<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/NCT04468607</url>
  </required_header>
  <id_info>
    <org_study_id>GO41751</org_study_id>
    <nct_id>NCT04468607</nct_id>
  </id_info>
  <brief_title>A Study of BLYG8824A in Participants With Locally Advanced or Metastatic Colorectal Cancer</brief_title>
  <official_title>A Phase I, Open-Label, Dose-Escalation Study Of The Safety And Pharmacokinetics Of BLYG8824A Administered Intravenously In Patients With Locally Advanced Or Metastatic Colorectal Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genentech, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will&#xD;
      make a preliminary assessment of the anti-tumor activity of BLYG8824A in patients with&#xD;
      locally advanced or metastatic colorectal cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 31, 2020</start_date>
  <completion_date type="Anticipated">January 2, 2026</completion_date>
  <primary_completion_date type="Anticipated">January 2, 2026</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Open Label</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and Nature of DLTs</measure>
    <time_frame>Approximately 48 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Patricipants with Adverse Events</measure>
    <time_frame>Approximately 48 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number Of Cycles Received</measure>
    <time_frame>Approximately 48 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Intensity</measure>
    <time_frame>Approximately 48 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose(s) MTD(s) of BLYG8824A</measure>
    <time_frame>Approximately 48 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of BLYG8824A</measure>
    <time_frame>At predifined interevals from Cycle 1 Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>Approximately 48 months</time_frame>
    <description>ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Approximately 48 months</time_frame>
    <description>Duration of response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of Anti-drug Antibodies (ADAs)</measure>
    <time_frame>Cycle 1, Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Colorectal Cancer</condition>
  <arm_group>
    <arm_group_label>Dose-Escalation Stage</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be assigned sequentially to escalating doses of BLYG8824A, up to the maximum tolerated dose (MTD).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Expansion Stage</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Once dose escalation is completed and the MTD (or MAD) has been identified, a recommended expansion dose will be proposed for the dose-expansion stage of the trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BLYG8824A</intervention_name>
    <description>BLYG8824A will be administered at a flat dose independent of body weight.</description>
    <arm_group_label>Dose-Escalation Stage</arm_group_label>
    <arm_group_label>Dose-Expansion Stage</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ECOG performance status of 0 or 1&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
          -  Histologically or cytologically documented invasive CRC: incurable, unresectable,&#xD;
             locally advanced or metastatic CRC previously treated with multimodality therapy or&#xD;
             mCRC&#xD;
&#xD;
          -  Locally advanced or metastatic CRC that has relapsed or is refractory to established&#xD;
             therapies&#xD;
&#xD;
          -  Prior disease progression (or intolerance) following oxaliplatin, irinotecan,&#xD;
             fluoropyrimidines, and anti-EGFR monoclonal antibodies&#xD;
&#xD;
          -  An archival tissue specimen or fresh baseline biopsy (when archival is not available)&#xD;
             is required for enrollment into the study&#xD;
&#xD;
          -  Measurable disease, according to the Response Evaluation Criteria in Solid Tumors&#xD;
             (RECIST) v1.1. Non-measurable evaluable disease is acceptable for dose-escalation.&#xD;
&#xD;
          -  Adequate hematologic and end organ function&#xD;
&#xD;
          -  Acute, clinically significant treatment-related toxicity from prior therapy resolved&#xD;
             to Grade ≤ 1 prior to study entry&#xD;
&#xD;
        Expansion Cohort-Specific Inclusion Criteria&#xD;
&#xD;
          -  MSS or MSI-L disease as determined by polymerase chain reaction (PCR) and/or IHC&#xD;
&#xD;
          -  Measurable disease by RECIST v1.1 with at least one measurable target lesion in the&#xD;
             expansion cohort&#xD;
&#xD;
          -  Progression must have occurred during or after most recent treatment for locally&#xD;
             advanced or metastatic colorectal cancer&#xD;
&#xD;
          -  For patients enrolled in either a dedicated biopsy cohort or other expansion cohorts&#xD;
             where biopsy is clinically feasible, willingness to consent to mandatory fresh&#xD;
             pretreatment and on-treatment biopsies of safely accessible tumor lesions&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or breastfeeding, or intending to become pregnant during the study or within&#xD;
             4 months after the final dose of BLYG8824A&#xD;
&#xD;
          -  Significant cardiopulmonary dysfunction&#xD;
&#xD;
          -  Known clinically significant liver disease&#xD;
&#xD;
          -  Positive serologic or PCR test results for acute or chronic HBV infection&#xD;
&#xD;
          -  Acute or chronic HCV infection&#xD;
&#xD;
          -  HIV seropositivity&#xD;
&#xD;
          -  Poorly controlled Type 2 diabetes mellitus&#xD;
&#xD;
          -  Current treatment with medications that are well known to prolong the QT interval&#xD;
&#xD;
          -  Primary CNS malignancy, untreated CNS metastases, or active CNS metastases&#xD;
&#xD;
          -  Leptomeningeal disease&#xD;
&#xD;
          -  Spinal cord compression that has not been definitively treated with surgery and/or&#xD;
             radiation&#xD;
&#xD;
          -  History of autoimmune disease&#xD;
&#xD;
          -  Prior allogeneic stem cell or solid organ transplantation&#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>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Genentech, Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Reference Study ID Number: GO41751 https://forpatients.roche.com/</last_name>
    <phone>888-662-6728 (U.S. and Canada)</phone>
    <email>global-roche-genentech-trials@gene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre; Medical Oncology</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Centre; Clinical Trials Pharmacy</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 2M9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Clinica Universitaria de Navarra</name>
      <address>
        <city>Pamplona</city>
        <state>Navarra</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Vall d'Hebron - PPDS</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>START Madrid-FJD, Hospital Fundacion Jimenez Diaz</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Canada</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>July 8, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>September 1, 2023</last_update_submitted>
  <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Colorectal Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04468607
org study id: GO41751
nct id: NCT04468607
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the safety, tolerability, and pharmacokinetics of BLYG8824A and will
      make a preliminary assessment of the anti-tumor activity of BLYG8824A in patients with
      locally advanced or metastatic colorectal cancer.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: Open Label
measure: Incidence and Nature of DLTs
time frame: Approximately 48 months
measure: Number of Patricipants with Adverse Events
time frame: Approximately 48 months
measure: Number Of Cycles Received
time frame: Approximately 48 months
measure: Dose Intensity
time frame: Approximately 48 months
measure: Maximum Tolerated Dose(s) MTD(s) of BLYG8824A
time frame: Approximately 48 months
measure: Serum Concentration of BLYG8824A
time frame: At predifined interevals from Cycle 1 Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)
measure: Overall Response Rate (ORR)
time frame: Approximately 48 months
description: ORR is defined as the proportion of patients with a complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
measure: Duration of Response (DOR)
time frame: Approximately 48 months
description: Duration of response (DOR), defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1
measure: Presence of Anti-drug Antibodies (ADAs)
time frame: Cycle 1, Day 1; Cycle 2 Day 1; Cycles ≥ 3, Day 1; Treatment Completion/ Discontinuation (Cycle length: 21 days)
arm group label: Dose-Escalation Stage
arm group type: Experimental
description: Participants will be assigned sequentially to escalating doses of BLYG8824A, up to the maximum tolerated dose (MTD).
arm group label: Dose-Expansion Stage
arm group type: Experimental
description: Once dose escalation is completed and the MTD (or MAD) has been identified, a recommended expansion dose will be proposed for the dose-expansion stage of the trial.
intervention type: Drug
intervention name: BLYG8824A
description: BLYG8824A will be administered at a flat dose independent of body weight.
arm group label: Dose-Escalation Stage
arm group label: Dose-Expansion Stage
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Genentech, Inc.
last name: Reference Study ID Number: GO41751 https://forpatients.roche.com/
phone: 888-662-6728 (U.S. and Canada)
email: global-roche-genentech-trials@gene.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
country: Australia
country: Canada
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Colorectal Neoplasms
sharing ipd: Yes
ipd description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).