<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/NCT04417465</url>
  </required_header>
  <id_info>
    <org_study_id>M20-124</org_study_id>
    <secondary_id>2020-000639-28</secondary_id>
    <nct_id>NCT04417465</nct_id>
  </id_info>
  <brief_title>First In Human Study With ABBV-CLS-579 When Given Alone and In Combination In Participants With Locally Advanced Or Metastatic Tumors</brief_title>
  <official_title>A Phase 1, Multi-center, Open Label First-in-Human Study With ABBV-CLS-579 Alone and in Combination in Subjects With Locally Advanced or Metastatic Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Calico Life Sciences LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AbbVie</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Calico Life Sciences LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see how safe and effective ABBV-CLS-579 is when used alone&#xD;
      and in combination with a PD-1 target agent or with a VEGF TKI.&#xD;
&#xD;
      ABBV-CLS-579 is an investigational drug being developed for the treatment of tumors.&#xD;
&#xD;
      The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-579 as&#xD;
      monotherapy and in combination. The study will be conducted in three parts. Part 1&#xD;
      Monotherapy Dose Escalation, Part 2 Combination Dose Escalation, and Part 3 Combination Dose&#xD;
      Expansion.&#xD;
&#xD;
      Part 1, ABBV-CLS-579 will be administered alone in escalating dose levels to eligible&#xD;
      subjects who have advanced solid tumors.&#xD;
&#xD;
      Part 2, ABBV-CLS-579 will be administered at escalating dose levels in combination with a&#xD;
      PD-1 targeting agent to eligible subjects who have advanced solid tumors.&#xD;
&#xD;
      Part 3, ABBV-CLS-579 will be administered at the determined recommended dose in combination&#xD;
      with a PD-1 target agent or with a VEGFR TKI in subjects with locally advanced or metastatic,&#xD;
      relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory&#xD;
      non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC).&#xD;
&#xD;
      Adult participants with a diagnosis of some solid tumors for which no effective standard&#xD;
      therapy exists or has failed will be enrolled. Participants will receive study treatment&#xD;
      until disease progresses or discontinued.&#xD;
&#xD;
      There may be a higher treatment burden for participants in this trial compared to their&#xD;
      standard of care. Participants will attend regular visits during the course of the study at a&#xD;
      hospital or clinic. The effect of the treatment will be checked by medical assessments, blood&#xD;
      tests, checking for side effects, and completing questionnaires.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 3, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>Maximum plasma/serum concentration of ABBV-CLS-579</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>Maximum plasma/serum concentration of Metabolite M4</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Plasma/Serum Concentration (Cmax) Of PD-1 Inhibitor</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>Maximum plasma/serum concentration of PD-1 inhibitor</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>Maximum plasma/serum concentration of VEGFR TKI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time To Cmax (Tmax) Of ABBV-CLS-579</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>The amount of time taken to reach Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time To Cmax (Tmax) Of Metabolite M4</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>The amount of time taken to reach Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time To Cmax (Tmax) Of PD-1 Inhibitor</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>The amount of time taken to reach Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time To Cmax (Tmax) Of VEGFR TKI</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>The amount of time taken to reach Cmax</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-579</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>Terminal phase elimination rate constant (β or Beta)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Rate Constant (β) Of Metabolite M4</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>Terminal phase elimination rate constant (β or Beta)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Rate Constant (β) Of PD-1 Inhibitor</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>Terminal phase elimination rate constant (β or Beta)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Rate Constant (β) Of VEGFR TKI</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>Terminal phase elimination rate constant (β or Beta)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Half-Life (t1/2) Of ABBV-CLS-579</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>Terminal phase elimination half-life (t1/2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Half-Life (t1/2) Of Metabolite M4</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>Terminal phase elimination half-life (t1/2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Half-Life (t1/2) Of PD-1 Inhibitor</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>Terminal phase elimination half-life (t1/2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Phase Elimination Half-Life (t1/2) Of VEGFR TKI</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>Terminal phase elimination half-life (t1/2)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4</measure>
    <time_frame>Baseline Up to Approximately Day 44</time_frame>
    <description>AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI</measure>
    <time_frame>Baseline Up to Approximately Day 64</time_frame>
    <description>AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>The Expansion Dose and/or MTD of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>The Expansion Dose and/or MTD of ABBV-CLS-579 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Base On Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, of ABBV-CLS-579 in locally or metastatic HNSCC, NSCLC, MSI-H tumors, and advanced ccRCC</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective Response Rate (ORR) on RECIST v1.1, of ABBV-CLS-579 administered in combination with VEGFR TKI in advanced ccRCC</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline QTc</measure>
    <time_frame>Baseline through Study Completion (approximately 3 years)</time_frame>
    <description>QT prolongation is measured by the QT interval measurement corrected for heart rate (QTc) change from baseline</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">263</enrollment>
  <condition>Advanced Solid Tumors Cancer</condition>
  <arm_group>
    <arm_group_label>Monotherapy Dose Escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination Dose Escalation with PD-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Backfill Cohorts with Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Backfill Cohorts in Combination with PD-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination Expansion with PD-1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-CLS-579 will be administered at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), microsatellite instability-high (MSI-H) tumors, and advanced clear cell renal cell carcinoma (ccRCC)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Combination Expansion with VEGFR TKI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ABBV-CLS-579 will be administered at the determined recommended dose in combination with Vascular Endothelial Growth (VEGFR) Factor Receptor Tyrosine Kinase Inhibitor (TKI) in subjects with advanced ccRCC.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ABBV-CLS-579</intervention_name>
    <description>Oral Capsule</description>
    <arm_group_label>Backfill Cohorts in Combination with PD-1</arm_group_label>
    <arm_group_label>Backfill Cohorts with Monotherapy</arm_group_label>
    <arm_group_label>Combination Dose Escalation with PD-1</arm_group_label>
    <arm_group_label>Combination Expansion with PD-1</arm_group_label>
    <arm_group_label>Combination Expansion with VEGFR TKI</arm_group_label>
    <arm_group_label>Monotherapy Dose Escalation</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PD-1 inhibitor</intervention_name>
    <description>Intravenous (IV) infusion</description>
    <arm_group_label>Backfill Cohorts in Combination with PD-1</arm_group_label>
    <arm_group_label>Combination Dose Escalation with PD-1</arm_group_label>
    <arm_group_label>Combination Expansion with PD-1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>VEGFR TKI</intervention_name>
    <description>Oral Tablet</description>
    <arm_group_label>Combination Expansion with VEGFR TKI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must weigh at least 35 kilograms (kg).&#xD;
&#xD;
          -  For Monotherapy and Combination Dose Escalation:&#xD;
&#xD;
               -  Histologically or cytologically proven metastatic or locally advanced tumors&#xD;
                  (with measurable disease defined by Response Evaluation Criteria In Solid Tumors&#xD;
                  [RECIST] v1.1), for which no effective standard therapy exists, or where standard&#xD;
                  therapy has failed. Participants must have received at least 1 prior systemic&#xD;
                  anticancer therapy for the indication being considered.&#xD;
&#xD;
          -  For Combination Dose Expansion:&#xD;
&#xD;
               -  For the following tumor types, the subject must have received at least 1 prior&#xD;
                  line containing PD-1/PD-L1 target therapy.&#xD;
&#xD;
        Indication with outcome of Prior PD-1/PD-L1 Targeted Therapy and other disease&#xD;
        characteristics:&#xD;
&#xD;
          -  NSCLC&#xD;
&#xD;
               -  Relapsed: Tumors express PD-L1 (TPS ≥ 1%) as determined by the FDA-approved&#xD;
                  Agilent PD-L1 IHC 22C3 pharmDx kit&#xD;
&#xD;
               -  Refractory: Tumors express PD-L1 (TPS ≥ 1%) as determined by the FDA-approved&#xD;
                  Agilent PD-L1 IHC 22C3 pharmDx kit&#xD;
&#xD;
          -  ccRCC&#xD;
&#xD;
               -  Relapsed or Refractory: Advanced disease (locally advanced or metastatic)&#xD;
&#xD;
          -  MSI-H tumors&#xD;
&#xD;
               -  Refractory: Locally advanced or metastatic MSI-H tumors whose tumors are&#xD;
                  determined to have a MSI-H status by PCR or NGS tests, or dMMR by IHC tests.&#xD;
&#xD;
          -  HNSCC&#xD;
&#xD;
               -  Relapsed or Refractory: Tumors express PD-L1 (CPS ≥ 1] as determined by the FDA&#xD;
                  approved PD-L1 Agilent IHC 22C3 pharmDx kit&#xD;
&#xD;
          -  For Combination Dose Expansion:&#xD;
&#xD;
               -  Locally advanced or metastatic, advanced ccRCC who have relapsed after at least 1&#xD;
                  prior VEGFR TKI therapy&#xD;
&#xD;
          -  Received at least 1 prior line containing PD 1/PD L1 targeted therapy with a best&#xD;
             response by RECIST v1.1 of CR/PR (any duration) or stable disease (for greater than 6&#xD;
             months)&#xD;
&#xD;
          -  Received at least 1 prior line containing PD-1/PD-L1 targeted therapy and have had&#xD;
             disease progression (in the absence of best response of CR/PR/stable disease by RECIST&#xD;
             v1.1) with PD 1/PD L1 targeted therapy&#xD;
&#xD;
          -  An Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.&#xD;
&#xD;
          -  Life expectancy of ≥ 12 weeks.&#xD;
&#xD;
          -  Laboratory values meeting protocol criteria.&#xD;
&#xD;
          -  If the subject is on anticoagulant therapy, INR must be within therapeutic goal.&#xD;
&#xD;
          -  QT interval corrected for heart rate &lt; 450 msec (using Fridericia's correction), and&#xD;
             no clinically significant electrocardiographic findings.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Untreated brain or meningeal metastases (participants with history of metastases are&#xD;
             eligible provide they do not require ongoing steroid treatment and have shown clinical&#xD;
             and radiographic stability for at least 28 days after definitive therapy).&#xD;
&#xD;
          -  Unresolved Grade 2 or higher toxicities related to previous anticancer therapy except&#xD;
             alopecia.&#xD;
&#xD;
          -  History of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
          -  Recent history (within 6 months) of congestive heart failure (defined as New York&#xD;
             Heart Association, Class 2 or higher), ischemic cardiovascular event, pericarditis, or&#xD;
             clinically significant pericardial effusion, cardiac arrythmia or peripheral artery&#xD;
             disease.&#xD;
&#xD;
          -  Recent history (within 6 months) of Childs-Pugh B or C classification of liver&#xD;
             disease.&#xD;
&#xD;
          -  History of clinically significant medical and/or psychiatric conditions or any other&#xD;
             reason that, in the opinion of the investigator, would interfere with participation in&#xD;
             this study or would make the participant an unsuitable candidate to receive study&#xD;
             drug.&#xD;
&#xD;
          -  History of uncontrolled, clinically significant endocrinopathy.&#xD;
&#xD;
          -  Known gastrointestinal disorders making absorption of oral medications problematic.&#xD;
             Inability to swallow capsules.&#xD;
&#xD;
          -  If treated with anti-programmed cell death protein-1 (aPD-1)/antiprogrammed cell death&#xD;
             protein-ligand 1(aPD-L1) targeting or other immunostimulatory agents in the past:&#xD;
             excluded if had prior pneumonitis, prior Grade 3 or higher immune mediated toxicity,&#xD;
             hypersensitivity to administered drug or drug related toxicity requiring&#xD;
             discontinuation.&#xD;
&#xD;
          -  Active autoimmune disease requiring systemic treatment in past 2-years (exceptions for&#xD;
             endocrinopathies, vitiligo or atopic conditions)&#xD;
&#xD;
          -  History of solid organ transplant or allogeneic stem cell transplant.&#xD;
&#xD;
          -  History of interstitial lung disease or pneumonitis.&#xD;
&#xD;
          -  Major surgery ≤ 28 days prior to first dose of study drug.&#xD;
&#xD;
          -  Poorly controlled hypertension&#xD;
&#xD;
          -  History of hemorrhage, including hemoptysis, hematemesis, or melena&#xD;
&#xD;
          -  History of other malignancy, with the following exceptions:&#xD;
&#xD;
               -  No known active disease present for within 3 years before first dose of study&#xD;
                  treatment and felt to be at low recurrence by investigator&#xD;
&#xD;
               -  Adequately treated non-melanoma skin cancer or lentigo maligna without evidence&#xD;
                  of disease&#xD;
&#xD;
               -  Adequately treated carcinoma in situ without evidence of disease&#xD;
&#xD;
          -  Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection&#xD;
             per local testing practices.&#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_contact>
    <last_name>ABBVIE CALL CENTER</last_name>
    <phone>847.283.8955</phone>
    <email>abbvieclinicaltrials@abbvie.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Highlands Oncology Group Springdale</name>
      <address>
        <city>Springdale</city>
        <state>Arkansas</state>
        <zip>72762</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rachel Richmond</last_name>
      <phone>479-872-8130</phone>
    </contact>
    <investigator>
      <last_name>Joseph Beck</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06519</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Erina Sarker</last_name>
      <phone>475-301-4070</phone>
    </contact>
    <investigator>
      <last_name>Patricia LoRusso</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Fort Wayne Medical Oncology and Hematology</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46804</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Brandy Irmiter</last_name>
      <phone>206-436-0800</phone>
    </contact>
    <investigator>
      <last_name>Sunil Babu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carolina BioOncology Institute</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <zip>28078</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sydney Noldin</last_name>
      <phone>704-947-6599</phone>
    </contact>
    <investigator>
      <last_name>John Powderly</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sarah Behr</last_name>
      <phone>412-623-6028</phone>
    </contact>
    <investigator>
      <last_name>Jason Luke</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hopital Saint-Andre</name>
      <address>
        <city>Bordeaux</city>
        <zip>33000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>05-56-79-47-08</phone>
    </contact>
    <investigator>
      <last_name>Amaury Daste</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94805</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>01-42-11-46-72</phone>
    </contact>
    <investigator>
      <last_name>Rastislav Bahleda</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Chaim Sheba Medical Center</name>
      <address>
        <city>Ramat Gan</city>
        <zip>5262100</zip>
        <country>Israel</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>972-3-5304498</phone>
    </contact>
    <investigator>
      <last_name>Talia Golan</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Kashiwa-Shi</city>
        <state>Chiba</state>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>81-04-7133-1111</phone>
    </contact>
    <investigator>
      <last_name>Nobuaki Matsubara</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Wakayama Medical University Hospital</name>
      <address>
        <city>Wakayama-Shi</city>
        <state>Wakayama</state>
        <zip>641-8510</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>81-073-447-2300</phone>
    </contact>
    <investigator>
      <last_name>Toshio Shimizu</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital</name>
      <address>
        <city>Chuo-ku, Tokyo</city>
        <zip>104-0045</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>81-335422511</phone>
    </contact>
    <investigator>
      <last_name>Noboru Yamamoto</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>82-2-741-4221</phone>
    </contact>
    <investigator>
      <last_name>Do-Youn Oh</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>34 915504800</phone>
      <phone_ext>2805</phone_ext>
    </contact>
    <investigator>
      <last_name>Victor Moreno Garcia</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>+34 913-908-923</phone>
    </contact>
    <investigator>
      <last_name>Jon Zugazagoitia Fraile</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario HM Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>34-917567825</phone>
    </contact>
    <investigator>
      <last_name>Emiliano Calvo Aller</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>951-032-250</phone>
    </contact>
    <investigator>
      <last_name>Javier Garcia Corbacho</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <phone>886-2-23123456</phone>
      <phone_ext>67680</phone_ext>
    </contact>
    <investigator>
      <last_name>Chia-Chi Lin</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
    <country>Israel</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>July 19, 2023</last_update_submitted>
  <last_update_submitted_qc>July 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Tumor</keyword>
  <keyword>ABBV-CLS-579</keyword>
  <keyword>PD-1</keyword>
  <keyword>VEGFR TKI</keyword>
  <keyword>ccRCC</keyword>
  <keyword>NSCLC</keyword>
  <keyword>MSI-H</keyword>
  <keyword>HNSCC</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasm Metastasis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immune Checkpoint Inhibitors</mesh_term>
  </intervention_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/NCT04417465
org study id: M20-124
secondary id: 2020-000639-28
nct id: NCT04417465
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to see how safe and effective ABBV-CLS-579 is when used alone
      and in combination with a PD-1 target agent or with a VEGF TKI.

      ABBV-CLS-579 is an investigational drug being developed for the treatment of tumors.

      The trial aims to establish a safe, tolerable, and efficacious dose of ABBV-CLS-579 as
      monotherapy and in combination. The study will be conducted in three parts. Part 1
      Monotherapy Dose Escalation, Part 2 Combination Dose Escalation, and Part 3 Combination Dose
      Expansion.

      Part 1, ABBV-CLS-579 will be administered alone in escalating dose levels to eligible
      subjects who have advanced solid tumors.

      Part 2, ABBV-CLS-579 will be administered at escalating dose levels in combination with a
      PD-1 targeting agent to eligible subjects who have advanced solid tumors.

      Part 3, ABBV-CLS-579 will be administered at the determined recommended dose in combination
      with a PD-1 target agent or with a VEGFR TKI in subjects with locally advanced or metastatic,
      relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory
      non-small cell lung cancer (NSCLC), and advanced clear cell renal cell carcinoma (ccRCC).

      Adult participants with a diagnosis of some solid tumors for which no effective standard
      therapy exists or has failed will be enrolled. Participants will receive study treatment
      until disease progresses or discontinued.

      There may be a higher treatment burden for participants in this trial compared to their
      standard of care. Participants will attend regular visits during the course of the study at a
      hospital or clinic. The effect of the treatment will be checked by medical assessments, blood
      tests, checking for side effects, and completing questionnaires.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Observed Plasma/Serum Concentration (Cmax) Of ABBV-CLS-579
time frame: Baseline Up to Approximately Day 44
description: Maximum plasma/serum concentration of ABBV-CLS-579
measure: Maximum Observed Plasma/Serum Concentration (Cmax) Of Metabolite M4
time frame: Baseline Up to Approximately Day 44
description: Maximum plasma/serum concentration of Metabolite M4
measure: Maximum Observed Plasma/Serum Concentration (Cmax) Of PD-1 Inhibitor
time frame: Baseline Up to Approximately Day 64
description: Maximum plasma/serum concentration of PD-1 inhibitor
measure: Maximum Observed Plasma/Serum Concentration (Cmax) Of VEGFR TKI
time frame: Baseline Up to Approximately Day 64
description: Maximum plasma/serum concentration of VEGFR TKI
measure: Time To Cmax (Tmax) Of ABBV-CLS-579
time frame: Baseline Up to Approximately Day 44
description: The amount of time taken to reach Cmax
measure: Time To Cmax (Tmax) Of Metabolite M4
time frame: Baseline Up to Approximately Day 44
description: The amount of time taken to reach Cmax
measure: Time To Cmax (Tmax) Of PD-1 Inhibitor
time frame: Baseline Up to Approximately Day 64
description: The amount of time taken to reach Cmax
measure: Time To Cmax (Tmax) Of VEGFR TKI
time frame: Baseline Up to Approximately Day 64
description: The amount of time taken to reach Cmax
measure: Terminal Phase Elimination Rate Constant (β) Of ABBV-CLS-579
time frame: Baseline Up to Approximately Day 44
description: Terminal phase elimination rate constant (β or Beta)
measure: Terminal Phase Elimination Rate Constant (β) Of Metabolite M4
time frame: Baseline Up to Approximately Day 44
description: Terminal phase elimination rate constant (β or Beta)
measure: Terminal Phase Elimination Rate Constant (β) Of PD-1 Inhibitor
time frame: Baseline Up to Approximately Day 64
description: Terminal phase elimination rate constant (β or Beta)
measure: Terminal Phase Elimination Rate Constant (β) Of VEGFR TKI
time frame: Baseline Up to Approximately Day 64
description: Terminal phase elimination rate constant (β or Beta)
measure: Terminal Phase Elimination Half-Life (t1/2) Of ABBV-CLS-579
time frame: Baseline Up to Approximately Day 44
description: Terminal phase elimination half-life (t1/2)
measure: Terminal Phase Elimination Half-Life (t1/2) Of Metabolite M4
time frame: Baseline Up to Approximately Day 44
description: Terminal phase elimination half-life (t1/2)
measure: Terminal Phase Elimination Half-Life (t1/2) Of PD-1 Inhibitor
time frame: Baseline Up to Approximately Day 64
description: Terminal phase elimination half-life (t1/2)
measure: Terminal Phase Elimination Half-Life (t1/2) Of VEGFR TKI
time frame: Baseline Up to Approximately Day 64
description: Terminal phase elimination half-life (t1/2)
measure: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of ABBV-CLS-579
time frame: Baseline Up to Approximately Day 44
description: AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
measure: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of Metabolite M4
time frame: Baseline Up to Approximately Day 44
description: AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
measure: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of PD-1 Inhibitor
time frame: Baseline Up to Approximately Day 64
description: AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
measure: Area Under The Plasma Or Serum Concentration-Time Curve (AUC) Of VEGFR TKI
time frame: Baseline Up to Approximately Day 64
description: AUC is the area under the serum concentration versus time curve of the last measurable concentration prior to next dose
measure: Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579
time frame: Baseline through Study Completion (approximately 3 years)
description: The Expansion Dose and/or MTD of ABBV-CLS-579 will be determined during the monotherapy dose escalation phase of the study
measure: Recommended Expansion Dose and/or Maximum Tolerated Dose of ABBV-CLS-579 and a PD-1 Inhibitor
time frame: Baseline through Study Completion (approximately 3 years)
description: The Expansion Dose and/or MTD of ABBV-CLS-579 and PD-1 inhibitor will be determined during the combination therapy dose escalation phase of the study
measure: Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Base On Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, of ABBV-CLS-579 in locally or metastatic HNSCC, NSCLC, MSI-H tumors, and advanced ccRCC
time frame: Baseline through Study Completion (approximately 3 years)
description: ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
measure: Objective Response Rate (ORR) on RECIST v1.1, of ABBV-CLS-579 administered in combination with VEGFR TKI in advanced ccRCC
time frame: Baseline through Study Completion (approximately 3 years)
description: ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
measure: Objective Response Rate (ORR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
time frame: Baseline through Study Completion (approximately 3 years)
description: ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
measure: Objective Response Rate (ORR) Of ABBV-CLS-579 Monotherapy Based On Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
time frame: Baseline through Study Completion (approximately 3 years)
description: ORR is defined as achieving complete response (CR) or partial response (PR) based on RECIST 1.1 criteria on treatment
measure: Best Overall Response (BOR) Of ABBV-CLS-579 Monotherapy Based On RECIST v1.1
time frame: Baseline through Study Completion (approximately 3 years)
description: BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
measure: Best Overall Response (BOR) Of ABBV-CLS-579 And PD-1 Targeting Agent Based On RECIST v1.1
time frame: Baseline through Study Completion (approximately 3 years)
description: BOR is defined as the best response recorded from the start of the treatment until disease progression/recurrence
measure: Change from Baseline QTc
time frame: Baseline through Study Completion (approximately 3 years)
description: QT prolongation is measured by the QT interval measurement corrected for heart rate (QTc) change from baseline
arm group label: Monotherapy Dose Escalation
arm group type: Experimental
description: ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors
arm group label: Combination Dose Escalation with PD-1
arm group type: Experimental
description: ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors
arm group label: Backfill Cohorts with Monotherapy
arm group type: Experimental
description: ABBV-CLS-579 will be administered as a monotherapy in subjects with solid tumors
arm group label: Backfill Cohorts in Combination with PD-1
arm group type: Experimental
description: ABBV-CLS-579 will be administered in combination with Programmed Cell Death-1 Inhibitor in subjects with solid tumors
arm group label: Combination Expansion with PD-1
arm group type: Experimental
description: ABBV-CLS-579 will be administered at the determined recommended dose in subjects with locally advanced or metastatic, relapsed or refractory head and neck squamous cell carcinoma (HNSCC), relapsed or refractory non-small cell lung cancer (NSCLC), microsatellite instability-high (MSI-H) tumors, and advanced clear cell renal cell carcinoma (ccRCC)
arm group label: Combination Expansion with VEGFR TKI
arm group type: Experimental
description: ABBV-CLS-579 will be administered at the determined recommended dose in combination with Vascular Endothelial Growth (VEGFR) Factor Receptor Tyrosine Kinase Inhibitor (TKI) in subjects with advanced ccRCC.
intervention type: Drug
intervention name: ABBV-CLS-579
description: Oral Capsule
arm group label: Backfill Cohorts in Combination with PD-1
arm group label: Backfill Cohorts with Monotherapy
arm group label: Combination Dose Escalation with PD-1
arm group label: Combination Expansion with PD-1
arm group label: Combination Expansion with VEGFR TKI
arm group label: Monotherapy Dose Escalation
intervention type: Drug
intervention name: PD-1 inhibitor
description: Intravenous (IV) infusion
arm group label: Backfill Cohorts in Combination with PD-1
arm group label: Combination Dose Escalation with PD-1
arm group label: Combination Expansion with PD-1
intervention type: Drug
intervention name: VEGFR TKI
description: Oral Tablet
arm group label: Combination Expansion with VEGFR TKI
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: ABBVIE CALL CENTER
phone: 847.283.8955
email: abbvieclinicaltrials@abbvie.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
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facility: 
status: Recruiting
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
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facility: 
status: Recruiting
contact: 
investigator: 
country: France
country: Israel
country: Japan
country: Korea, Republic of
country: Spain
country: Taiwan
country: United States
responsible party type: Sponsor
mesh term: Neoplasm Metastasis
mesh term: Immune Checkpoint Inhibitors
sharing ipd: No