<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/NCT03234712</url>
  </required_header>
  <id_info>
    <org_study_id>M16-438</org_study_id>
    <nct_id>NCT03234712</nct_id>
  </id_info>
  <brief_title>A Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)</brief_title>
  <official_title>A Phase 1 Study Evaluating the Safety, Pharmacokinetics, and Anti-tumor Activity of ABBV-321 in Subjects With Advanced Solid Tumors Associated With Overexpression of the Epidermal Growth Factor Receptor (EGFR)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AbbVie</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, Phase 1, dose-escalation study to determine the maximum tolerated dose&#xD;
      (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary&#xD;
      efficacy, and pharmacokinetic (PK) profile of ABBV-321 for participants with advanced solid&#xD;
      tumors likely to overexpress the epidermal growth factor receptor (EGFR). The study will&#xD;
      consist of 2 phases: Dose Escalation Phase and Expansion Phase.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 10, 2017</start_date>
  <completion_date type="Actual">April 14, 2021</completion_date>
  <primary_completion_date type="Actual">April 14, 2021</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>AUCt for ABBV-321</measure>
    <time_frame>Up to 78 days post dose</time_frame>
    <description>Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-321</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC∞ for ABBV-321</measure>
    <time_frame>Up to 78 days post dose</time_frame>
    <description>AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax of ABBV-321</measure>
    <time_frame>Up to 78 days post dose</time_frame>
    <description>Time to Cmax (Tmax) of ABBV-321</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal phase elimination rate constant (β) for ABBV-321</measure>
    <time_frame>Up to 78 days post dose</time_frame>
    <description>Terminal phase elimination rate constant (β)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of ABBV-321</measure>
    <time_frame>Up to 78 days post dose</time_frame>
    <description>Maximum observed plasma concentration (Cmax) of ABBV-321</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for ABBV-321</measure>
    <time_frame>Minimum first cycle of dosing (up to 28 days)</time_frame>
    <description>The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Phase</description>
  </primary_outcome>
  <primary_outcome>
    <measure>t1/2 for ABBV-321</measure>
    <time_frame>Up to 78 days post dose</time_frame>
    <description>Terminal elimination half-life (t1/2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321</measure>
    <time_frame>Minimum first cycle of dosing (up to 28 days)</time_frame>
    <description>The MTD of ABBV-321 will be determined during the dose escalation phase of the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>Up to approximately 5 years</time_frame>
    <description>PFS is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Up to approximately 5 years</time_frame>
    <description>DOR for a given participant is defined as the number of days from the day CR or PR (whichever is recorded first) occurred to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>DCR is defined as the proportion of participants with objective evidence of complete response (CR), partial response (PR) or stable disease (SD); a participants best overall response assignment of SD must be maintained for at least 6 weeks since the first dose date of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to progression (TTP)</measure>
    <time_frame>Up to approximately 5 years</time_frame>
    <description>TTP is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST version 1.1 or RANO criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in QTcF</measure>
    <time_frame>Up to 61 days post dose</time_frame>
    <description>QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to approximately 5 years</time_frame>
    <description>OS is defined as number of days from the date of the first dose to the date of death for all dosed participants. For participants who are not deceased, the data will be censored at the last known date to be alive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>ORR is defined as the proportion of participants with a response of partial response (PR) or better; Response Assessment in Neuro-Oncology (RANO) criteria will be used for glioblastoma (GBM) participants, and Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria will be used for all other participants.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">62</enrollment>
  <condition>Advanced Solid Tumors Cancer</condition>
  <arm_group>
    <arm_group_label>ABBV-321</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-321 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ABBV-321</intervention_name>
    <description>Intravenous infusion</description>
    <arm_group_label>ABBV-321</arm_group_label>
    <other_name>Serclutamab Talirine</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.&#xD;
&#xD;
          -  Histologically or cytologically confirmed solid tumor of one of the following types&#xD;
             associated with overexpression of Epidermal Growth Factor Receptor (EGFR). (For&#xD;
             Expansion Phase: Subjects must have EGFR overexpression demonstrated by central&#xD;
             assessment or Sponsor selected test).&#xD;
&#xD;
        Dose Escalation Phase:&#xD;
&#xD;
          -  Colorectal cancer (CRC), Glioblastoma (GBM), squamous cell carcinoma of the head and&#xD;
             neck (HNSCC), non-small cell lung cancer (NSCLC), bladder, cervical, esophageal,&#xD;
             kidney or sarcoma.&#xD;
&#xD;
          -  Participants must have disease that has progressed on prior treatment and is not&#xD;
             amenable to surgical resection or other approved therapeutic options with curative&#xD;
             intent. Participants must not be eligible for, or has refused further therapy that is&#xD;
             likely to provide a survival benefit.&#xD;
&#xD;
          -  Must have measureable disease as per RECIST Version 1.1 or RANO (for GBM).&#xD;
&#xD;
          -  Minimum life expectancy of at least 12 weeks.&#xD;
&#xD;
        Expansion Phase (Solid Tumor Cohort):&#xD;
&#xD;
          -  Histologically or cytologically confirmed advanced solid tumor.&#xD;
&#xD;
          -  Participants must have disease that has progressed on prior treatment and is not&#xD;
             amenable to surgical resection or other approved therapeutic options with curative&#xD;
             intent.&#xD;
&#xD;
          -  Must have measureable disease as per RECIST Version 1.1.&#xD;
&#xD;
          -  Minimum life expectancy of at least 12 weeks.&#xD;
&#xD;
        Expansion Phase (GBM Cohort Only):&#xD;
&#xD;
          -  Participant has recurrent primary (de novo) glioblastoma histologically confirmed at&#xD;
             any time from initial diagnosis through latest recurrence.&#xD;
&#xD;
          -  Participant has recurrent GBM per Response Evaluation in Neuro-Oncology (RANO)&#xD;
             requirements.&#xD;
&#xD;
          -  Tumor is measurable according to RANO criteria.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active uncontrolled infection National Cancer Institute Common Terminology Criteria&#xD;
             for Adverse Events (NCI CTCAE Grade greater than or equal to 3).&#xD;
&#xD;
          -  New York Heart Association (NYHA) Class III or IV heart failure and/or ejection&#xD;
             fraction of &lt; 40% as measured by echocardiogram at screening.&#xD;
&#xD;
          -  Unstable angina pectoris or cardiac ventricular arrhythmia.&#xD;
&#xD;
          -  Myocardial infarction or cerebrovascular accident (CVA) within 6 months.&#xD;
&#xD;
          -  Documented history of capillary leak syndrome within 6 months of study enrollment.&#xD;
&#xD;
          -  Grade 2 or higher peripheral edema, ascites, pleural, or pericardial effusion within 4&#xD;
             weeks of study enrollment or any history of recurrent grade 2 or higher effusions&#xD;
             requiring ongoing drainage.&#xD;
&#xD;
          -  Active keratitis or current corneal disorder.&#xD;
&#xD;
          -  Laser-assisted in situ keratomileusis (LASIK) procedure within the last 1 year or&#xD;
             cataract surgery within the last 3 months.&#xD;
&#xD;
          -  Major surgery (including opening of the abdomen, chest) within 21 days of the first&#xD;
             dose of study drug.&#xD;
&#xD;
          -  Uncontrolled metastases from an extracranial solid tumor to the central nervous system&#xD;
             (CNS). Participants with brain metastases from an extracranial solid tumor are&#xD;
             eligible after definitive therapy provided they are asymptomatic for at least 2 weeks&#xD;
             prior to first dose of ABBV-321.&#xD;
&#xD;
          -  No history of medical condition resulting in nephrotic range proteinuria.&#xD;
&#xD;
          -  Participants must not have been treated in anticancer therapy including chemotherapy,&#xD;
             immunotherapy, radiotherapy, hormonal therapy, biologic therapy or investigational&#xD;
             anti-cancer therapy within a period of 21 days or herbal anticancer therapy within 7&#xD;
             days prior to the first dose of study drug.&#xD;
&#xD;
          -  For approved targeted small molecules, a washout period of 5 half-lives is adequate&#xD;
             (no washout period required for subjects currently on erlotinib)&#xD;
&#xD;
          -  Participant must not have been in more than three lines of systemic cytotoxic therapy&#xD;
             (excluding adjuvant and neoadjuvant therapy)&#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>ABBVIE INC.</last_name>
    <role>Study Director</role>
    <affiliation>AbbVie</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Highlands Oncology Group /ID# 166132</name>
      <address>
        <city>Springdale</city>
        <state>Arkansas</state>
        <zip>72762</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Angeles Clinic and Researc /ID# 166133</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Davis Comprehensive Cancer Center /ID# 215012</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University Feinberg School of Medicine /ID# 165191</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611-2927</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago /ID# 166064</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northshore University Health System Dermatology Clinical Trials Unit /ID# 201095</name>
      <address>
        <city>Skokie</city>
        <state>Illinois</state>
        <zip>60077</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kentucky Markey Cancer Center /ID# 217665</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536-7001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute /ID# 212920</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University-School of Medicine /ID# 214955</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia Univ Medical Center /ID# 167184</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032-3725</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stony Brook University Hospital /ID# 216976</name>
      <address>
        <city>Stony Brook</city>
        <state>New York</state>
        <zip>11794-8183</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center /ID# 166135</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710-3000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lifespan Cancer Institute at Rhode Island Hospital /ID# 168600</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903-4923</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Texas Accelerated Research Therapeutics /ID# 166134</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern Cancer Institute /ID# 166138</name>
      <address>
        <city>St Leonards</city>
        <state>New South Wales</state>
        <zip>2065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Health /ID# 217435</name>
      <address>
        <city>Clayton</city>
        <state>Victoria</state>
        <zip>3168</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Hospital /ID# 166137</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheba Medical Center /ID# 166398</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5239424</zip>
        <country>Israel</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Israel</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Korea, Republic of</country>
    <country>Taiwan</country>
  </removed_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>May 5, 2021</last_update_submitted>
  <last_update_submitted_qc>May 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Advanced Solid Tumors</keyword>
  <keyword>Epidermal Growth Factor Receptor (EGFR)</keyword>
  <keyword>Squamous cell carcinoma of the head and neck (HNSCC)</keyword>
  <keyword>non-small cell lung cancer (NSCLC)</keyword>
  <keyword>Glioblastoma (GBM)</keyword>
  <keyword>Cancer</keyword>
  <keyword>overexpression of Epidermal Growth Factor Receptor (EGFR)</keyword>
  <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/NCT03234712
org study id: M16-438
nct id: NCT03234712
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This is an open-label, Phase 1, dose-escalation study to determine the maximum tolerated dose
      (MTD) and the recommended phase two dose (RPTD), and to assess the safety, preliminary
      efficacy, and pharmacokinetic (PK) profile of ABBV-321 for participants with advanced solid
      tumors likely to overexpress the epidermal growth factor receptor (EGFR). The study will
      consist of 2 phases: Dose Escalation Phase and Expansion Phase.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUCt for ABBV-321
time frame: Up to 78 days post dose
description: Area Under the Plasma Concentration-time Curve from Time 0 to the Time of the Last Measurable Concentration (AUCt) for ABBV-321
measure: AUC∞ for ABBV-321
time frame: Up to 78 days post dose
description: AUC∞ is the area under the plasma concentration-time curve from Time 0 to infinite time.
measure: Tmax of ABBV-321
time frame: Up to 78 days post dose
description: Time to Cmax (Tmax) of ABBV-321
measure: Terminal phase elimination rate constant (β) for ABBV-321
time frame: Up to 78 days post dose
description: Terminal phase elimination rate constant (β)
measure: Cmax of ABBV-321
time frame: Up to 78 days post dose
description: Maximum observed plasma concentration (Cmax) of ABBV-321
measure: Dose Escalation Phase: Recommended Phase 2 dose (RPTD) for ABBV-321
time frame: Minimum first cycle of dosing (up to 28 days)
description: The RPTD will be determined using available safety and pharmacokinetics data upon completion of the Dose Escalation Phase
measure: t1/2 for ABBV-321
time frame: Up to 78 days post dose
description: Terminal elimination half-life (t1/2)
measure: Dose Escalation Phase: Maximum tolerated dose (MTD) of ABBV-321
time frame: Minimum first cycle of dosing (up to 28 days)
description: The MTD of ABBV-321 will be determined during the dose escalation phase of the study.
measure: Progression-Free Survival (PFS)
time frame: Up to approximately 5 years
description: PFS is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.
measure: Duration of Response (DOR)
time frame: Up to approximately 5 years
description: DOR for a given participant is defined as the number of days from the day CR or PR (whichever is recorded first) occurred to the earliest date of disease progression per RECIST 1.1 or RANO criteria or death, whichever occurred first.
measure: Disease Control Rate (DCR)
time frame: Up to 5 years
description: DCR is defined as the proportion of participants with objective evidence of complete response (CR), partial response (PR) or stable disease (SD); a participants best overall response assignment of SD must be maintained for at least 6 weeks since the first dose date of study drug.
measure: Time to progression (TTP)
time frame: Up to approximately 5 years
description: TTP is defined as the number of days from the first dose date to the earliest date of disease progression per RECIST version 1.1 or RANO criteria.
measure: Change from Baseline in QTcF
time frame: Up to 61 days post dose
description: QT interval measurement corrected by Fridericia's formula (QTcF) change from baseline
measure: Overall Survival (OS)
time frame: Up to approximately 5 years
description: OS is defined as number of days from the date of the first dose to the date of death for all dosed participants. For participants who are not deceased, the data will be censored at the last known date to be alive.
measure: Objective response rate (ORR)
time frame: Up to 5 years
description: ORR is defined as the proportion of participants with a response of partial response (PR) or better; Response Assessment in Neuro-Oncology (RANO) criteria will be used for glioblastoma (GBM) participants, and Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria will be used for all other participants.
arm group label: ABBV-321
arm group type: Experimental
description: ABBV-321 will be administered via intravenous infusion at escalating dose levels until the maximum tolerated dose is reached and a recommended Phase 2 dose is determined.
intervention type: Drug
intervention name: ABBV-321
description: Intravenous infusion
arm group label: ABBV-321
other name: Serclutamab Talirine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ABBVIE INC.
role: Study Director
affiliation: AbbVie
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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country: Australia
country: Israel
country: United States
country: Korea, Republic of
country: Taiwan
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No