<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/NCT03761108</url>
  </required_header>
  <id_info>
    <org_study_id>R5458-ONC-1826</org_study_id>
    <secondary_id>2018-003188-78</secondary_id>
    <nct_id>NCT03761108</nct_id>
  </id_info>
  <brief_title>Phase 1/2 Study of REGN5458 in Patients With Relapsed or Refractory Multiple Myeloma</brief_title>
  <acronym>LINKER-MM1</acronym>
  <official_title>Phase 1/2 FIH Study of REGN5458 (Anti-BCMA x Anti-CD3 Bispecific Antibody) in Patients With Relapsed or Refractory Multiple Myeloma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Regeneron Pharmaceuticals</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>
      The primary objectives of the study are:&#xD;
&#xD;
        -  In the phase 1 portion of the study: To assess the safety, tolerability, and&#xD;
           dose-limiting toxicities (DLTs) and to determine one or more recommended phase 2 dose&#xD;
           regimens (RP2DRs) of REGN5458 as monotherapy in patients with relapsed or refractory&#xD;
           multiple myeloma (MM)&#xD;
&#xD;
        -  In the phase 2 portion of the study for each cohort: To assess the anti-tumor activity&#xD;
           of REGN5458, as measured by objective response rate (ORR) and as determined by an&#xD;
           Independent Review Committee (IRC), in patients who have progressed on or after 3 prior&#xD;
           lines of therapy or who are triple-refractory (defined as refractory to a(n) proteasome&#xD;
           inhibitor (PI), immunomodulatory imide drug (IMiD), and anti-CD38 monoclonal antibody)&#xD;
&#xD;
             -  Applicable to the phase 2 Japan cohort only: In addition to the objectives in phase&#xD;
                2, the Japan cohort will also assess the safety, tolerability, DLTs, and&#xD;
                pharmacokinetics (PK) of different regimens of REGN5458 as a monotherapy in&#xD;
                Japanese patients.&#xD;
&#xD;
      The secondary objectives of the study are:&#xD;
&#xD;
      In the phase 1 dose escalation portion:&#xD;
&#xD;
        -  To assess the preliminary anti-tumor activity of REGN5458 as determined by the&#xD;
           investigator and measured by ORR, duration of response (DOR), progression-free survival&#xD;
           (PFS), rate of minimal residual disease (MRD) negative status, and overall survival (OS)&#xD;
&#xD;
        -  To evaluate the PK properties of REGN5458&#xD;
&#xD;
        -  To characterize the immunogenicity of REGN5458&#xD;
&#xD;
      In the phase 2 portion for each cohort:&#xD;
&#xD;
        -  To assess the anti-tumor activity of REGN5458 as measured by:&#xD;
&#xD;
             -  ORR, as determined by the investigator&#xD;
&#xD;
             -  DOR and PFS, as determined by an IRC and the investigator&#xD;
&#xD;
             -  Rate of MRD negative status&#xD;
&#xD;
             -  OS&#xD;
&#xD;
        -  To evaluate the effects of REGN5458 on health-related quality of life (HRQoL) and&#xD;
           patient-reported functions and symptoms&#xD;
&#xD;
        -  To evaluate the safety and tolerability of REGN5458&#xD;
&#xD;
        -  To evaluate the PK properties of REGN5458&#xD;
&#xD;
        -  To characterize the immunogenicity of REGN5458&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 23, 2019</start_date>
  <completion_date type="Anticipated">March 14, 2032</completion_date>
  <primary_completion_date type="Anticipated">June 15, 2023</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>Yes</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period</measure>
    <time_frame>Up to 28 days</time_frame>
    <description>In the phase 1 portion and Phase 2 portion for Japanese cohort only</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and severity of treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 portion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence and severity of adverse events of special interest (AESI)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 portion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion, as determined by blinded Independent Review Committee (IRC).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Concentrations of REGN5458 in serum over time</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion, for Japanese pcohort only</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Concentrations of REGN5458 in the serum over time</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 and phase 2 portions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence over time of anti-drug antibodies (ADAs) to REGN5458</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 and Phase 2 portions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) using the IMWG criteria</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 and Phase 2 portions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS) as measured using the IMWG criteria</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 and Phase 2 portions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of minimal residual disease (MRD) negative status using the IMWG criteria</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 and Phase 2 portions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 and Phase 2 portions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR as measured using the IMWG criteria</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 1 and Phase 2 portions, as determined by the Investigator</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion&#xD;
The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as &quot;not at all&quot; and 4 as &quot;very much.&quot;</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion&#xD;
The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion&#xD;
The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in patient-reported global health status/QoL per EORTC QLQ-C30</measure>
    <time_frame>Baseline up to Up to 5 years</time_frame>
    <description>In the phase 2 portion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of REGN5458 on general health status per EQ-5D-3L</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of TEAEs with REGN5458</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of AESIs with REGN5458</measure>
    <time_frame>Up to 5 years</time_frame>
    <description>In the phase 2 portion</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">309</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>REGN5458</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Phase 1: Cohorts of multiple REGN5458 dose levels Phase 2: Until disease progression or other discontinuation criterion is met</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>REGN5458</intervention_name>
    <description>Administered by intravenous (IV) infusion</description>
    <arm_group_label>REGN5458</arm_group_label>
    <other_name>linvoseltamab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1&#xD;
&#xD;
          -  Confirmed diagnosis of active Multiple Myeloma (MM) by International Myeloma Working&#xD;
             Group (IMWG) diagnostic criteria&#xD;
&#xD;
          -  Patients must have myeloma that is response-evaluable according to the 2016 IMWG&#xD;
             response criteria as defined in the protocol.&#xD;
&#xD;
          -  Phase 1 Dose Escalation: Patients with MM who have exhausted all therapeutic options&#xD;
             that are expected to provide meaningful clinical benefit, either through disease&#xD;
             relapse, treatment refractory disease or intolerance of the therapy and including&#xD;
             either:&#xD;
&#xD;
               1. Progression on or after at least 3 lines of therapy, or intolerance of therapy,&#xD;
                  including a proteasome inhibitor, an Immunomodulatory agent (IMiD), and an&#xD;
                  anti-CD38 antibody, OR&#xD;
&#xD;
               2. Progression on or after an anti-CD38 antibody and have disease that is &quot;double&#xD;
                  refractory&quot; to a proteasome inhibitor and an IMiD, or intolerance of therapy. The&#xD;
                  anti-CD38 antibody may have been administered alone or in combination with&#xD;
                  another agent such as a proteasome inhibitor (PI). Refractory disease is defined&#xD;
                  as lack of response or relapse within 60 days of last treatment.&#xD;
&#xD;
          -  Phase 2:&#xD;
&#xD;
               1. Progression on or after at least 3 prior lines of therapy including a(n) PI,&#xD;
                  IMiD, and anti-CD38 antibody, OR&#xD;
&#xD;
               2. Patients must be triple-refractory, defined as being refractory to prior&#xD;
                  treatment with at least 1 anti-CD38 antibody, a proteasome inhibitor, and an&#xD;
                  IMiD.&#xD;
&#xD;
        Refractory disease is defined as progression during treatment or within 60 days after&#xD;
        completion of therapy, or less than 25% response to therapy.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of plasma cell leukemia, primary systemic light-chain amyloidosis,&#xD;
             (excluding myeloma-associated amyloidosis), Waldenström macroglobulinemia&#xD;
             (lymphoplasmacytic lymphoma), or POEMS syndrome (polyneuropathy, organomegaly,&#xD;
             endocrinopathy, monoclonal protein, and skin changes)&#xD;
&#xD;
          -  Patients with known MM brain lesions or meningeal involvement&#xD;
&#xD;
          -  Cardiac ejection fraction &lt;40% by echocardiogram or multi-gated acquisition scan&#xD;
             (MUGA)&#xD;
&#xD;
          -  Prior treatment with BCMA-directed immunotherapies, including BCMA bispecific&#xD;
             antibodies and BiTEs, and BCMA CAR T cells. Note: BCMA antibody-drug conjugates are&#xD;
             not excluded&#xD;
&#xD;
          -  History of allogeneic stem cell transplantation at any time, or autologous stem cell&#xD;
             transplantation within 12 weeks of the start of study treatment&#xD;
&#xD;
        Note: Other protocol defined inclusion / exclusion criteria apply&#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 Trial Management</last_name>
    <role>Study Director</role>
    <affiliation>Regeneron Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Miami Hospital/Sylvester Comprehensive</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moffitt Cancer Center</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute of Emory University</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Melvin and Bren Simon Comprehensive Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Norton Cancer Institute</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Michigan Health System</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barbara Ann Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Icahn School of Medicine at Mount Sinai</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center, Herbert Irving Pavilion</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032-3729</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University, James Cancer Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health Science University OHSU</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Clinic</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Swedish Cancer Institute</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis Netwerk Antwerpen (ZNA)- Stuivenberg</name>
      <address>
        <city>Antwerp</city>
        <zip>2060</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Brussels</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinikum Essen</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Medicine Mainz</name>
      <address>
        <city>Mainz</city>
        <zip>55131</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Wurzburg</name>
      <address>
        <city>Würzburg</city>
        <zip>6 97080</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center</name>
      <address>
        <city>Goyang-si</city>
        <state>Gyeonggi-do</state>
        <zip>10408</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Soul National University Hospital Jongno-gu</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System Seodaemun-gu</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul St.Mary's Hospital, The Catholic University of Korea Seocho-gu</name>
      <address>
        <city>Seoul</city>
        <zip>137-701</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica universidad de Navarra unidad centrak de ensayos clinicos 7a 2a fase</name>
      <address>
        <city>Pamplona</city>
        <state>Navarre</state>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Sant Pau, Carrer de Sant Antoni Maria Claret, 167</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitary Hospital La Princesa Calle de Diego de Leon 62</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal M-607, km 9.100</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital 12 de Octubre Avda de Cordoba, s/n</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca Paseo de San Vicente 58-182</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Royal Marsden Hospital Downs Road Surrey</name>
      <address>
        <city>London</city>
        <zip>SM2 5PT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
    <country>Korea, Republic of</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>November 29, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 3, 2018</study_first_posted>
  <last_update_submitted>April 3, 2023</last_update_submitted>
  <last_update_submitted_qc>April 3, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Relapsed, Refractory</keyword>
  <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>All IPD that underlie results in a publication.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.</ipd_time_frame>
    <ipd_access_criteria>Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.</ipd_access_criteria>
    <ipd_url>https://vivli.org/</ipd_url>
  </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/NCT03761108
org study id: R5458-ONC-1826
secondary id: 2018-003188-78
nct id: NCT03761108
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objectives of the study are:

        -  In the phase 1 portion of the study: To assess the safety, tolerability, and
           dose-limiting toxicities (DLTs) and to determine one or more recommended phase 2 dose
           regimens (RP2DRs) of REGN5458 as monotherapy in patients with relapsed or refractory
           multiple myeloma (MM)

        -  In the phase 2 portion of the study for each cohort: To assess the anti-tumor activity
           of REGN5458, as measured by objective response rate (ORR) and as determined by an
           Independent Review Committee (IRC), in patients who have progressed on or after 3 prior
           lines of therapy or who are triple-refractory (defined as refractory to a(n) proteasome
           inhibitor (PI), immunomodulatory imide drug (IMiD), and anti-CD38 monoclonal antibody)

             -  Applicable to the phase 2 Japan cohort only: In addition to the objectives in phase
                2, the Japan cohort will also assess the safety, tolerability, DLTs, and
                pharmacokinetics (PK) of different regimens of REGN5458 as a monotherapy in
                Japanese patients.

      The secondary objectives of the study are:

      In the phase 1 dose escalation portion:

        -  To assess the preliminary anti-tumor activity of REGN5458 as determined by the
           investigator and measured by ORR, duration of response (DOR), progression-free survival
           (PFS), rate of minimal residual disease (MRD) negative status, and overall survival (OS)

        -  To evaluate the PK properties of REGN5458

        -  To characterize the immunogenicity of REGN5458

      In the phase 2 portion for each cohort:

        -  To assess the anti-tumor activity of REGN5458 as measured by:

             -  ORR, as determined by the investigator

             -  DOR and PFS, as determined by an IRC and the investigator

             -  Rate of MRD negative status

             -  OS

        -  To evaluate the effects of REGN5458 on health-related quality of life (HRQoL) and
           patient-reported functions and symptoms

        -  To evaluate the safety and tolerability of REGN5458

        -  To evaluate the PK properties of REGN5458

        -  To characterize the immunogenicity of REGN5458
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of dose-limiting toxicities (DLTs) from the first dose through the end of the DLT observation period
time frame: Up to 28 days
description: In the phase 1 portion and Phase 2 portion for Japanese cohort only
measure: Incidence and severity of treatment-emergent adverse events (TEAEs)
time frame: Up to 5 years
description: In the phase 1 portion
measure: Incidence and severity of adverse events of special interest (AESI)
time frame: Up to 5 years
description: In the phase 1 portion
measure: Objective response rate (ORR) as measured using the International Myeloma Working Group (IMWG) criteria
time frame: Up to 5 years
description: In the phase 2 portion, as determined by blinded Independent Review Committee (IRC).
measure: Concentrations of REGN5458 in serum over time
time frame: Up to 5 years
description: In the phase 2 portion, for Japanese pcohort only
measure: Concentrations of REGN5458 in the serum over time
time frame: Up to 5 years
description: In the phase 1 and phase 2 portions
measure: Incidence over time of anti-drug antibodies (ADAs) to REGN5458
time frame: Up to 5 years
description: In the phase 1 and Phase 2 portions
measure: Duration of response (DOR) using the IMWG criteria
time frame: Up to 5 years
description: In the phase 1 and Phase 2 portions
measure: Progression-free survival (PFS) as measured using the IMWG criteria
time frame: Up to 5 years
description: In the phase 1 and Phase 2 portions
measure: Rate of minimal residual disease (MRD) negative status using the IMWG criteria
time frame: Up to 5 years
description: In the phase 1 and Phase 2 portions
measure: Overall survival (OS)
time frame: Up to 5 years
description: In the phase 1 and Phase 2 portions
measure: ORR as measured using the IMWG criteria
time frame: Up to 5 years
description: In the phase 1 and Phase 2 portions, as determined by the Investigator
measure: Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)
time frame: Up to 5 years
description: In the phase 2 portion
The EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including global health status/quality of life, functional Scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea and vomiting, and pain), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much."
measure: Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per Quality of Life Questionnaire-Multiple Myeloma module 20 [QLQ-MY20])
time frame: Up to 5 years
description: In the phase 2 portion
The EORTC QLQ-MY20 is a self -administered instrument to assess QoL in persons with MM. This 20-item questionnaire measures the following domains: symptom scales, including disease symptoms (6 items) and symptoms related to side effects of treatment (10 items); function scale and future perspective (3 items); and body image (1 item). A high score represents a high level of symptoms or problems.
measure: Effects of REGN5458 on HRQOL and patient-reported symptoms and functioning per EuroQoL-5 Dimension-3 Level Scale [EQ-5D-3L])
time frame: Up to 5 years
description: In the phase 2 portion
The EQ-5D-3L is a self-administered generic standardized health status measure, consisting of an EQ-5D descriptive system and an EQ visual analog scale. The EQ-5D-3L descriptive system assesses 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated on a 3-level scale: no problems, some problems, and extreme problems. The EQ visual analog scale component is a vertical visual analog scale used by patients to rate their health.
measure: Change in patient-reported global health status/QoL per EORTC QLQ-C30
time frame: Baseline up to Up to 5 years
description: In the phase 2 portion
measure: Time to definitive deterioration in patient-reported global health status/QoL per EORTC QLQ-C30
time frame: Up to 5 years
description: In the phase 2 portion
measure: Effects of REGN5458 on general health status per EQ-5D-3L
time frame: Up to 5 years
description: In the phase 2 portion
measure: Effects of REGN5458 on patient-reported functions and symptoms per EORTC QLQ-C30
time frame: Up to 5 years
description: In the phase 2 portion
measure: Effects of REGN5458 on patient-reported functions and symptoms per QLQ-MY20
time frame: Up to 5 years
description: In the phase 2 portion
measure: Incidence and severity of TEAEs with REGN5458
time frame: Up to 5 years
description: In the phase 2 portion
measure: Incidence and severity of AESIs with REGN5458
time frame: Up to 5 years
description: In the phase 2 portion
arm group label: REGN5458
arm group type: Experimental
description: Phase 1: Cohorts of multiple REGN5458 dose levels Phase 2: Until disease progression or other discontinuation criterion is met
intervention type: Drug
intervention name: REGN5458
description: Administered by intravenous (IV) infusion
arm group label: REGN5458
other name: linvoseltamab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trial Management
role: Study Director
affiliation: Regeneron Pharmaceuticals
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country: Belgium
country: Germany
country: Korea, Republic of
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
sharing ipd: Yes
ipd description: All IPD that underlie results in a publication.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
ipd access criteria: Qualified researchers may request access to study documents (including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan) that support the methods and findings reported in a manuscript. Individual de-identified participant data will be made available once the indication has been approved by a regulatory body, if there is participant consent and there is not a reasonable likelihood of participant re-identification.
ipd url: https://vivli.org/