<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/NCT04434469</url>
  </required_header>
  <id_info>
    <org_study_id>GO41582</org_study_id>
    <nct_id>NCT04434469</nct_id>
  </id_info>
  <brief_title>A Study Evaluating The Safety And Pharmacokinetics Of Escalating Doses Of RO7297089 In Patients With Relapsed Or Refractory Multiple Myeloma</brief_title>
  <official_title>An Open-Label, Multicenter, Phase I Trial Evaluating The Safety And Pharmacokinetics Of Escalating Doses Of RO7297089 In Patients With Relapsed Or Refractory Multiple Myeloma</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a first-in-human Phase I, open-label, multicenter, global, dose-escalation study&#xD;
      designed to evaluate the safety, tolerability, and pharmacokinetics of RO7297089 and make a&#xD;
      preliminary assessment of anti-tumor activity in patients with R/R MM for whom no established&#xD;
      therapy for MM is appropriate and available or who are intolerant to those established&#xD;
      therapies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 8, 2020</start_date>
  <completion_date type="Actual">February 16, 2022</completion_date>
  <primary_completion_date type="Actual">February 16, 2022</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of participants with Adverse Events (AEs), including Dose Limiting Toxicities (DLTs)</measure>
    <time_frame>Baseline up to approximately 3 years</time_frame>
    <description>Adverse event severity will be graded according to NCI CTCAE v5.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the Curve (AUC) of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Concentration Observed (Cmax) of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Concentration Observed (tmax) of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Concentration Observed (Cmin) of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution at Steady State of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Half-life of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total clearance of RO7297089</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Baseline up to approximately 3 years</time_frame>
    <description>ORR is defined as a Stringent Complete Response (Scr), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) as determined by the Investigator according to International Myeloma Working Group (IMWG) Uniform Response Criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration Of Response (DOR)</measure>
    <time_frame>Baseline up to approximately 3 years</time_frame>
    <description>DOR is 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 IMWG Uniform Response Criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevalence Of Anti-Drug Antibodies (ADAs)</measure>
    <time_frame>Baseline up to approximately 3 years (detailed time frame provided in description)</time_frame>
    <description>Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Refractory Multiple Myeloma</condition>
  <condition>Relapsed Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm A Flat Dose Escalation: RO7297089</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in Arm A will receive the target dose of RO7297089 as a flat dose at each scheduled study drug administration visit</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B Split Dose Escalation: RO7297089</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in Arm B will receive the first target dose of RO7297089 as a split dose divided over two days (Days 1 and 2). The full target dose will be administered at subsequent study drug administration visits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C Step Dose Escalation: RO7297089</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in Arm C will receive the first cycle of RO7297089 as a single-step dose escalation. The Cycle 1 Day 1 dose will be lower than the target dose. The full target dose will be administered at subsequent study drug administration visits.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Phase I Expansion Stage: RO7297089</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>After dose escalation has been completed, approximately 30 patients will be enrolled in the expansion stage. Participants will receive RO7297089 at the recommended phase 2 dose (at or below the maximum tolerated dose).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RO7297089</intervention_name>
    <description>RO7297089 will be given via intravenous (IV) infusion</description>
    <arm_group_label>Arm A Flat Dose Escalation: RO7297089</arm_group_label>
    <arm_group_label>Arm B Split Dose Escalation: RO7297089</arm_group_label>
    <arm_group_label>Arm C Step Dose Escalation: RO7297089</arm_group_label>
    <arm_group_label>Phase I Expansion Stage: RO7297089</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks&#xD;
&#xD;
          -  R/R MM for which no established therapy for MM is appropriate and available or be&#xD;
             intolerant to those established therapies&#xD;
&#xD;
          -  Measurable disease&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate&#xD;
             for the treatment of cancer within 4 weeks before first RO7297089 infusion&#xD;
&#xD;
          -  Prior treatment with systemic immunotherapeutic agents within 12 weeks or 5 half-lives&#xD;
             of the drug, whichever is shorter, before first RO7297089 infusion&#xD;
&#xD;
          -  Prior treatment with CAR-T therapy within 90 days before first study drug&#xD;
             administration&#xD;
&#xD;
          -  Treatment with any chemotherapeutic agent, or treatment with any other anti-cancer&#xD;
             agent (investigational or otherwise) within 4 weeks or 5 half-lives of the drug,&#xD;
             whichever is shorter, prior to first RO7297089 infusion&#xD;
&#xD;
          -  Autologous stem cell transplantation within 100 days prior to first RO7297089 infusion&#xD;
&#xD;
          -  Allogeneic stem cell transplantation within 180 days prior to first RO7297089 infusion&#xD;
             or requiring immunosuppression for treatment or prophylaxis of graft versus host&#xD;
             disease&#xD;
&#xD;
          -  Primary or secondary plasma cell leukemia&#xD;
&#xD;
          -  Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection&#xD;
             requiring treatment with IV anti-microbial therapy within 14 days prior to first&#xD;
             RO7297089 infusion&#xD;
&#xD;
          -  Significant cardiovascular disease&#xD;
&#xD;
          -  Current CNS involvement by MM&#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>
  <location>
    <facility>
      <name>Concord Repatriation General Hospital</name>
      <address>
        <city>Concord</city>
        <state>New South Wales</state>
        <zip>2139</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LIVERPOOL HOSPITAL; HAEMATOLOGY; Ingham Institute for Medical Research</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <zip>2170</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital; Haematology Clinical Trials</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Vincent's Hospital Melbourne</name>
      <address>
        <city>Fitzroy</city>
        <state>South Australia</state>
        <zip>3065</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peter Mac Callum Cancer Center</name>
      <address>
        <city>East Melbourne</city>
        <state>Victoria</state>
        <zip>3002</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Gent</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rigshospitalet</name>
      <address>
        <city>København Ø</city>
        <zip>2100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vejle Sygehus; Onkologisk Afdeling</name>
      <address>
        <city>Vejle</city>
        <zip>7100</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo Universitetssykehus HF; Ullevål sykehus</name>
      <address>
        <city>Oslo</city>
        <zip>0450</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Denmark</country>
    <country>Norway</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 12, 2020</study_first_submitted>
  <study_first_submitted_qc>June 12, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 16, 2020</study_first_posted>
  <last_update_submitted>June 1, 2022</last_update_submitted>
  <last_update_submitted_qc>June 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2022</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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</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>
  <pending_results>
    <submitted>February 23, 2023</submitted>
  </pending_results>
  <!-- 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/NCT04434469
org study id: GO41582
nct id: NCT04434469
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a first-in-human Phase I, open-label, multicenter, global, dose-escalation study
      designed to evaluate the safety, tolerability, and pharmacokinetics of RO7297089 and make a
      preliminary assessment of anti-tumor activity in patients with R/R MM for whom no established
      therapy for MM is appropriate and available or who are intolerant to those established
      therapies.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of participants with Adverse Events (AEs), including Dose Limiting Toxicities (DLTs)
time frame: Baseline up to approximately 3 years
description: Adverse event severity will be graded according to NCI CTCAE v5.0
measure: Serum Concentration of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Area under the Curve (AUC) of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Maximum Concentration Observed (Cmax) of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Time to Maximum Concentration Observed (tmax) of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Minimum Concentration Observed (Cmin) of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Volume of Distribution at Steady State of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Half-life of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Total clearance of RO7297089
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
measure: Objective Response Rate (ORR)
time frame: Baseline up to approximately 3 years
description: ORR is defined as a Stringent Complete Response (Scr), Complete Response (CR), Very Good Partial Response (VGPR) or Partial Response (PR) as determined by the Investigator according to International Myeloma Working Group (IMWG) Uniform Response Criteria
measure: Duration Of Response (DOR)
time frame: Baseline up to approximately 3 years
description: DOR is 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 IMWG Uniform Response Criteria
measure: Prevalence Of Anti-Drug Antibodies (ADAs)
time frame: Baseline up to approximately 3 years (detailed time frame provided in description)
description: Cycles 1, 2, 3, 4, 6, 8, and then every 6 cycles, Day 1 of any intrapatient dose escalation, and at Treatment Discontinuation Visit
arm group label: Arm A Flat Dose Escalation: RO7297089
arm group type: Experimental
description: Participants in Arm A will receive the target dose of RO7297089 as a flat dose at each scheduled study drug administration visit
arm group label: Arm B Split Dose Escalation: RO7297089
arm group type: Experimental
description: Participants in Arm B will receive the first target dose of RO7297089 as a split dose divided over two days (Days 1 and 2). The full target dose will be administered at subsequent study drug administration visits.
arm group label: Arm C Step Dose Escalation: RO7297089
arm group type: Experimental
description: Participants in Arm C will receive the first cycle of RO7297089 as a single-step dose escalation. The Cycle 1 Day 1 dose will be lower than the target dose. The full target dose will be administered at subsequent study drug administration visits.
arm group label: Phase I Expansion Stage: RO7297089
arm group type: Experimental
description: After dose escalation has been completed, approximately 30 patients will be enrolled in the expansion stage. Participants will receive RO7297089 at the recommended phase 2 dose (at or below the maximum tolerated dose).
intervention type: Drug
intervention name: RO7297089
description: RO7297089 will be given via intravenous (IV) infusion
arm group label: Arm A Flat Dose Escalation: RO7297089
arm group label: Arm B Split Dose Escalation: RO7297089
arm group label: Arm C Step Dose Escalation: RO7297089
arm group label: Phase I Expansion Stage: RO7297089
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
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Belgium
country: Denmark
country: Norway
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
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)
submitted: February 23, 2023