
  <keyword>cKit,</keyword>
  <keyword>ADC,</keyword>
  <keyword>Antibody drug conjugates,</keyword>
  <keyword>maytansine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leukemia, Myeloid, Acute</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/NCT02221505
org study id: CLOP628X2101
nct id: NCT02221505
lead sponsor: 
has dmc: No
LOP628 is an antibody-drug conjugate (ADC) consisting of an anti-cKit humanized IgG1/κ
      antibody conjugated to a maytansine payload via a non-cleavable linker.

      LOP628 provides an opportunity to target cKit overexpressing tumors.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incident rate of dose limiting toxicities (DLTs)
time frame: Month 12
description: To estimate the maximum tolerated dose/recommended dose for expansion (MTD/RDE)
measure: Incidence of adverse events (AEs) and serious adverse events (SAE)
time frame: 30 months
description: Characterize the safety and tolerability of LOP628
measure: Severity of adverse events (AEs) and serious adverse events (SAEs)
time frame: 30 months
description: Characterize the safety and tolerability of LOP628
measure: Serum PK parameters (AUC, Cmax, Tmax, and half-life)
time frame: 30 months
description: To characterize the pharmacokinetic profile of LOP628
measure: Serum concentration vs. time profiles
time frame: 30 months
description: To characterize the pharmacokinetic profile of LOP628.
measure: Overall response rate (ORR)
time frame: 30 months
description: To assess the preliminary anti-tumor activity of LOP628
measure: Duration of response (DOR)
time frame: 30 months
description: To assess the preliminary anti-tumor activity of LOP628
measure: Progression Free Survival (PFS)
time frame: 30 months
description: To assess the preliminary anti-tumor activity of LOP628
measure: Disease Control Rate (DCR) at 4 months
time frame: 4 months
description: To assess the preliminary anti-tumor activity of LOP628
measure: Best overall response (BOR)
time frame: 30 months
description: To assess the preliminary anti-tumor activity of LOP628 in patients
measure: Best Overall Response (AML)
time frame: 30 months
description: To assess the preliminary anti-tumor activity of LOP628
measure: Duration of response (DOR) (AML)
time frame: 30 months
description: To assess the preliminary anti-tumor activity of LOP628
measure: Event Free Survival (EFS) (AML)
time frame: 30 months
description: To assess the preliminary anti-tumor activity of LOP628
arm group label: LOP628 - Solid Tumor
arm group type: Experimental
description: with LOP628
arm group label: LOP628 - AML
arm group type: Experimental
description: With LOP628
arm group label: LOP628 - Solid Tumor Expansion
arm group type: Experimental
description: With LOP628
intervention type: Drug
intervention name: LOP628
arm group label: LOP628 - AML
arm group label: LOP628 - Solid Tumor
arm group label: LOP628 - Solid Tumor Expansion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Belgium
country: Netherlands
country: Spain
country: France
country: Germany
country: Italy
country: United States
responsible party type: Sponsor
mesh term: Leukemia, Myeloid, Acute