<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/NCT03043313</url>
  </required_header>
  <id_info>
    <org_study_id>SGNTUC-017</org_study_id>
    <secondary_id>NCI-2017-01107</secondary_id>
    <secondary_id>ACCRU-GI-1617</secondary_id>
    <secondary_id>P30CA015083</secondary_id>
    <nct_id>NCT03043313</nct_id>
  </id_info>
  <brief_title>Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer</brief_title>
  <official_title>MOUNTAINEER: A Phase II, Open Label Study of Tucatinib Combined With Trastuzumab in Patients With HER2+ Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seagen Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Academic and Community Cancer Research United</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Seagen Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial studies how well the drug tucatinib works when given with trastuzumab and when&#xD;
      given by itself. The participants in this trial have HER2-positive (HER2+) metastatic&#xD;
      colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the&#xD;
      body.&#xD;
&#xD;
      In the first part of this study, participants enrolled into Cohort A and received both&#xD;
      tucatinib and trastuzumab. In the second part of this study, participants are randomly&#xD;
      assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and&#xD;
      trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do&#xD;
      not respond to therapy may have an option to receive tucatinib plus trastuzumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 23, 2017</start_date>
  <completion_date type="Anticipated">September 30, 2023</completion_date>
  <primary_completion_date type="Actual">March 28, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Confirmed Objective Response Rate (cORR) Per RECIST 1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B</measure>
    <time_frame>Up to 46.6 months</time_frame>
    <description>cORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>ORR by 12 Weeks of Treatment Per RECIST 1.1 According to BICR Assessment</measure>
    <time_frame>Up to 3 months</time_frame>
    <description>ORR per BICR by 12 Weeks is defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) Per RECIST 1.1 According to BICR Assessment</measure>
    <time_frame>Up to 44.7 months</time_frame>
    <description>DOR is defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) Per RECIST 1.1 According to BICR Assessment for Pooled Cohorts A+B</measure>
    <time_frame>Up to 46.6 months</time_frame>
    <description>PFS is defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST 1.1) or death from any cause, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) in Pooled Cohorts A+B</measure>
    <time_frame>Up to 53 months</time_frame>
    <description>OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (AEs)</measure>
    <time_frame>Up to 49.3 months</time_frame>
    <description>An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With AEs Resulting in Dose Modification</measure>
    <time_frame>Up to 49.3 months</time_frame>
    <description>Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)</measure>
    <time_frame>Up to 49.3 months</time_frame>
    <description>Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry)</measure>
    <time_frame>Up to 49.3 months</time_frame>
    <description>Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">117</enrollment>
  <condition>Metastatic Colorectal Adenocarcinoma</condition>
  <arm_group>
    <arm_group_label>Cohort A: Tucatinib + Trastuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B: Tucatinib + Trastuzumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C: Tucatinib Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Trastuzumab</intervention_name>
    <description>Given intravenously (into the vein; IV)</description>
    <arm_group_label>Cohort A: Tucatinib + Trastuzumab</arm_group_label>
    <arm_group_label>Cohort B: Tucatinib + Trastuzumab</arm_group_label>
    <other_name>Herceptin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tucatinib</intervention_name>
    <description>Given orally</description>
    <arm_group_label>Cohort A: Tucatinib + Trastuzumab</arm_group_label>
    <arm_group_label>Cohort B: Tucatinib + Trastuzumab</arm_group_label>
    <arm_group_label>Cohort C: Tucatinib Monotherapy</arm_group_label>
    <other_name>ARRY-380</other_name>
    <other_name>ONT-380</other_name>
    <other_name>TUKYSA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Histologically and/or cytologically documented adenocarcinoma of the colon or rectum&#xD;
             that is metastatic and/or unresectable&#xD;
&#xD;
          -  Unless contraindicated, participants must have received and failed regimens containing&#xD;
             the following agents: fluoropyrimidine (e.g., 5-fluorouracil or capecitabine),&#xD;
             oxaliplatin, irinotecan, an anti-VEGF monoclonal antibody (bevacizumab, ramucirumab,&#xD;
             or ziv-aflibercept), and an anti-PD-(L)1 therapy (nivolumab or pembrolizumab) if tumor&#xD;
             has deficient mismatch repair proteins or is MSI-High.&#xD;
&#xD;
          -  Have progression of unresectable or metastatic CRC after the last systemic therapy, or&#xD;
             be intolerant of last systemic therapy&#xD;
&#xD;
          -  Have RAS wild-type in primary or metastatic tumor tissue, based on expanded RAS&#xD;
             testing&#xD;
&#xD;
          -  Willing and able to provide the most recently available tissue blocks obtained prior&#xD;
             to treatment initiation. If archival tissue is not available, then a newly-obtained&#xD;
             baseline biopsy of an accessible tumor&#xD;
&#xD;
          -  Have confirmed HER2-positive mCRC, as defined by having tumor tissue tested at a&#xD;
             Clinical Laboratory Improvement Act (CLIA)-certified or International Organization for&#xD;
             Standardization (ISO)-accredited laboratory, meeting at least one of the following&#xD;
             criteria:&#xD;
&#xD;
               -  HER2+ overexpression (3+ immunohistochemistry [IHC]) by an FDA-approved or&#xD;
                  Conformité Européene (CE)-marked HER2 ICH test&#xD;
&#xD;
               -  HER2 2+ IHC is eligible if the tumor is amplified by an FDA-approved or CE-marked&#xD;
                  HER2 in situ hybridization assay (FISH or chromogenic in situ hybridization&#xD;
                  [CISH]))&#xD;
&#xD;
               -  HER2 (ERBB2) amplification by CLIA-certified or ISO-accredited next generation&#xD;
                  sequencing (NGS) sequencing assay&#xD;
&#xD;
          -  Have radiographically measurable disease assessable by RECIST 1.1, with at least one&#xD;
             site of disease that is measurable and that has not been previously irradiated; or, if&#xD;
             the participant has had previous radiation to the target lesion(s), there must be&#xD;
             evidence of progression since the radiation&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2&#xD;
&#xD;
          -  Life expectancy greater than 3 months&#xD;
&#xD;
          -  Have adequate hematological, hepatic, renal, coagulation, and cardiac function&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Previous treatment with anti-HER2 targeting therapy&#xD;
&#xD;
          -  Previous treatment with any systemic anticancer therapy, non-central nervous system&#xD;
             radiation, or experimental agent within 3 weeks of first dose of study treatment&#xD;
&#xD;
          -  Toxicity related to prior cancer therapies that has not resolved to ≤ Grade 1, with&#xD;
             the following exceptions:&#xD;
&#xD;
               -  Alopecia and neuropathy, which must have resolved to ≤ Grade 2&#xD;
&#xD;
               -  Congestive heart failure (CHF), which must have been ≤ Grade 1 in severity at the&#xD;
                  time of occurrence, and must have resolved completely&#xD;
&#xD;
               -  Anemia, which must have resolved to ≤ Grade 2&#xD;
&#xD;
               -  Decreased ANC, which must have resolved to ≤ Grade 2&#xD;
&#xD;
          -  Have clinically significant cardiopulmonary disease&#xD;
&#xD;
          -  Have known myocardial infarction, unstable angina, cardiac or other vascular stenting,&#xD;
             angioplasty, or cardiac surgery within 6 months prior to first dose of study treatment&#xD;
&#xD;
          -  Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior&#xD;
             to enrollment (≤56 days for hepatectomy, open thoracotomy, or major neurosurgery) or&#xD;
             anticipation of need for major surgical procedure during the study&#xD;
&#xD;
          -  Serious, non-healing wound, ulcer, or bone fracture&#xD;
&#xD;
          -  Known to be positive for hepatitis B by surface antigen expression&#xD;
&#xD;
          -  Known to have active hepatitis C infection&#xD;
&#xD;
               -  Exception for participants with a documented sustained virologic response of 12&#xD;
                  weeks&#xD;
&#xD;
          -  Known to be positive for human immunodeficiency virus (HIV)&#xD;
&#xD;
          -  Subjects who are pregnant, breastfeeding, or planning a pregnancy&#xD;
&#xD;
          -  Inability to swallow pills or any significant gastrointestinal disease which would&#xD;
             preclude the adequate oral absorption of medications&#xD;
&#xD;
          -  Have used strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or have used a&#xD;
             strong CYP2C8 or CYP3A4 inducer within 5 days prior to first dose of study treatment&#xD;
&#xD;
          -  History of another malignancy within 3 years before the first dose of study drug, or&#xD;
             any evidence of residual disease from a previously diagnosed malignancy.&#xD;
&#xD;
               -  Exceptions are malignancies with a negligible risk of metastasis or death&#xD;
&#xD;
          -  Subjects with known active CNS metastasis&#xD;
&#xD;
               -  Irradiated or resected lesions are permitted, provided the lesions are fully&#xD;
                  treated and inactive, subject is asymptomatic, and no steroids have been&#xD;
                  administered for at least 30 days&#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>John H Strickler</last_name>
    <role>Study Chair</role>
    <affiliation>Academic and Community Cancer Research United</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jorge Ramos, DO</last_name>
    <role>Study Director</role>
    <affiliation>Seagen Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35249</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Arizona</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pacific Shores Medical Group</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keck Medical Center / University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University School of Medicine</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Joseph Heritage Medical Group</name>
      <address>
        <city>Santa Rosa</city>
        <state>California</state>
        <zip>95403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Cancer Centers - Aurora</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lombardi Cancer Center / Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - South Region</name>
      <address>
        <city>Fort Myers</city>
        <state>Florida</state>
        <zip>33901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Florida Cancer Specialists - North Region</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute / Emory University School of Medicine</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637-1470</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Simon Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospitals and Clinics</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Institute / Wayne State University</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Cancer Centers of Nevada</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Case Western Reserve University / University Hospitals Cleveland Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwest Cancer Specialists, P.C.</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97227</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239-3098</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allegheny General Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Oncology-Nashville/Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Beaumont</name>
      <address>
        <city>Beaumont</city>
        <state>Texas</state>
        <zip>77702-1449</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Baylor Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Joe Arrington Cancer Research and Treatment Center</name>
      <address>
        <city>Lubbock</city>
        <state>Texas</state>
        <zip>79410</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - McAllen</name>
      <address>
        <city>McAllen</city>
        <state>Texas</state>
        <zip>78503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - San Antonio Medical Center</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology - Tyler</name>
      <address>
        <city>Tyler</city>
        <state>Texas</state>
        <zip>75702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Regional Medical Center Everett</name>
      <address>
        <city>Everett</city>
        <state>Washington</state>
        <zip>98201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance / University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109-1023</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aurora Research Institute Cancer Center</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint Luc</name>
      <address>
        <city>Brussels</city>
        <state>Other</state>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Antwerpen</name>
      <address>
        <city>Edegem</city>
        <state>Other</state>
        <zip>2650</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven campus Gasthuisberg</name>
      <address>
        <city>Leuven</city>
        <state>Other</state>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospitalier Jean Minjoz</name>
      <address>
        <city>Besancon</city>
        <state>Other</state>
        <zip>25030</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center Georges Francois Leclerc</name>
      <address>
        <city>Dijon</city>
        <state>Other</state>
        <zip>21000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Franco-Britannique - Fondation Cognacq-Jay</name>
      <address>
        <city>Levallois-Perret</city>
        <state>Other</state>
        <zip>92300</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Leon Berard - Centre regional de lutte contre le cancer Rhone-Alpes</name>
      <address>
        <city>Lyon</city>
        <state>Other</state>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital Saint-Antoine</name>
      <address>
        <city>Paris</city>
        <state>Other</state>
        <zip>75012</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Europeo di Oncologia</name>
      <address>
        <city>Milan</city>
        <state>Other</state>
        <zip>20141</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Niguarda Ca' Granda Hospital</name>
      <address>
        <city>Milan</city>
        <state>Other</state>
        <zip>20162</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Pisana - Ospedale S. Chiara</name>
      <address>
        <city>Pisa</city>
        <state>Other</state>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <state>Other</state>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <state>Other</state>
        <zip>08907</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Maranon</name>
      <address>
        <city>Madrid</city>
        <state>Other</state>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <state>Other</state>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>France</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 6, 2017</study_first_posted>
  <results_first_submitted>January 27, 2023</results_first_submitted>
  <results_first_submitted_qc>March 27, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">April 18, 2023</results_first_posted>
  <last_update_submitted>June 9, 2023</last_update_submitted>
  <last_update_submitted_qc>June 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER2</keyword>
  <keyword>ERBB2</keyword>
  <keyword>Colorectal cancer</keyword>
  <keyword>Seattle Genetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Trastuzumab</mesh_term>
    <mesh_term>Tucatinib</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 30, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03043313/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 11, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03043313/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 117 participants were enrolled at a total of 56 sites in the United States, Italy, France, Belgium, and Spain. The date of first participant enrollment was 23-Jun-2017. The date of last participant randomization was 22-Sep-2021.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Tucatinib+Trastuzumab (Cohort A)</title>
          <description>Non-randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
        </group>
        <group group_id="P2">
          <title>Tucatinib+Trastuzumab (Cohort B)</title>
          <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
        </group>
        <group group_id="P3">
          <title>Tucatinib Monotherapy (Cohort C)</title>
          <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="41"/>
                <participants group_id="P3" count="31"/>
              </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="45"/>
                <participants group_id="P2" count="41"/>
                <participants group_id="P3" count="31"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</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>Death</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>On Treatment</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>In follow up</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
      <group_list>
        <group group_id="B1">
          <title>Tucatinib+Trastuzumab (Cohort A)</title>
          <description>Non-randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
        </group>
        <group group_id="B2">
          <title>Tucatinib+Trastuzumab (Cohort B)</title>
          <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
        </group>
        <group group_id="B3">
          <title>Tucatinib Monotherapy (Cohort C)</title>
          <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
        </group>
        <group group_id="B4">
          <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="45"/>
            <count group_id="B2" value="39"/>
            <count group_id="B3" value="30"/>
            <count group_id="B4" value="114"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="52" lower_limit="24" upper_limit="71"/>
                    <measurement group_id="B2" value="57" lower_limit="31" upper_limit="77"/>
                    <measurement group_id="B3" value="59.5" lower_limit="29" upper_limit="75"/>
                    <measurement group_id="B4" value="56" lower_limit="24" upper_limit="77"/>
                  </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="19"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="15"/>
                    <measurement group_id="B4" value="66"/>
                  </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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="35"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="89"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="21"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="23"/>
                    <measurement group_id="B4" value="88"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="15"/>
                  </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>North America</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Europe</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="14"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status</title>
          <description>Measure Description: 0=Normal activity; 1=Symptoms but ambulatory; 2=In bed &lt;50% of the time; 3= In bed &gt;50% of the time; 4=100% bedridden; 5=Dead</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Grade 0</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="67"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 1</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Grade 2</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Confirmed Objective Response Rate (cORR) Per RECIST 1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B</title>
        <description>cORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).</description>
        <time_frame>Up to 46.6 months</time_frame>
        <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Confirmed Objective Response Rate (cORR) Per RECIST 1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B</title>
          <description>cORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).</description>
          <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.1" lower_limit="27.7" upper_limit="49.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>ORR by 12 Weeks of Treatment Per RECIST 1.1 According to BICR Assessment</title>
        <description>ORR per BICR by 12 Weeks is defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.</description>
        <time_frame>Up to 3 months</time_frame>
        <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tucatinib Monotherapy (Cohort C)</title>
            <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
          </group>
        </group_list>
        <measure>
          <title>ORR by 12 Weeks of Treatment Per RECIST 1.1 According to BICR Assessment</title>
          <description>ORR per BICR by 12 Weeks is defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.</description>
          <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.6" lower_limit="19.2" upper_limit="39.5"/>
                    <measurement group_id="O2" value="3.3" lower_limit="0.1" upper_limit="17.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR) Per RECIST 1.1 According to BICR Assessment</title>
        <description>DOR is defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first.</description>
        <time_frame>Up to 44.7 months</time_frame>
        <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tucatinib Monotherapy (Cohort C)</title>
            <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR) Per RECIST 1.1 According to BICR Assessment</title>
          <description>DOR is defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first.</description>
          <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.4" lower_limit="8.5" upper_limit="20.5"/>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">Not enough events in Cohort C to calculate Median or Lower and Upper Limits.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-Free Survival (PFS) Per RECIST 1.1 According to BICR Assessment for Pooled Cohorts A+B</title>
        <description>PFS is defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST 1.1) or death from any cause, whichever occurs first.</description>
        <time_frame>Up to 46.6 months</time_frame>
        <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-Free Survival (PFS) Per RECIST 1.1 According to BICR Assessment for Pooled Cohorts A+B</title>
          <description>PFS is defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST 1.1) or death from any cause, whichever occurs first.</description>
          <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.2" lower_limit="4.2" upper_limit="10.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival (OS) in Pooled Cohorts A+B</title>
        <description>OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.</description>
        <time_frame>Up to 53 months</time_frame>
        <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS) in Pooled Cohorts A+B</title>
          <description>OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.</description>
          <population>The Full Analysis Set includes all subjects who were enrolled and received any amount of study treatment and had HER2+ tumors as defined by one or more protocol required local tests.</population>
          <units>Months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.1" lower_limit="20.3" upper_limit="36.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (AEs)</title>
        <description>An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab).</description>
        <time_frame>Up to 49.3 months</time_frame>
        <population>The safety analysis set includes subjects who received any amount of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tucatinib Monotherapy (Cohort C)</title>
            <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (AEs)</title>
          <description>An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab).</description>
          <population>The safety analysis set includes subjects who received any amount of study treatment.</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="86"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tucatinib-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63"/>
                    <measurement group_id="O2" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trastuzumab-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any grade 3-5 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tucatinib-related grade 3-5 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trastuzumab-related grade 3-5 TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any Treatment-Emergent Serious AE (TESAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tucatinib-related TESAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trastuzumab-related TESAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to death</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>Discontinuation of any study treatment due to TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuation of tucatinib due to TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuation of tucatinib due to tucatinib-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuation of trastuzumab due to TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discontinuation of trastuzumab due to trastuzumab-related TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With AEs Resulting in Dose Modification</title>
        <description>Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.</description>
        <time_frame>Up to 49.3 months</time_frame>
        <population>The safety analysis set includes subjects who received any amount of study treatment.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tucatinib Monotherapy (Cohort C)</title>
            <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With AEs Resulting in Dose Modification</title>
          <description>Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.</description>
          <population>The safety analysis set includes subjects who received any amount of study treatment.</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="86"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Tucatinib dose held</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tucatinib dose reduced</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trastuzumab dose held</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trastuzumab infusion interrupted (received full dose within 24 hrs)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trastuzumab infusion stopped early (full dose not received)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="NA">Tucatinib monotherapy arm</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)</title>
        <description>Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.</description>
        <time_frame>Up to 49.3 months</time_frame>
        <population>Participants in the safety analysis set with both baseline and post-baseline results for each test.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tucatinib Monotherapy (Cohort C)</title>
            <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)</title>
          <description>Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.</description>
          <population>Participants in the safety analysis set with both baseline and post-baseline results for each test.</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="85"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hemoglobin decreased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin decreased, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin decreased, Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin decreased, Grade 4</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>Leukocytes decreased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes decreased, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes decreased, Grade 3</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>Leukocytes decreased, Grade 4</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>Neutrophils decreased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils decreased, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils decreased, Grade 3</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>Neutrophils decreased, Grade 4</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>Platelets decreased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets decreased, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets decreased, Grade 3</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>Platelets decreased, Grade 4</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_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry)</title>
        <description>Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.</description>
        <time_frame>Up to 49.3 months</time_frame>
        <population>Participants in the safety analysis set with both baseline and post-baseline results for each test.</population>
        <group_list>
          <group group_id="O1">
            <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
            <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
          </group>
          <group group_id="O2">
            <title>Tucatinib Monotherapy (Cohort C)</title>
            <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry)</title>
          <description>Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.</description>
          <population>Participants in the safety analysis set with both baseline and post-baseline results for each test.</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="85"/>
                <count group_id="O2" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Potassium increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium increased, Grade 2</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>Potassium increased, Grade 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>
              <title>Potassium increased, Grade 4</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>Potassium decreased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium decreased, Grade 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>Potassium decreased, Grade 3</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>Potassium decreased, Grade 4</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>Aspartate Aminotransferase increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Aminotransferase increased, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Aminotransferase increased, Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Aspartate Aminotransferase increased, Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Aminotransferase increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Aminotransferase increased, Grade 2</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>Alanine Aminotransferase increased, Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Aminotransferase increased, Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine increased, Grade 3</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>Creatinine increased, Grade 4</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>Alkaline Phosphatase increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline Phosphatase increased, Grade 2</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>Alkaline Phosphatase increased, Grade 3</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>Alkaline Phosphatase increased, Grade 4</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>Total Bilirubin increased, Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Bilirubin increased, Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Bilirubin increased, Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Bilirubin increased, Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Non-serious adverse events were followed during the safety reporting period (from study Day 1 (pre-dose) through 30 days after the last study treatment), which lasted for up to 49.3 months. All-cause mortality and serious adverse events (SAEs) were monitored for up to 53 months.</time_frame>
      <desc>Adverse events (AEs) for Cohorts A and B were analyzed together. All-cause mortality, SAE, and non-serious AE data are presented separately for Cohort C Pre-crossover and Post-crossover.&#xD;
All-Cause Mortality is reported for all enrolled patients, regardless of whether or not they received study drug. SAEs and non-serious AEs are reported only for those patients who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tucatinib+Trastuzumab (Cohorts A+B)</title>
          <description>Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle. Trastuzumab 8 mg/kg by IV infusion on Day 1 of Cycle 1 and 6 mg/kg on Day 1 of each subsequent cycle.</description>
        </group>
        <group group_id="E2">
          <title>Cohort C (Pre-Crossover)</title>
          <description>Randomized cohort. Tucatinib 300 mg PO BID on Days 1 to 21 of each 21-day cycle.</description>
        </group>
        <group group_id="E3">
          <title>Cohort C (Post-Crossover)</title>
          <description>Of the 30 participants who received tucatinib monotherapy, 28 crossed over to receive tucatinib + trastuzumab therapy.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v24.0</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="39" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="31"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Colitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Duodenal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastrointestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Large intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rectal perforation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pyelonephritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </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="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Renal colic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</frequency_threshold>
        <default_vocab>MedDRA v24.0</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="82" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blepharospasm</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Eye pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="55" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Haematochezia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="29" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Gastrointestinal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Eructation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Proctalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Proctitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Salivary hypersecretion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Glossodynia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Oral pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Tooth loss</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="37" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Influenza like illness</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Peripheral swelling</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Xerosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hepatic pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>COVID-19 pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nail infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Kidney infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Furuncle</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hordeolum</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rash pustular</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Procedural pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Blood alkaline phosphatase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Weight increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </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="16" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypoalbuminaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hypercreatinaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Peripheral sensory neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Hemiparesis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Neurotoxicity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </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="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pollakiuria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Pelvic pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Breast pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vaginal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Vulvovaginal dryness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Wheezing</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dysphonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Sinus pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Throat irritation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis acneiform</sub_title>
                <counts group_id="E1" subjects_affected="16" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dry skin</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Onychomadesis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nail disorder</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Urticaria</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Pain of skin</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Onychoclasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Onycholysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Rash pruritic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Social circumstances</title>
            <event_list>
              <event>
                <sub_title>Pregnancy of partner</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Lymphoedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="86"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="28"/>
              </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>There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Chief Medical Officer</name_or_title>
      <organization>Seagen Inc.</organization>
      <phone>(855)473-2436</phone>
      <email>medinfo@seagen.com</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/NCT03043313
org study id: SGNTUC-017
secondary id: NCI-2017-01107
secondary id: ACCRU-GI-1617
secondary id: P30CA015083
nct id: NCT03043313
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This trial studies how well the drug tucatinib works when given with trastuzumab and when
      given by itself. The participants in this trial have HER2-positive (HER2+) metastatic
      colorectal cancer (mCRC). 'Metastatic' means that the cancer has spread to other parts of the
      body.

      In the first part of this study, participants enrolled into Cohort A and received both
      tucatinib and trastuzumab. In the second part of this study, participants are randomly
      assigned to either Cohort B or Cohort C. Participants in Cohort B will receive tucatinib and
      trastuzumab. Participants in Cohort C will receive tucatinib. Participants in Cohort C who do
      not respond to therapy may have an option to receive tucatinib plus trastuzumab.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Confirmed Objective Response Rate (cORR) Per RECIST 1.1 Per Blinded Independent Central Review (BICR) in Pooled Cohorts A+B
time frame: Up to 46.6 months
description: cORR is defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
measure: ORR by 12 Weeks of Treatment Per RECIST 1.1 According to BICR Assessment
time frame: Up to 3 months
description: ORR per BICR by 12 Weeks is defined as the percentage of participants with CR or PR by 12 weeks of treatment, and before time of crossover (Cohort C), whichever comes earlier.
measure: Duration of Response (DOR) Per RECIST 1.1 According to BICR Assessment
time frame: Up to 44.7 months
description: DOR is defined as the time from the first objective response (CR or PR that is subsequently confirmed) to documented PD per RECIST 1.1 or death from any cause, whichever occurs first.
measure: Progression-Free Survival (PFS) Per RECIST 1.1 According to BICR Assessment for Pooled Cohorts A+B
time frame: Up to 46.6 months
description: PFS is defined as the time from start of study treatment (Cohort A) or date of randomization (Cohort B) to documented disease progression (as determined by BICR per RECIST 1.1) or death from any cause, whichever occurs first.
measure: Overall Survival (OS) in Pooled Cohorts A+B
time frame: Up to 53 months
description: OS is defined as the time from start of study treatment (Cohort A) or randomization (Cohort B) to date of death due to any cause.
measure: Number of Participants With Adverse Events (AEs)
time frame: Up to 49.3 months
description: An AE is any untoward medical occurrence in a patient or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Treatment emergent AEs (TEAEs) are defined as events that are new or worsened on or after receiving the first dose of study treatment (tucatinib or trastuzumab) and up through 30 days after the last dose of study treatment (tucatinib or trastuzumab).
measure: Number of Participants With AEs Resulting in Dose Modification
time frame: Up to 49.3 months
description: Dose modification included dose reduction and dose withheld by investigator due to AEs. Dose holds were defined as any instances where planned administration of the study drug was temporarily withheld or interrupted at the direction of the treating physician. Dose reductions of trastuzumab were not allowed; if trastuzumab could not be restarted after being held for a TEAE, it was discontinued.
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)
time frame: Up to 49.3 months
description: Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.
measure: Number of Participants With Treatment-Emergent Laboratory Abnormalities (Chemistry)
time frame: Up to 49.3 months
description: Treatment emergent laboratory abnormalities are defined as abnormalities that are new or worsened on or after receiving the first dose of study treatment and up through 30 days after the last dose of study treatment. NCI CTCAE v5.0 is used for creatinine increased. NCI CTCAE v4.03 is used for the other lab parameters.
arm group label: Cohort A: Tucatinib + Trastuzumab
arm group type: Experimental
description: Non-randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
arm group label: Cohort B: Tucatinib + Trastuzumab
arm group type: Experimental
description: Randomized cohort. Participants take tucatinib twice per day orally on Days 1-21 and trastuzumab intravenously (into the vein; IV) on Day 1. Cycles repeat every 21 days.
arm group label: Cohort C: Tucatinib Monotherapy
arm group type: Experimental
description: Randomized cohort. Participants take tucatinib twice per orally every day. Participants who do not respond to therapy may have the option to receive tucatinib and trastuzumab.
intervention type: Drug
intervention name: Trastuzumab
description: Given intravenously (into the vein; IV)
arm group label: Cohort A: Tucatinib + Trastuzumab
arm group label: Cohort B: Tucatinib + Trastuzumab
other name: Herceptin
intervention type: Drug
intervention name: Tucatinib
description: Given orally
arm group label: Cohort A: Tucatinib + Trastuzumab
arm group label: Cohort B: Tucatinib + Trastuzumab
arm group label: Cohort C: Tucatinib Monotherapy
other name: ARRY-380
other name: ONT-380
other name: TUKYSA
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: John H Strickler
role: Study Chair
affiliation: Academic and Community Cancer Research United
last name: Jorge Ramos, DO
role: Study Director
affiliation: Seagen Inc.
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country: Belgium
country: France
country: Italy
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
mesh term: Trastuzumab
mesh term: Tucatinib
provided document: 
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participant flow: 
baseline: 
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reported events: 
certain agreements: 
point of contact: 