<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/NCT02252211</url>
  </required_header>
  <id_info>
    <org_study_id>LUD2014-002</org_study_id>
    <nct_id>NCT02252211</nct_id>
  </id_info>
  <brief_title>Safety and Bioimaging Trial of DS-8895a in Patients With Advanced EphA2 Positive Cancers</brief_title>
  <acronym>LUD2014-002</acronym>
  <official_title>A Phase I Safety and Bioimaging Trial of DS-8895a in Patients With Advanced or Metastatic EphA2 Positive Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ludwig Institute for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Daiichi Sankyo Co., Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Austin Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ludwig Institute for Cancer Research</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This was a Phase 1, dose-escalation, non-randomized, open-label, single-center study of&#xD;
      DS-8895a in patients with advanced or metastatic Ephrin type-A receptor 2 (EphA2)-positive&#xD;
      cancers. The primary study objective was to determine the safety of DS-8895a, with secondary&#xD;
      objectives of determining the biodistribution, tumor uptake (bioimaging), pharmacokinetics&#xD;
      (PK), antitumor and pharmacodynamic response, and correlations between pharmacodynamics and&#xD;
      clinical outcomes, as appropriate.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients received an initial ^89Zr trace-labelled infusion of DS-8895a on Day 1, followed by&#xD;
      safety assessments, positron emission tomography (PET) imaging, and PK sampling over a 1-week&#xD;
      period. DS-8895a was infused again on Days 8, 22, and 36. The Day 36 infusion of DS-8895a was&#xD;
      also trace labelled with ^89Zr, with subsequent PET imaging and PK sampling. Four dose levels&#xD;
      (1, 3, 10 and 20 mg/kg) were to be evaluated, with 3 to 6 patients entered at each dose&#xD;
      level. Patients who responded or had stable disease per the Response Evaluation Criteria in&#xD;
      Solid Tumors (RECIST) version 1.1 at the Day 50 restaging may have continued to receive&#xD;
      biweekly treatment with DS-8895a until disease progression, with restaging performed by&#xD;
      computed tomography (CT) scans every 6 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 9, 2014</start_date>
  <completion_date type="Actual">September 8, 2016</completion_date>
  <primary_completion_date type="Actual">September 8, 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>Patients were enrolled in sequential cohorts following a 3+3 dose-escalation scheme.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients With Treatment-emergent Adverse Events</measure>
    <time_frame>Continuously for up to 58 weeks</time_frame>
    <description>Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a</measure>
    <time_frame>Up to Day 43</time_frame>
    <description>The biodistribution and tumor uptake of ^89Zr-Df-DS-8895a was determined based on qualitative analysis of whole body positron emission tomography (PET)/computed tomography (CT) images. PET imaging was performed following the ^89Zr-Df-DS-8895a infusions on Day 1 (Days 1, 4/5, and 7/8) and Day 36 (Days 36, 39/40 and 42/43). Qualitative parameters assessed included tumor uptake of reference lesions (scored on a 0-3 point scale: none, low, med, high). The reference lesions were initially identified on fluorodeoxyglucose (FDG) PET scans with a score of 3 for [18F]-fluorodeoxyglucose uptake. The summary table presents the maximum reference lesion ^89Zr-Df-DS-8895a uptake score reported for individual patients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Best Overall Tumor Response</measure>
    <time_frame>Up to 58 weeks</time_frame>
    <description>Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Screening (up to 21 days before the first dose of study drug), on Day 50, and approximately every 6 weeks thereafter for patients who received continued study dosing. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The pharmacokinetics (PK) of ^89Zr-Df-DS-8895a were calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Total Serum Clearance of DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Maximum Serum Concentration of DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Elimination Half-life of DS-8895a Following the First Infusion</measure>
    <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
    <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Pharmacodynamic (Metabolic) Response</measure>
    <time_frame>Day 29 and Day 50</time_frame>
    <description>The pharmacodynamic (metabolic) response of DS-8895a was assessed by ^18F-FDG PET at Screening, Day 29, and Day 50. Tumor metabolism response was evaluated as the difference in standardized uptake values between the pre- and post-treatment FDG PET scans. The measurement of [18F]-FDG uptake for tumor metabolic response monitoring was performed according to the European Organization for Research and Treatment of Cancer (EORTC) PET response criteria (Young et al. Eur J Cancer 1999;35:1773-82).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Patients With Human Anti-Human Antibody Positivity</measure>
    <time_frame>Up to 43 Weeks</time_frame>
    <description>Blood samples to detect human anti-human antibody (HAHA) formation were collected on Days 1 (pre-infusion [within 7 days of Day 1 dose] and post-infusion), 8, 22, 36 (pre-infusion), and 50 (anytime). For Cycle 2 onward, HAHA samples were collected on Day 1 (pre-infusion) and at the end of the study (anytime). HAHA samples were analyzed using ELISA and were categorized as either positive or negative for a HAHA response. HAHA positivity indicates that a patient has developed an antibody response.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Malignant Solid Tumor</condition>
  <condition>Metastatic EphA2 Positive Cancer</condition>
  <arm_group>
    <arm_group_label>DS-8895a</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients received infusions with DS-8895a on Days 1, 8, 22, and 36. Infusions on Days 1 and 36 were trace labelled with ^89Zr (^89Zr-Df-DS-8895a). The Day 1 dose was 0.2 mg/kg, followed by subsequent doses calculated based on individual patient body weight and dosing cohort assignment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DS-8895a 1 mg/kg</intervention_name>
    <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
    <arm_group_label>DS-8895a</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DS-8895a 3 mg/kg</intervention_name>
    <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
    <arm_group_label>DS-8895a</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DS-8895a 10 mg/kg</intervention_name>
    <description>Patients were to receive infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
    <arm_group_label>DS-8895a</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Advanced or metastatic EphA2 positive cancer (based on immunohistochemistry of&#xD;
             archived or fresh tumor tissue).&#xD;
&#xD;
          2. Malignant tumor that was refractory to standard treatment.&#xD;
&#xD;
          3. At least one reference tumor &gt; 1 cm in size for assessment of tumor uptake of&#xD;
             ^89Zr-Df-DS-8895a.&#xD;
&#xD;
          4. Expected survival of at least 3 months.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group performance status ≤ 1.&#xD;
&#xD;
          6. Within the last week prior to the first study drug administration, laboratory&#xD;
             parameters for vital functions were to be in the normal range. Out-of-range values&#xD;
             that were not clinically significant were permitted, except that the following&#xD;
             parameters were to be in the specified ranges:&#xD;
&#xD;
               -  Neutrophil count ≥ 1.5 x 10^9/L&#xD;
&#xD;
               -  Platelet count ≥ 90 x 10^9/L&#xD;
&#xD;
               -  International normalized ratio ≤ 1.5&#xD;
&#xD;
               -  Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x the upper&#xD;
                  limit of normal (ULN); ≤ 5 x ULN if liver metastases&#xD;
&#xD;
               -  Serum bilirubin ≤ 1.5 x ULN&#xD;
&#xD;
          7. Calculated creatinine clearance ≥ 55 mL/min.&#xD;
&#xD;
          8. Age ≥ 18 years.&#xD;
&#xD;
          9. Able and willing to give valid written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Active central nervous system metastases. Definitively treated metastases were allowed&#xD;
             if stable for 6 weeks off therapy.&#xD;
&#xD;
          2. Known immunodeficiency or human immunodeficiency virus positivity.&#xD;
&#xD;
          3. Serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders,&#xD;
             or any condition that in the opinion of the Investigator would have interfered with&#xD;
             the ability of the patient to fulfill the study requirements.&#xD;
&#xD;
          4. Other malignancy, apart from non-melanoma skin cancer, within 3 years prior to the&#xD;
             first study drug administration that in the opinion of the investigator had &gt; 10% risk&#xD;
             of relapse within 12 months.&#xD;
&#xD;
          5. Significant allergic reaction to prior antibody infusions.&#xD;
&#xD;
          6. Chemotherapy, radiotherapy, or investigational agent within 4 weeks prior to the first&#xD;
             study drug administration.&#xD;
&#xD;
          7. Regular corticosteroid, non-steroidal anti-inflammatory drug (other than paracetamol&#xD;
             or low-dose aspirin) or other immunosuppressive treatment within 3 weeks prior to the&#xD;
             first study drug administration (intermittent dosing permitted if less than 4 doses&#xD;
             within a 3-day period).&#xD;
&#xD;
          8. Mental impairment that could have compromised the ability to give informed consent and&#xD;
             comply with the requirements of the study.&#xD;
&#xD;
          9. Lack of availability for clinical follow-up assessments.&#xD;
&#xD;
         10. Pregnancy or breastfeeding.&#xD;
&#xD;
         11. Women of childbearing potential: Refusal or inability to use effective means of&#xD;
             contraception.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andrew Scott, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Austin Health, Melbourne, Australia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hui Gan, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Austin Health, Melbourne, Australia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>September 22, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <results_first_submitted>February 20, 2018</results_first_submitted>
  <results_first_submitted_qc>October 25, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">March 1, 2019</results_first_posted>
  <last_update_submitted>October 3, 2022</last_update_submitted>
  <last_update_submitted_qc>October 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>EphA2 positive cancer</keyword>
  <keyword>DS-8895a monoclonal antibody</keyword>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>DS-8895a 1 mg/kg</title>
          <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
        </group>
        <group group_id="P2">
          <title>DS-8895a 3 mg/kg</title>
          <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
        </group>
        <group group_id="P3">
          <title>DS-8895a 10 mg/kg</title>
          <description>Patients were to receive infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Dose 1 (Day 1)</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Dose 2 (Day 8)</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Dose 3 (Day 22)</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Dose 4 (Day 36)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Received Further Doses (Through Dose 24)</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive disease</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Serious Adverse Event During Screening</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
      <group_list>
        <group group_id="B1">
          <title>DS-8895a 1 mg/kg</title>
          <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
        </group>
        <group group_id="B2">
          <title>DS-8895a 3 mg/kg</title>
          <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="4"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="67.3" spread="7.4"/>
                    <measurement group_id="B2" value="64.0" spread="15.1"/>
                    <measurement group_id="B3" value="65.9" spread="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.4" spread="4.2"/>
                    <measurement group_id="B2" value="28.1" spread="6.4"/>
                    <measurement group_id="B3" value="26.0" spread="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Treatment-emergent Adverse Events</title>
        <description>Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.</description>
        <time_frame>Continuously for up to 58 weeks</time_frame>
        <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Treatment-emergent Adverse Events</title>
          <description>Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.</description>
          <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum grade 1 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum grade 2 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum grade 5 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment-emergent Serious Adverse Event</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to study withdrawal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a</title>
        <description>The biodistribution and tumor uptake of ^89Zr-Df-DS-8895a was determined based on qualitative analysis of whole body positron emission tomography (PET)/computed tomography (CT) images. PET imaging was performed following the ^89Zr-Df-DS-8895a infusions on Day 1 (Days 1, 4/5, and 7/8) and Day 36 (Days 36, 39/40 and 42/43). Qualitative parameters assessed included tumor uptake of reference lesions (scored on a 0-3 point scale: none, low, med, high). The reference lesions were initially identified on fluorodeoxyglucose (FDG) PET scans with a score of 3 for [18F]-fluorodeoxyglucose uptake. The summary table presents the maximum reference lesion ^89Zr-Df-DS-8895a uptake score reported for individual patients.</description>
        <time_frame>Up to Day 43</time_frame>
        <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a</title>
          <description>The biodistribution and tumor uptake of ^89Zr-Df-DS-8895a was determined based on qualitative analysis of whole body positron emission tomography (PET)/computed tomography (CT) images. PET imaging was performed following the ^89Zr-Df-DS-8895a infusions on Day 1 (Days 1, 4/5, and 7/8) and Day 36 (Days 36, 39/40 and 42/43). Qualitative parameters assessed included tumor uptake of reference lesions (scored on a 0-3 point scale: none, low, med, high). The reference lesions were initially identified on fluorodeoxyglucose (FDG) PET scans with a score of 3 for [18F]-fluorodeoxyglucose uptake. The summary table presents the maximum reference lesion ^89Zr-Df-DS-8895a uptake score reported for individual patients.</description>
          <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Maximum Lesion Uptake Score 0 (No Uptake)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum Lesion Uptake Score 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum Lesion Uptake Score 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Maximum Lesion Uptake Score 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Best Overall Tumor Response</title>
        <description>Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Screening (up to 21 days before the first dose of study drug), on Day 50, and approximately every 6 weeks thereafter for patients who received continued study dosing. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.</description>
        <time_frame>Up to 58 weeks</time_frame>
        <population>The Evaluable Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and completed all study procedures up to Day 50.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Best Overall Tumor Response</title>
          <description>Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Screening (up to 21 days before the first dose of study drug), on Day 50, and approximately every 6 weeks thereafter for patients who received continued study dosing. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.</description>
          <population>The Evaluable Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and completed all study procedures up to Day 50.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stable disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion</title>
        <description>The pharmacokinetics (PK) of ^89Zr-Df-DS-8895a were calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion</title>
          <description>The pharmacokinetics (PK) of ^89Zr-Df-DS-8895a were calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
          <units>hr*μg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="349.0" spread="24.6"/>
                    <measurement group_id="O2" value="486.5" spread="169.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion</title>
        <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion</title>
          <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
          <units>mL/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.3" spread="7.4"/>
                    <measurement group_id="O2" value="51.3" spread="16.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion</title>
        <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion</title>
          <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
          <units>mL/hr/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="0.0"/>
                    <measurement group_id="O2" value="0.5" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion</title>
        <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion</title>
          <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
          <units>µg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="0.4"/>
                    <measurement group_id="O2" value="4.2" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion</title>
        <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion</title>
          <description>The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis.</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.4" spread="5.1"/>
                    <measurement group_id="O2" value="79.9" spread="8.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion</title>
        <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion</title>
          <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
          <units>hr*μg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="255.2" spread="14.5"/>
                    <measurement group_id="O2" value="391.0" spread="190.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion</title>
        <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion</title>
          <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
          <units>mL/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.8" spread="8.7"/>
                    <measurement group_id="O2" value="42.1" spread="11.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Total Serum Clearance of DS-8895a Following the First Infusion</title>
        <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Total Serum Clearance of DS-8895a Following the First Infusion</title>
          <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
          <units>mL/hr/kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.6" spread="0.1"/>
                    <measurement group_id="O2" value="0.5" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Maximum Serum Concentration of DS-8895a Following the First Infusion</title>
        <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Maximum Serum Concentration of DS-8895a Following the First Infusion</title>
          <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
          <units>µg/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="0.3"/>
                    <measurement group_id="O2" value="4.0" spread="1.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Elimination Half-life of DS-8895a Following the First Infusion</title>
        <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
        <time_frame>Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)</time_frame>
        <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Elimination Half-life of DS-8895a Following the First Infusion</title>
          <description>The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.</description>
          <population>The PK Analysis Set comprised all patients who received at least 1 infusion of DS-8895a and had evaluable PK samples for a given analysis. One patient in the 1 mg/kg cohort did not have adequate samples to calculate PK parameters for this analysis.</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.3" spread="9.2"/>
                    <measurement group_id="O2" value="65.3" spread="20.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Pharmacodynamic (Metabolic) Response</title>
        <description>The pharmacodynamic (metabolic) response of DS-8895a was assessed by ^18F-FDG PET at Screening, Day 29, and Day 50. Tumor metabolism response was evaluated as the difference in standardized uptake values between the pre- and post-treatment FDG PET scans. The measurement of [18F]-FDG uptake for tumor metabolic response monitoring was performed according to the European Organization for Research and Treatment of Cancer (EORTC) PET response criteria (Young et al. Eur J Cancer 1999;35:1773-82).</description>
        <time_frame>Day 29 and Day 50</time_frame>
        <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Pharmacodynamic (Metabolic) Response</title>
          <description>The pharmacodynamic (metabolic) response of DS-8895a was assessed by ^18F-FDG PET at Screening, Day 29, and Day 50. Tumor metabolism response was evaluated as the difference in standardized uptake values between the pre- and post-treatment FDG PET scans. The measurement of [18F]-FDG uptake for tumor metabolic response monitoring was performed according to the European Organization for Research and Treatment of Cancer (EORTC) PET response criteria (Young et al. Eur J Cancer 1999;35:1773-82).</description>
          <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Stable Disease at Days 29 and 50</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease at Day 29, Progression at Day 50</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Progressive Disease at Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients With Human Anti-Human Antibody Positivity</title>
        <description>Blood samples to detect human anti-human antibody (HAHA) formation were collected on Days 1 (pre-infusion [within 7 days of Day 1 dose] and post-infusion), 8, 22, 36 (pre-infusion), and 50 (anytime). For Cycle 2 onward, HAHA samples were collected on Day 1 (pre-infusion) and at the end of the study (anytime). HAHA samples were analyzed using ELISA and were categorized as either positive or negative for a HAHA response. HAHA positivity indicates that a patient has developed an antibody response.</description>
        <time_frame>Up to 43 Weeks</time_frame>
        <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
        <group_list>
          <group group_id="O1">
            <title>DS-8895a 1 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
          <group group_id="O2">
            <title>DS-8895a 3 mg/kg</title>
            <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Human Anti-Human Antibody Positivity</title>
          <description>Blood samples to detect human anti-human antibody (HAHA) formation were collected on Days 1 (pre-infusion [within 7 days of Day 1 dose] and post-infusion), 8, 22, 36 (pre-infusion), and 50 (anytime). For Cycle 2 onward, HAHA samples were collected on Day 1 (pre-infusion) and at the end of the study (anytime). HAHA samples were analyzed using ELISA and were categorized as either positive or negative for a HAHA response. HAHA positivity indicates that a patient has developed an antibody response.</description>
          <population>The Safety Analysis Set comprised all patients who received at least 1 infusion of DS-8895a.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
                <count group_id="O2" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Positive HAHA Results (Single Sample)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Negative HAHA Results at all Time Points</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All adverse events (AEs) occurring between the signing of informed consent and the off-study date were documented, regardless of the causal relationship to study drug. AEs occurring after the first dose of study drug were considered treatment emergent (i.e., TEAEs). The AE reporting period for this study was up to 58 weeks.</time_frame>
      <desc>AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 4.0), seriousness, study drug action taken, treatment, and outcome. In summaries, treatment-related AEs included those with a &quot;possible&quot;, &quot;probable&quot;, or &quot;definite&quot; relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.</desc>
      <group_list>
        <group group_id="E1">
          <title>DS-8895a 1 mg/kg</title>
          <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.&#xD;
All enrolled patients are included in AE tabulations; 1 patient was enrolled but discontinued due to SAEs prior to receiving study treatment.</description>
        </group>
        <group group_id="E2">
          <title>DS-8895a 3 mg/kg</title>
          <description>Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.&#xD;
All enrolled patients are included in AE tabulations.</description>
        </group>
        <group group_id="E3">
          <title>DS-8895a 10 mg/kg</title>
          <description>Patients were to have received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.&#xD;
All enrolled patients are included in AE tabulations; 1 patient was enrolled but discontinued due to an SAE prior to receiving study treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Ascites</sub_title>
                <description>Grade 3, not treatment emergent</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <description>Grade 3, not treatment emergent</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasm progression</sub_title>
                <description>Grade 5</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cancer Pain</sub_title>
                <description>Grade 3, not treatment emergent</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Spinal cord compression</sub_title>
                <description>Grade 3</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <description>Grade 5, not treatment emergent</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (15.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rectal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Crepitations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lower respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Thoracic vertebral fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Electrocardiogram abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Dysuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cold sweat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Skin mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jonathan Skipper PhD</name_or_title>
      <organization>Ludwig Institute for Cancer Research</organization>
      <phone>12124501539</phone>
      <email>jskipper@lcr.org</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02252211
org study id: LUD2014-002
nct id: NCT02252211
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This was a Phase 1, dose-escalation, non-randomized, open-label, single-center study of
      DS-8895a in patients with advanced or metastatic Ephrin type-A receptor 2 (EphA2)-positive
      cancers. The primary study objective was to determine the safety of DS-8895a, with secondary
      objectives of determining the biodistribution, tumor uptake (bioimaging), pharmacokinetics
      (PK), antitumor and pharmacodynamic response, and correlations between pharmacodynamics and
      clinical outcomes, as appropriate.
Patients received an initial ^89Zr trace-labelled infusion of DS-8895a on Day 1, followed by
      safety assessments, positron emission tomography (PET) imaging, and PK sampling over a 1-week
      period. DS-8895a was infused again on Days 8, 22, and 36. The Day 36 infusion of DS-8895a was
      also trace labelled with ^89Zr, with subsequent PET imaging and PK sampling. Four dose levels
      (1, 3, 10 and 20 mg/kg) were to be evaluated, with 3 to 6 patients entered at each dose
      level. Patients who responded or had stable disease per the Response Evaluation Criteria in
      Solid Tumors (RECIST) version 1.1 at the Day 50 restaging may have continued to receive
      biweekly treatment with DS-8895a until disease progression, with restaging performed by
      computed tomography (CT) scans every 6 weeks.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: Patients were enrolled in sequential cohorts following a 3+3 dose-escalation scheme.
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Patients With Treatment-emergent Adverse Events
time frame: Continuously for up to 58 weeks
description: Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Treatment-emergent adverse events (TEAEs) were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period.
measure: Number of Patients With Tumor Uptake of ^89Zr-Df-DS-8895a
time frame: Up to Day 43
description: The biodistribution and tumor uptake of ^89Zr-Df-DS-8895a was determined based on qualitative analysis of whole body positron emission tomography (PET)/computed tomography (CT) images. PET imaging was performed following the ^89Zr-Df-DS-8895a infusions on Day 1 (Days 1, 4/5, and 7/8) and Day 36 (Days 36, 39/40 and 42/43). Qualitative parameters assessed included tumor uptake of reference lesions (scored on a 0-3 point scale: none, low, med, high). The reference lesions were initially identified on fluorodeoxyglucose (FDG) PET scans with a score of 3 for [18F]-fluorodeoxyglucose uptake. The summary table presents the maximum reference lesion ^89Zr-Df-DS-8895a uptake score reported for individual patients.
measure: Number of Patients With Best Overall Tumor Response
time frame: Up to 58 weeks
description: Tumor responses were evaluated using computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) at Screening (up to 21 days before the first dose of study drug), on Day 50, and approximately every 6 weeks thereafter for patients who received continued study dosing. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.
measure: Mean Area Under the Serum Concentration Curve of ^89Zr-Df-DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The pharmacokinetics (PK) of ^89Zr-Df-DS-8895a were calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Volume of Distribution at Steady State of ^89Zr-Df-DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Total Serum Clearance of ^89Zr-Df-DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Maximum Serum Concentration of ^89Zr-Df-DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Elimination Half-life of ^89Zr-Df-DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of ^89Zr-Df-DS-8895a was calculated based on data from gamma counting of serum samples. Serum samples for gamma counting were drawn on Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion), Day 2 (24 hours post-infusion), Day 4/5 (anytime), Day 36 (pre-infusion, and 5 minutes, 1, 2, and 4 hours post infusion), Day 37 (24 hours post-infusion), Day 39/40 (anytime), Day 42/43 (anytime), and Day 50 (anytime). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Area Under the Serum Concentration Curve of DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Volume of Distribution at Steady State of DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Total Serum Clearance of DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Maximum Serum Concentration of DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Mean Elimination Half-life of DS-8895a Following the First Infusion
time frame: Cycle 1 Day 1 (pre-infusion and 5 minutes, 1, 2, and 4 hours post-infusion)
description: The PK of DS-8895a was calculated based on data from enzyme-linked immunosorbent assay (ELISA) of serum samples. Serum samples for ELISA were drawn at the same times as for gamma counting with the addition of Day 8 (pre- and 0 to 30 minutes post-infusion), Day 9 (anytime), and Day 22 (pre- and 0 to 30 minutes post-infusion). For Cycle 2 onward, blood samples for PK were taken at pre- and 0 to 30 minutes post-infusion on Days 1, 15, and 29.
measure: Number of Patients With Pharmacodynamic (Metabolic) Response
time frame: Day 29 and Day 50
description: The pharmacodynamic (metabolic) response of DS-8895a was assessed by ^18F-FDG PET at Screening, Day 29, and Day 50. Tumor metabolism response was evaluated as the difference in standardized uptake values between the pre- and post-treatment FDG PET scans. The measurement of [18F]-FDG uptake for tumor metabolic response monitoring was performed according to the European Organization for Research and Treatment of Cancer (EORTC) PET response criteria (Young et al. Eur J Cancer 1999;35:1773-82).
measure: Number of Patients With Human Anti-Human Antibody Positivity
time frame: Up to 43 Weeks
description: Blood samples to detect human anti-human antibody (HAHA) formation were collected on Days 1 (pre-infusion [within 7 days of Day 1 dose] and post-infusion), 8, 22, 36 (pre-infusion), and 50 (anytime). For Cycle 2 onward, HAHA samples were collected on Day 1 (pre-infusion) and at the end of the study (anytime). HAHA samples were analyzed using ELISA and were categorized as either positive or negative for a HAHA response. HAHA positivity indicates that a patient has developed an antibody response.
arm group label: DS-8895a
arm group type: Experimental
description: Patients received infusions with DS-8895a on Days 1, 8, 22, and 36. Infusions on Days 1 and 36 were trace labelled with ^89Zr (^89Zr-Df-DS-8895a). The Day 1 dose was 0.2 mg/kg, followed by subsequent doses calculated based on individual patient body weight and dosing cohort assignment.
intervention type: Drug
intervention name: DS-8895a 1 mg/kg
description: Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 1 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 1 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.
arm group label: DS-8895a
intervention type: Drug
intervention name: DS-8895a 3 mg/kg
description: Patients received infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 3 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 3 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.
arm group label: DS-8895a
intervention type: Drug
intervention name: DS-8895a 10 mg/kg
description: Patients were to receive infusions with ^89Zr-Df-DS-8895a at a dose of 0.2 mg/kg on Day 1, DS-8895a at a dose of 10 mg/kg on Days 8 and 22, and ^89Zr-Df-DS-8895a at a dose of 10 mg/kg on Day 36. Patients who responded or had stable disease per RECIST version 1.1 at the Day 50 restaging may have continued to receive biweekly treatment with DS-8895a until disease progression.
arm group label: DS-8895a
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew Scott, MD
role: Principal Investigator
affiliation: Austin Health, Melbourne, Australia
last name: Hui Gan, MD, PhD
role: Principal Investigator
affiliation: Austin Health, Melbourne, Australia
facility: 
country: Australia
responsible party type: Sponsor
sharing ipd: Undecided
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 