<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/NCT04479436</url>
  </required_header>
  <id_info>
    <org_study_id>U31402-A-U202</org_study_id>
    <secondary_id>2019-004418-32</secondary_id>
    <nct_id>NCT04479436</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer</brief_title>
  <official_title>A Multi-Center, Open-Label, Phase 2 Study to Evaluate Safety and Efficacy of U3-1402 in Subjects With Advanced or Metastatic Colorectal Cancer (CRC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Daiichi Sankyo, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to primarily evaluate the safety and efficacy of U3-1402 in&#xD;
      participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2&#xD;
      prior lines of therapy and will explore clinical benefit according to human epidermal growth&#xD;
      factor receptor 3 (HER3) tumor expression level in otherwise refractory tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There will be 2 cohorts with enrollment in 2 parts. Participants will be treated on Day 1 of&#xD;
      each 21-day cycle (every 3 weeks) with U3-1402 5.6 mg/kg intravenous (IV). The estimated&#xD;
      treatment period is approximately 8 months and the follow-up period is approximately 4&#xD;
      months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was terminated early given the Interim Analysis for Part 1 (signal finding) did not meet&#xD;
    pre-specified criteria and will not proceed to Part 2. Sponsor will proceed closing the study.&#xD;
  </why_stopped>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Actual">February 3, 2022</completion_date>
  <primary_completion_date type="Actual">February 3, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months</time_frame>
    <description>ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months</time_frame>
    <description>DOR defined as the time from the first documented response (CR or PR) to the date of disease progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline up to disease progression, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months</time_frame>
    <description>ORR defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by Investigator.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR) As Assessed by Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline up to disease progression, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months</time_frame>
    <description>DoR defined as the time from the first documented response (complete response [CR] or partial response [PR]) to the date of disease progression or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months</time_frame>
    <description>DCR is defined as the proportion of participants who achieved a confirmed best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) as assessed by blinded independent central review or by the Investigator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months</time_frame>
    <description>TTR defined as the time from the start of study treatment to the date of the first documentation of objective response (complete response [CR] or partial response [PR]) that is subsequently confirmed by Blinded Independent Central Review or by the Investigator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline until disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), assessed up to 27 months</time_frame>
    <description>PFS is defined as the time from the start of study treatment to the date of the first documentation of objective PD or death due to any cause, whichever is earlier</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>From baseline up to the date of death due to any cause or 27 months, whichever is earlier.</time_frame>
    <description>OS defined as the time from the start of study treatment to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Reported Treatment-emergent Adverse Events (TEAEs) and other safe parameters during the study</measure>
    <time_frame>From baseline up to Day 40 post last dose, approximately 27 months</time_frame>
    <description>Incidence of TEAEs, serious adverse events, adverse events of special interests (interstitial lung disease; and elevation of aminotransferases and total bilirubin), Eastern Cooperative Oncology Group performance status, vital sign measurements, standard clinical laboratory parameters will be assessed</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)</measure>
    <time_frame>From baseline up to 3 months post end of treatment, up to approximately 27 months</time_frame>
    <description>The immunogenicity of U3-1402 will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants Who Have Treatment-emergent ADA</measure>
    <time_frame>From baseline up to 3 months post end of treatment, up to approximately 27 months</time_frame>
    <description>The immunogenicity of U3-1402 will be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic (PK) of Maximum Serum Concentration (Cmax) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)</time_frame>
    <description>Plasma concentrations at each time point and PK parameters Cmax of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic of Time to Reach Maximum Serum Concentration (Tmax) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)</time_frame>
    <description>Plasma concentrations at each time point and PK parameters Tmax of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic of Trough Serum Concentration (Ctrough) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)</time_frame>
    <description>Plasma concentrations at each time point and PK parameters Ctrough of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer</measure>
    <time_frame>At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)</time_frame>
    <description>Plasma concentrations at each time point and PK parameters AUClast and AUCtau of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Metastatic Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort 1: HER3 High (IHC 3+, 2+)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 1 participants will have high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: HER3 Low/Negative (IHC 1+, 0)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cohort 2 participants will have low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels in a pre-treatment biopsy specimen.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Patritumab Deruxtecan</intervention_name>
    <description>U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.</description>
    <arm_group_label>Cohort 1: HER3 High (IHC 3+, 2+)</arm_group_label>
    <arm_group_label>Cohort 2: HER3 Low/Negative (IHC 1+, 0)</arm_group_label>
    <other_name>U3-1402</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant has provided written informed consent prior to the start of any study&#xD;
             specific procedures.&#xD;
&#xD;
          -  Participants ≥18 years (follow local regulatory requirements if the legal age of&#xD;
             consent for study participation is &gt;18 years old).&#xD;
&#xD;
          -  Pathological/histological confirmation of advanced or metastatic colon or rectal&#xD;
             adenocarcinoma.&#xD;
&#xD;
          -  Must be resistant, refractory, or intolerant to at least 2 prior lines of systemic&#xD;
             therapy, that must include all of the following agents:&#xD;
&#xD;
               -  Fluoropyrimidine&#xD;
&#xD;
               -  Irinotecan&#xD;
&#xD;
               -  Platinum agents (e.g, oxaliplatin)&#xD;
&#xD;
               -  An anti-epidermal growth factor receptor (EGFR) agent, if clinically indicated&#xD;
&#xD;
               -  An anti-VEGF agent, if clinically indicated (eg, bevacizumab)&#xD;
&#xD;
               -  An immune checkpoint inhibitor (eg, microsatellite instability-high [MSI-H]&#xD;
                  status)&#xD;
&#xD;
               -  A BRAF inhibitor, if clinically indicated (eg, BRAF V600E positive)&#xD;
&#xD;
          -  Has at least 1 measurable lesion confirmed by blinded independent central review&#xD;
             (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1.&#xD;
&#xD;
          -  Willing to provide a required pre-treatment tumor biopsy and an additional archival&#xD;
             tissue sample for the assessment of HER3 expression levels by immunohistochemistry and&#xD;
             exploratory biomarkers, defined as:&#xD;
&#xD;
               1. Pre-treatment tumor biopsy. Participants may be exempted from the requirement to&#xD;
                  provide a pre-treatment tumor biopsy if archival tumor tissue was collected&#xD;
                  within 3 months of screening during or after treatment with the last prior cancer&#xD;
                  treatment and is of sufficient quantity (2 cores or 20 slides with adequate tumor&#xD;
                  tissue content).&#xD;
&#xD;
               2. An additional archival tissue sample collected greater than 3 months prior to&#xD;
                  screening must be available and of sufficient quantity, as defined above, at the&#xD;
                  time of screening. If an archival tissue sample (collected greater than 3 months&#xD;
                  prior to screening) is not available, a subject may be included provided the&#xD;
                  pre-treatment tumor biopsy is obtained and after discussion and agreement from&#xD;
                  Sponsor (Medical Monitor or designee).&#xD;
&#xD;
               3. Consent to provide on-treatment tumor biopsy. When at least 10 treatment tumor&#xD;
                  biopsies have been collected, the Sponsor will provide written notification of a&#xD;
                  change to the requirement.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.&#xD;
&#xD;
          -  Life expectancy ≥3 months.&#xD;
&#xD;
          -  Has adequate bone marrow reserve and organ function at baseline based on local&#xD;
             laboratory data defined as follows within 14 days prior to Cycle 1 Day 1:&#xD;
&#xD;
               -  Platelet count: ≥100,000/mm^3 or ≥100 × 10^9/L (platelet transfusions are not&#xD;
                  allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)&#xD;
&#xD;
               -  Hemoglobin: ≥9.0 g/dL (transfusion and/or growth factor support is allowed)&#xD;
&#xD;
               -  Absolute neutrophil count: ≥1500/mm^3 or ≥1.5 × 10^9/L&#xD;
&#xD;
               -  Serum creatinine (SCr) OR creatinine clearance (CrCl): SCr ≤ 1.5 × upper limit of&#xD;
                  normal (ULN), OR CrCl ≥ 30 mL/min as calculated using the Cockcroft- Gault&#xD;
                  equation or measured CrCl; confirmation of CrCl is only required when creatinine&#xD;
                  is &gt;1.5 × ULN&#xD;
&#xD;
               -  Alanine aminotransferase /aspartate aminotransferase: ≤3 × ULN (if liver&#xD;
                  metastases are present, ≤5 × ULN)&#xD;
&#xD;
               -  Total bilirubin: ≤1.5 × ULN if no liver metastases (&lt;3 × ULN in the presence of&#xD;
                  documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver&#xD;
                  metastases)&#xD;
&#xD;
               -  Serum albumin: ≥2.5 g/dL&#xD;
&#xD;
               -  Prothrombin time (PT) or PT-international normalized ratio (INR) and activated&#xD;
                  partial thromboplastin time (aPTT) / partial thromboplastin time (PTT): ≤1.5 ×&#xD;
                  ULN except for subjects on coumarin- derivative anticoagulants or other similar&#xD;
                  anticoagulant therapy, who must have PT-INR within therapeutic range as deemed&#xD;
                  appropriate by the Investigator&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any history of interstitial lung disease (including pulmonary fibrosis or radiation&#xD;
             pneumonitis), has current interstitial lung disease (ILD), or is suspected to have&#xD;
             such disease by imaging during screening.&#xD;
&#xD;
          -  Clinically severe pulmonary compromise (based on Investigator's assessment) resulting&#xD;
             from intercurrent pulmonary illnesses including, but not limited to:&#xD;
&#xD;
               1. any underlying pulmonary disorder (e.g., pulmonary emboli, severe asthma, severe&#xD;
                  chronic obstructive pulmonary disease, restrictive lung disease, pleural&#xD;
                  effusion)&#xD;
&#xD;
               2. any autoimmune, connective tissue or inflammatory disorder with pulmonary&#xD;
                  involvement (eg, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis)&#xD;
&#xD;
                    -  OR prior complete pneumonectomy.&#xD;
&#xD;
          -  Is receiving chronic systemic corticosteroids dosed at &gt;10 mg prednisone or equivalent&#xD;
             anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1&#xD;
             Day 1. Participants who require use of bronchodilators, inhaled or topical steroids,&#xD;
             or local steroid injections may be included in the study.&#xD;
&#xD;
          -  Evidence of leptomeningeal disease.&#xD;
&#xD;
          -  Evidence of clinically active spinal cord compression or brain metastases&#xD;
&#xD;
          -  Inadequate washout period prior to Cycle 1 Day 1 of U3-1402:&#xD;
&#xD;
               1. Whole brain radiation therapy &lt;14 days or stereotactic brain radiation therapy &lt;7&#xD;
                  days;&#xD;
&#xD;
               2. Any cytotoxic chemotherapy, investigational agent or other anticancer drug(s)&#xD;
                  from a previous cancer treatment regimen or clinical study &lt;14 days or 5&#xD;
                  half-lives, whichever is longer;&#xD;
&#xD;
               3. Monoclonal antibodies other than immune checkpoint inhibitors, such as&#xD;
                  bevacizumab (anti-VEGF) and cetuximab (anti-EGFRs) &lt;28 days;&#xD;
&#xD;
               4. Immune checkpoint inhibitor therapy &lt;21 days;&#xD;
&#xD;
               5. Major surgery (excluding placement of vascular access) &lt;4 weeks;&#xD;
&#xD;
               6. Radiotherapy treatment to &gt;30% of the bone marrow or with a wide field of&#xD;
                  radiation &lt;28 days or palliative radiation therapy &lt;14 days;&#xD;
&#xD;
               7. Chloroquine/hydroxychloroquine ≤14 days.&#xD;
&#xD;
          -  Prior treatment with an anti-HER3 antibody and/or antibody drug conjugate (ADC) that&#xD;
             consists of an exatecan derivative that is any topoisomerase I inhibitor (e.g,&#xD;
             trastuzumab deruxtecan).&#xD;
&#xD;
          -  Has unresolved toxicities from previous anticancer therapy, defined as toxicities&#xD;
             (other than alopecia) not yet resolved to National Cancer Institute Common Terminology&#xD;
             Criteria for Adverse Events (NCI-CTCAE) v5.0 Grade ≤1 or baseline.&#xD;
&#xD;
          -  Had primary malignancies other than CRC within 3 years prior to Cycle 1 Day 1, except&#xD;
             adequately resected non-melanoma skin cancer, curatively treated in-situ disease, or&#xD;
             other solid tumors curatively treated.&#xD;
&#xD;
          -  Uncontrolled or significant cardiovascular disease prior to Cycle 1 Day 1.&#xD;
&#xD;
          -  Known Hepatitis B and/or Hepatitis C infection, such as those with serologic evidence&#xD;
             of viral infection within 28 days of Cycle 1 Day 1.&#xD;
&#xD;
               1. Participants with past or resolved hepatitis B virus (HBV) infection are eligible&#xD;
                  if:&#xD;
&#xD;
                    -  Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody&#xD;
                       (anti-HBc) positive; OR&#xD;
&#xD;
                    -  HBsAg positive and HBV deoxyribonucleic acid (DNA) viral load is documented&#xD;
                       to be ≤2000 IU/mL in the absence of anti-viral therapy and during the&#xD;
                       previous 12 weeks prior to the viral load evaluation with normal&#xD;
                       transaminases values (in the absence of liver metastasis); OR&#xD;
&#xD;
                    -  HBsAg positive and HBV DNA viral load is documented to be ≤2000 IU/mL in the&#xD;
                       absence of anti-viral therapy and during the previous 12 weeks prior to the&#xD;
                       viral load evaluation for participants with liver metastasis and abnormal&#xD;
                       transaminases with a result of AST/ALT &lt;3 × ULN.&#xD;
&#xD;
               2. Participants with a history of hepatitis C infection will be eligible for&#xD;
                  enrollment only if the viral load according to local standards of detection is&#xD;
                  documented to be below the level of detection in the absence of anti-viral&#xD;
                  therapy during the previous 12 weeks (ie, sustained viral response according to&#xD;
                  the local product label but no less than 12 weeks, whichever is longer).&#xD;
&#xD;
          -  Participant with any human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
          -  Any evidence of severe or uncontrolled systemic diseases (including active bleeding&#xD;
             diatheses, active infection), psychiatric illness/social situations, geographical&#xD;
             factors, substance abuse, or other factors which in the Investigator's opinion makes&#xD;
             it undesirable for the participant to participate in the study or which would&#xD;
             jeopardize compliance with the protocol. Screening for chronic conditions is not&#xD;
             required.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Leader</last_name>
    <role>Study Director</role>
    <affiliation>Daiichi Sankyo, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Highlands Oncology</name>
      <address>
        <city>Fayetteville</city>
        <state>Arkansas</state>
        <zip>72703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>City of Hope Comprehensive Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern Medical Faculty Foundation NMFF Hematology Oncology</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Hopkins Sidney Kimmel Comprehensive Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nebraska Cancer Specialists</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Cancer Center</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Cancer Research</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center University of Texas</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Utah Cancer Specialists</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Virgina Cancer Specialists</name>
      <address>
        <city>Fairfax</city>
        <state>Virginia</state>
        <zip>22031</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Antwerpen</name>
      <address>
        <city>Edegem</city>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Georges-Franois Leclerc</name>
      <address>
        <city>Dijon</city>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes</name>
      <address>
        <city>Nantes</city>
        <zip>44000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital St Antoine</name>
      <address>
        <city>Paris</city>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asst Grande Ospedale Metropolitano Niguarda</name>
      <address>
        <city>Milano</city>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aichi Cancer Center Hospital</name>
      <address>
        <city>Nagoya-shi</city>
        <state>Nagoya-shi, Aichi-ken</state>
        <zip>464-8681</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Hospital Organization - Osaka National Hospital (ONH)</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka-shi, Osaka-fu</state>
        <zip>540-0006</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital</name>
      <address>
        <city>Osaka</city>
        <state>Osakasayama Shi</state>
        <zip>589-8511</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Chiba</city>
        <zip>277-0023</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cancer Institute Hospital Of JFCR</name>
      <address>
        <city>Tokyo</city>
        <zip>135-8550</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego w Poznaniu</name>
      <address>
        <city>Ostrów Wielkopolski</city>
        <state>Poznan</state>
        <zip>60-569</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szpital Kliniczny Przemienienia Pańskiego.University Hospital, Chemotherapy Department</name>
      <address>
        <city>Poznań</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M Sklodowska Curie Memorial Cancer Center</name>
      <address>
        <city>Warszawa</city>
        <zip>02-034</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M Sklodowska Curie Memorial Cancer Center</name>
      <address>
        <city>Warszawa</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar - Institut Hospital del Mar d'Investigacions Mediques IMIM</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VHIO Valle de Hebron Instituto de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario La Paz</name>
      <address>
        <city>Madrid</city>
        <zip>28046</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario HM Sanchinarro, CIOCC</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Consorci Corporació Sanitària Parc Taulí de Sabadell</name>
      <address>
        <city>Sabadell</city>
        <zip>08208</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital NHS</name>
      <address>
        <city>London</city>
        <zip>SW3 6JJ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute UK</name>
      <address>
        <city>London</city>
        <zip>W1G 6AD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital NHS</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Italy</country>
    <country>Japan</country>
    <country>Poland</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 21, 2020</study_first_posted>
  <disposition_first_submitted>January 10, 2023</disposition_first_submitted>
  <disposition_first_submitted_qc>January 10, 2023</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 13, 2023</disposition_first_posted>
  <last_update_submitted>January 10, 2023</last_update_submitted>
  <last_update_submitted_qc>January 10, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic Colorectal Cancer</keyword>
  <keyword>U3-1402</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Patritumab deruxtecan</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/daiichi-sankyo/</ipd_url>
  </patient_data>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04479436
org study id: U31402-A-U202
secondary id: 2019-004418-32
nct id: NCT04479436
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is designed to primarily evaluate the safety and efficacy of U3-1402 in
      participants with advanced or metastatic colorectal cancer (CRC) who have received at least 2
      prior lines of therapy and will explore clinical benefit according to human epidermal growth
      factor receptor 3 (HER3) tumor expression level in otherwise refractory tumors.
There will be 2 cohorts with enrollment in 2 parts. Participants will be treated on Day 1 of
      each 21-day cycle (every 3 weeks) with U3-1402 5.6 mg/kg intravenous (IV). The estimated
      treatment period is approximately 8 months and the follow-up period is approximately 4
      months.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective Response Rate (ORR) As Assessed By Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months
description: ORR defined as the proportion of participants with a best overall response of confirmed complete response (CR) or partial response (PR) as assessed by blinded independent central review.
measure: Duration of Response (DOR) As Assessed by Blinded Independent Central Review (BICR) Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months
description: DOR defined as the time from the first documented response (CR or PR) to the date of disease progression or death due to any cause.
measure: Objective Response Rate (ORR) As Assessed by Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline up to disease progression, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months
description: ORR defined as the proportion of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) as assessed by Investigator.
measure: Duration of Response (DoR) As Assessed by Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline up to disease progression, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months
description: DoR defined as the time from the first documented response (complete response [CR] or partial response [PR]) to the date of disease progression or death due to any cause.
measure: Disease Control Rate (DCR) by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months
description: DCR is defined as the proportion of participants who achieved a confirmed best overall response (BOR) of complete response (CR), partial response (PR), or stable disease (SD) as assessed by blinded independent central review or by the Investigator
measure: Time to Tumor Response (TTR) As Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline up to disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), up to approximately 27 months
description: TTR defined as the time from the start of study treatment to the date of the first documentation of objective response (complete response [CR] or partial response [PR]) that is subsequently confirmed by Blinded Independent Central Review or by the Investigator
measure: Progression-free Survival (PFS) Assessed by Blinded Independent Central Review (BICR) and Investigator Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline until disease progression by BICR, death, lost to follow up, or withdrawal of consent by subject (whichever occurs first), assessed up to 27 months
description: PFS is defined as the time from the start of study treatment to the date of the first documentation of objective PD or death due to any cause, whichever is earlier
measure: Overall Survival (OS) Following Administration of U3-1402 In Participants with Advanced or Metastatic Colorectal Cancer
time frame: From baseline up to the date of death due to any cause or 27 months, whichever is earlier.
description: OS defined as the time from the start of study treatment to the date of death due to any cause.
measure: Summary of Reported Treatment-emergent Adverse Events (TEAEs) and other safe parameters during the study
time frame: From baseline up to Day 40 post last dose, approximately 27 months
description: Incidence of TEAEs, serious adverse events, adverse events of special interests (interstitial lung disease; and elevation of aminotransferases and total bilirubin), Eastern Cooperative Oncology Group performance status, vital sign measurements, standard clinical laboratory parameters will be assessed
measure: Proportion of Participants Who Are Anti-Drug Antibody (ADA)-Positive (Baseline and Post-Baseline)
time frame: From baseline up to 3 months post end of treatment, up to approximately 27 months
description: The immunogenicity of U3-1402 will be assessed.
measure: Proportion of Participants Who Have Treatment-emergent ADA
time frame: From baseline up to 3 months post end of treatment, up to approximately 27 months
description: The immunogenicity of U3-1402 will be assessed.
measure: Pharmacokinetic (PK) of Maximum Serum Concentration (Cmax) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer
time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)
description: Plasma concentrations at each time point and PK parameters Cmax of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort
measure: Pharmacokinetic of Time to Reach Maximum Serum Concentration (Tmax) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer
time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)
description: Plasma concentrations at each time point and PK parameters Tmax of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort
measure: Pharmacokinetic of Trough Serum Concentration (Ctrough) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer
time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)
description: Plasma concentrations at each time point and PK parameters Ctrough of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort
measure: Pharmacokinetic of Area Under the Serum Concentration-Time Curve Up to Last Quantifiable Time (AUClast) and During Dosing Interval (AUCtau) of analytes of U3-1402 Following Administration In Participants with Advanced or Metastatic Colorectal Cancer
time frame: At baseline (-8 hour to 0 hour), pre-infusion, and 15 minutes, 1 hour, 2 hour, 4 hour, and 8 hour post-infusion of Cycle 1 through Cycle 8 (each cycle is 21 days)
description: Plasma concentrations at each time point and PK parameters AUClast and AUCtau of U3-1402 (ADC, total anti-HE antibody, and MAAA-1181a) will be assessed in the full PK sampling cohort
arm group label: Cohort 1: HER3 High (IHC 3+, 2+)
arm group type: Experimental
description: Cohort 1 participants will have high tumor expression levels of human epidermal receptor 3 (HER3) in a pre-treatment biopsy specimen.
arm group label: Cohort 2: HER3 Low/Negative (IHC 1+, 0)
arm group type: Experimental
description: Cohort 2 participants will have low or negative tumor expression levels of human epidermal receptor 3 (HER3) expression levels in a pre-treatment biopsy specimen.
intervention type: Drug
intervention name: Patritumab Deruxtecan
description: U3-1402 will be dosed at 5.6 mg/kg as an intravenous (IV) infusion administered on Day 1 of each 21-day cycle.
arm group label: Cohort 1: HER3 High (IHC 3+, 2+)
arm group label: Cohort 2: HER3 Low/Negative (IHC 1+, 0)
other name: U3-1402
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Global Clinical Leader
role: Study Director
affiliation: Daiichi Sankyo, Inc.
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country: Belgium
country: France
country: Italy
country: Japan
country: Poland
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Patritumab deruxtecan
sharing ipd: Yes
ipd description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
ipd access criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
ipd url: https://vivli.org/ourmember/daiichi-sankyo/