xml: <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/NCT06004245</url>
    </required_header>
    <id_info>
      <org_study_id>BP44474</org_study_id>
      <secondary_id>2023-503170-20-00</secondary_id>
      <nct_id>NCT06004245</nct_id>
    </id_info>
    <brief_title>A Study to Evaluate the Safety, Pharmacokinetics, and Anti-Tumor Activity of RO7589831 in Participants With Advanced Solid Tumors</brief_title>
    <official_title>A Phase I, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Anti-Tumor Activity of RO7589831 in Participants With Advanced Solid Tumors Harboring Microsatellite Instability (MSI) and/or Deficient Mismatch Repair (dMMR)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hoffmann-La Roche</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Hoffmann-La Roche</source>
    <oversight_info>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose&#xD;
        expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and&#xD;
        preliminary anti-tumor activity of RO7589831 monotherapy in participants with MSI and/or dMMR&#xD;
        advanced solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 15, 2023</start_date>
    <completion_date type="Anticipated">December 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 22, 2025</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>
      <intervention_model_description>This is an open label study. Participants will be assigned to dose cohorts in the order in which they are enrolled. However, if two or more cohorts in the same part of the study are open for enrollment at the same time, participants will be randomized into these cohorts.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Incidence of Adverse Events, with Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)</measure>
      <time_frame>From first dose of study drug until 30 days after last dose of study drug (up to approximately 15 months)</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of Dose-Limiting Toxicities</measure>
      <time_frame>Cycle 1 (1 cycle is 3 weeks)</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Maximum Plasma Concentration Observed (Cmax) of RO7589831</measure>
      <time_frame>At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time of Maximum Plasma Concentration Observed (Tmax) of RO7589831</measure>
      <time_frame>At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area Under the Plasma Concentration-Time Curve (AUC) of RO7589831</measure>
      <time_frame>At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apparent Oral Clearance (CL/F) of RO7589831</measure>
      <time_frame>At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Volume of Distribution (V/F) of RO7589831</measure>
      <time_frame>At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Terminal Half-Life (T1/2) of RO7589831</measure>
      <time_frame>At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective Response Rate</measure>
      <time_frame>From start of study treatment until end of follow-up (up to approximately 36 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate</measure>
      <time_frame>From start of study treatment until end of follow-up (up to approximately 36 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response</measure>
      <time_frame>From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-Free Survival, as Assessed by the Investigator</measure>
      <time_frame>From start of study treatment to the first occurrence of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>From start of study treatment to the time of death from any cause (up to approximately 36 months)</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">220</enrollment>
    <condition>Advanced Solid Tumors</condition>
    <arm_group>
      <arm_group_label>Part I: RO7589831 Dose Escalation</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Part II: RO7589831 Dose Expansion</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>RO7589831</intervention_name>
      <description>RO7589831 will be administered orally and once daily (QD) in 3-week cycles.</description>
      <arm_group_label>Part I: RO7589831 Dose Escalation</arm_group_label>
      <arm_group_label>Part II: RO7589831 Dose Expansion</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1&#xD;
  &#xD;
            -  Have a locally confirmed microsatellite instability (MSI) and/or deficient mismatch&#xD;
               repair (dMMR), histologically or cytologically documented advanced (unresectable&#xD;
               and/or metastatic) solid tumor&#xD;
  &#xD;
            -  Have received and then progressed following or are intolerant to at least 1 standard&#xD;
               treatment regimen in the advanced setting&#xD;
  &#xD;
            -  Presence of measurable disease according to Response Evaluation Criteria in Solid&#xD;
               Tumors (RECIST) version 1.1&#xD;
  &#xD;
            -  Life expectancy of at least (≥)12 weeks&#xD;
  &#xD;
            -  Availability of formaldehyde-fixed paraffin-embedded (FFPE) archival tumor tissue for&#xD;
               submission to Sponsor/central laboratory for retrospective central testing; for&#xD;
               participants without archival tissue, a biopsy from either primary or metastatic tumor&#xD;
               lesion, deemed medically feasible, must be taken&#xD;
  &#xD;
            -  Adequate hematologic, end-organ, and cardiovascular function, as defined in the&#xD;
               protocol&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inability or unwillingness to swallow pills&#xD;
  &#xD;
            -  Malabsorption syndrome or other condition that would interfere with enteral absorption&#xD;
  &#xD;
            -  Known hypersensitivity or intolerance to ingredients from the study drug formulation&#xD;
               including patients with rare genetic disorders such as galactosaemia,&#xD;
               glucose-galactose intolerance or congenital lactase deficiency&#xD;
  &#xD;
            -  Known uncontrolled central nervous system (CNS) metastases (progressing or requiring&#xD;
               anticonvulsants or corticosteroids for symptomatic control) and/or carcinomatous&#xD;
               meningitis&#xD;
  &#xD;
            -  Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but&#xD;
               not limited to tuberculosis and atypical mycobacterial disease), parasitic, or other&#xD;
               infection (excluding fungal infections of nail beds), or any major episode of&#xD;
               infection requiring treatment with intravenous antibiotics or hospitalization within 2&#xD;
               weeks prior to the start of drug administration (related to the completion of the&#xD;
               course of antibiotics, except if for tumor fever) or 6 months for any intracranial&#xD;
               abscess&#xD;
  &#xD;
            -  Has a positive test at screening for hepatitis B virus, hepatitis C virus, or for&#xD;
               human immodeficiency virus (HIV), per local diagnostic standard and in accordance with&#xD;
               local laws and regulations&#xD;
  &#xD;
            -  Uncontrolled diabetes or symptomatic hyperglycemia (i.e., well controlled defined as a&#xD;
               screening hemoglobin A1c &lt;8% and no urinary ketoacidosis)&#xD;
  &#xD;
            -  Alcohol or drug dependence or abuse&#xD;
  &#xD;
            -  Patients with known Werner (WRN) syndrome&#xD;
  &#xD;
            -  Prior treatment with any WRN helicase inhibitor&#xD;
  &#xD;
            -  Pregnancy, breastfeeding, or intention of becoming pregnant during the study&#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>Hoffmann-La Roche</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Reference Study ID Number: BP44474 https://forpatients.roche.com/</last_name>
      <phone>888-662-6728 (U.S. Only)</phone>
      <email>global-roche-genentech-trials@gene.com</email>
    </overall_contact>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 16, 2023</study_first_submitted>
    <study_first_submitted_qc>August 16, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 22, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Deficient mismatch repair</keyword>
    <keyword>dMMR</keyword>
    <keyword>Microsatellite instability</keyword>
    <keyword>MSI</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Microsatellite Instability</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).&#xD;
  Roche's Global Policy on the Sharing of Clinical Information describes studies which are eligible for data sharing and how to request access (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).</ipd_description>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06004245
  org study id: BP44474
  secondary id: 2023-503170-20-00
  nct id: NCT06004245
  lead sponsor: 
  is fda regulated drug: Yes
  is fda regulated device: No
  This is a first-in-human, Phase I, open-label, multicenter, dose-escalation and dose
        expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and
        preliminary anti-tumor activity of RO7589831 monotherapy in participants with MSI and/or dMMR
        advanced solid tumors.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: This is an open label study. Participants will be assigned to dose cohorts in the order in which they are enrolled. However, if two or more cohorts in the same part of the study are open for enrollment at the same time, participants will be randomized into these cohorts.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of Adverse Events, with Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)
  time frame: From first dose of study drug until 30 days after last dose of study drug (up to approximately 15 months)
  measure: Incidence of Dose-Limiting Toxicities
  time frame: Cycle 1 (1 cycle is 3 weeks)
  measure: Maximum Plasma Concentration Observed (Cmax) of RO7589831
  time frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
  measure: Time of Maximum Plasma Concentration Observed (Tmax) of RO7589831
  time frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
  measure: Area Under the Plasma Concentration-Time Curve (AUC) of RO7589831
  time frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
  measure: Apparent Oral Clearance (CL/F) of RO7589831
  time frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
  measure: Volume of Distribution (V/F) of RO7589831
  time frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
  measure: Terminal Half-Life (T1/2) of RO7589831
  time frame: At prespecified timepoints in Cycles 1, 2, and 3, and every 2 cycles thereafter (1 cycle is 3 weeks) until last dose of study drug (up to approximately 15 months)
  measure: Objective Response Rate
  time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
  measure: Disease Control Rate
  time frame: From start of study treatment until end of follow-up (up to approximately 36 months)
  measure: Duration of Response
  time frame: From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
  measure: Progression-Free Survival, as Assessed by the Investigator
  time frame: From start of study treatment to the first occurrence of documented disease progression or death from any cause, whichever occurs first (up to approximately 36 months)
  measure: Overall Survival
  time frame: From start of study treatment to the time of death from any cause (up to approximately 36 months)
  arm group label: Part I: RO7589831 Dose Escalation
  arm group type: Experimental
  arm group label: Part II: RO7589831 Dose Expansion
  arm group type: Experimental
  intervention type: Drug
  intervention name: RO7589831
  description: RO7589831 will be administered orally and once daily (QD) in 3-week cycles.
  arm group label: Part I: RO7589831 Dose Escalation
  arm group label: Part II: RO7589831 Dose Expansion
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Clinical Trials
  role: Study Director
  affiliation: Hoffmann-La Roche
  last name: Reference Study ID Number: BP44474 https://forpatients.roche.com/
  phone: 888-662-6728 (U.S. Only)
  email: global-roche-genentech-trials@gene.com
  responsible party type: Sponsor
  mesh term: Microsatellite Instability
  sharing ipd: No
  ipd description: For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/).
  Roche's Global Policy on the Sharing of Clinical Information describes studies which are eligible for data sharing and how to request access (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).