<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/NCT03275103</url>
  </required_header>
  <id_info>
    <org_study_id>GO39775</org_study_id>
    <secondary_id>2018-001041-13</secondary_id>
    <secondary_id>2022-502053-34-00</secondary_id>
    <nct_id>NCT03275103</nct_id>
  </id_info>
  <brief_title>Dose-Escalation Study of Cevostamab in Participants With Relapsed or Refractory Multiple Myeloma (R/R MM)</brief_title>
  <official_title>An Open-Label, Multicenter, Phase I Trial Evaluating the Safety and Pharmacokinetics of Escalating Doses of Cevostamab (BFCR4350A) 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a phase I, multicenter, open-label, dose-escalation study of cevostamab administered&#xD;
      as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma&#xD;
      (R/R MM).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 19, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>Single Group 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)</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Dose-Limiting Toxicities (DLTs)</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), except for Cytokine release syndrome (CRS), which will be graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Cytokine release syndrome was recorded as an AE that generally occurs &gt;30 minutes after the start of Cevostamab administration and at any time afterward in a given cycle.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-Time Curve (AUC) of Cevostamab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the total exposure of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC of Tocilizumab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the total exposure of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Serum Concentration (Cmax) of Cevostamab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the maximum observed serum concentration of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of Tocilizumab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the maximum observed serum concentration of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Observed Serum Concentration (Cmin) of Cevostamab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the minimum observed serum concentration of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin of Tocilizumab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the minimum observed serum concentration of study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL) of Cevostamab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the volume of plasma cleared of the drug per unit time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL of Tocilizumab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the volume of plasma cleared of the drug per unit time.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of Distribution at Steady State (Vdss) of Cevostamab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vdss of Tocilizumab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of Cevostamab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum Concentration of Tocilizumab</measure>
    <time_frame>Up to approximately 8 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>ORR is defined as percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) .&#xD;
sCR is defined as CR (as defined below), plus: Normal FLC ratio and absence of clonal cells in bone marrow (BM) by immunohistochemistry (kappa/lambda ratio &lt;/=4:1 or &gt;/=1:2 for kappa and lambda participants, respectively after counting &gt;/=100 plasma cells).&#xD;
CR is defined as no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine, disappearance of any soft tissue plasmacytomas, and &lt;/= 5% plasma cells in BM.&#xD;
VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or &gt;/=90% reduction in serum M-protein plus urine M-protein level &lt;100 milligrams (mg)/24 hr.&#xD;
PR is defined as &gt;/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by &gt;/= 90% or to &lt; 200 mg/24 hours.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>Time from first occurrence of ORR (defined previously) to disease progression (PD) or death from any cause. PD: increase of &gt;/=25% from lowest response value in one of the following: serum M-protein (absolute increase &gt;/=0.5 grams per deciliter (g/dL); serum M-protein increase &gt;/=1g/dL, if lowest M component was &gt;/=5g/dL; urine M-protein (absolute increase &gt;/=200 mg/24 hours); no measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase &gt;10 mg/dL); no measurable serum and urine M-protein levels and no measurable disease by FLC: BM plasma cell % irrespective of baseline status (absolute % &gt;/=10%); new lesion(s) &gt;/=50% increase from lowest point in sum of the products of diameters of &gt; 1 lesion, or &gt;/=50% increase in longest diameter of a previous lesion &gt;1 centimeter (cm) in short axis; &gt;/=50% increase in circulating plasma cells (minimum 200 cells per microliter) if only measure of disease.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in the Presence Anti-Drug Antibodies (ADAs)</measure>
    <time_frame>Up to approximately 8 years</time_frame>
    <description>To evaluate the immune response to the study drug.</description>
  </secondary_outcome>
  <number_of_arms>11</number_of_arms>
  <enrollment type="Anticipated">420</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Arm A: Single Step Dose Escalation for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Double Step Dose Escalation for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C: Single Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm D: Double Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm E: Expansion Phase for Tocilizumab Pretreatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm F: Single Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm G: Double Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm H: Triple Step Dose Escalation for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Cycle 1, participants will receive 3 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 2-4, 8, and 9-11. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm I: Triple Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The triple step dose expansion stage of the study may use the dosing and assessment schedule from the triple step dose escalation arm in Cycle 1, based on data from Arm H.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm J: Expansion Phase for Tocilizumab Pretreatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm K: Compressed Double Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In Cycle 1, participants will receive 2 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 4, and 8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cevostamab</intervention_name>
    <description>Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.</description>
    <arm_group_label>Arm A: Single Step Dose Escalation for Cevostamab</arm_group_label>
    <arm_group_label>Arm B: Double Step Dose Escalation for Cevostamab</arm_group_label>
    <arm_group_label>Arm C: Single Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_label>Arm D: Double Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_label>Arm E: Expansion Phase for Tocilizumab Pretreatment</arm_group_label>
    <arm_group_label>Arm F: Single Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_label>Arm G: Double Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_label>Arm H: Triple Step Dose Escalation for Cevostamab</arm_group_label>
    <arm_group_label>Arm I: Triple Step Dose Expansion for Cevostamab</arm_group_label>
    <arm_group_label>Arm J: Expansion Phase for Tocilizumab Pretreatment</arm_group_label>
    <arm_group_label>Arm K: Compressed Double Step Dose Expansion for Cevostamab</arm_group_label>
    <other_name>BFCR4350A; RO7187797</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tocilizumab</intervention_name>
    <description>Tocilizumab will be administered as premedication during Cycle 1.</description>
    <arm_group_label>Arm E: Expansion Phase for Tocilizumab Pretreatment</arm_group_label>
    <arm_group_label>Arm J: Expansion Phase for Tocilizumab Pretreatment</arm_group_label>
    <other_name>Actemra/RoActemra</other_name>
  </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;
          -  Participants must have relapsed or refractory (R/R) multiple myeloma (MM) for which no&#xD;
             established therapy for MM is appropriate and available or be intolerant to those&#xD;
             established therapies&#xD;
&#xD;
          -  Adverse events from prior anti-cancer therapy resolved to Grade &lt; or = 1, except any&#xD;
             grade alopecia and/or peripheral sensory or motor neuropathy which must have resolved&#xD;
             to Grade &lt; or = 2&#xD;
&#xD;
          -  Measurable disease defined by laboratory test results&#xD;
&#xD;
          -  Female participants of childbearing age must agree to remain abstinent or use reliable&#xD;
             contraceptive methods during the treatment period, and at least 5 months after last&#xD;
             dose of study drug. Women must refrain from breastfeeding during the same period.&#xD;
&#xD;
          -  Male participants must agree to refrain from donating sperm, to abstain or use a&#xD;
             condom during the treatment period, and for at least 2 months after the last dose of&#xD;
             tocilizumab (if applicable).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to comply with protocol-mandated hospitalization and activities restrictions&#xD;
&#xD;
          -  Pregnant or breastfeeding, or planning to become pregnant during the study or within 5&#xD;
             months after the last dose of cevostamab or within 3 months after the last dose of of&#xD;
             tocilizumab (if applicable)&#xD;
&#xD;
          -  Prior use of any monoclonal antibody, radioimmunoconjugate, or antibody-drug conjugate&#xD;
             as anti-cancer therapy within 4 weeks before first 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 infusion&#xD;
&#xD;
          -  Prior treatment with chimeric antigen receptor (CAR) T-cell therapy within 12 weeks&#xD;
             before first cevostamab infusion&#xD;
&#xD;
          -  Known treatment-related, immune-mediated adverse events associated with prior&#xD;
             immunotherapeutic agents&#xD;
&#xD;
          -  Treatment with radiotherapy, any chemotherapeutic agent, or treatment with any other&#xD;
             anti-cancer agent (investigational or otherwise) within 4 weeks or 5 half-lives of the&#xD;
             drug, whichever is shorter, prior to first cevostamab infusion&#xD;
&#xD;
          -  Autologous stem cell transplantation (SCT) within 100 days prior to first infusion&#xD;
&#xD;
          -  Prior allogeneic SCT or solid organ transplantation&#xD;
&#xD;
          -  Absolute plasma cell count exceeding 500/micro L or 5% of the peripheral blood white&#xD;
             cells&#xD;
&#xD;
          -  History of autoimmune disease or of confirmed progressive multifocal&#xD;
             leukoencephalopathy&#xD;
&#xD;
          -  Known history of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation&#xD;
             syndrome (MAS)&#xD;
&#xD;
          -  History of severe allergic or anaphylactic reactions to monoclonal antibody therapy&#xD;
             (or recombinant antibody-related fusion proteins)&#xD;
&#xD;
          -  Patients with known history of amyloidosis (e.g., positive Congo Red stain or&#xD;
             equivalent in tissue biopsy)&#xD;
&#xD;
          -  Patients with lesions in proximity of vital organs that may develop sudden&#xD;
             decompensation/deterioration in the setting of a tumor flare&#xD;
&#xD;
          -  History of other malignancy that could affect compliance with the protocol or&#xD;
             interpretation of results&#xD;
&#xD;
          -  Current or past history of central nervous system (CNS) disease, or CNS involvement by&#xD;
             MM&#xD;
&#xD;
          -  Significant cardiovascular disease that may limit a patient's ability to adequately&#xD;
             respond to a CRS event&#xD;
&#xD;
          -  Symptomatic active pulmonary disease requiring supplemental oxygen&#xD;
&#xD;
          -  Within 14 days prior to first cevostamab infusion: known active bacterial, viral,&#xD;
             fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of&#xD;
             nail beds) at study enrollment, or any major episode of infection requiring treatment&#xD;
             with IV antibiotics within 4 weeks prior to first infusion&#xD;
&#xD;
          -  Positive and quantifiable Epstein-Barr virus (EBV) polymerase chain reaction (PCR) or&#xD;
             cytomegalovirus (CMV) PCR prior to first study treatment&#xD;
&#xD;
          -  Known or suspected chronic active EBV infection, acute or chronic hepatitis C virus&#xD;
             (HCV) infection&#xD;
&#xD;
          -  Positive serologic or PCR test results for acute or chronic hepatitis B virus (HBV)&#xD;
             infection&#xD;
&#xD;
          -  Recent major surgery within 4 weeks prior to first infusion&#xD;
&#xD;
          -  Human Immunodeficiency Virus (HIV) positive&#xD;
&#xD;
          -  Any episode of active, symptomatic COVID-19 infection, or requiring treatment with IV&#xD;
             antivirals for COVID-19 (not including COVID-19 primary prophylaxis) within 14 days,&#xD;
             prior to first study treatment&#xD;
&#xD;
          -  Administration of a live, attenuated vaccine within 4 weeks before first cevostamab&#xD;
             infusion or anticipation that such a live attenuated vaccine will be required during&#xD;
             the study&#xD;
&#xD;
          -  Received systemic immunosuppressive medications (including, but not limited to,&#xD;
             cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis&#xD;
             factor agents), with the exception of corticosteroid treatment &lt;=10 mg/day prednisone&#xD;
             or equivalent within 2 weeks prior to first dose of cevostamab and, if applicable,&#xD;
             tocilizumab premedication prior to first dose of cevostamab&#xD;
&#xD;
          -  History of illicit drug or alcohol abuse within 12 months prior to screening&#xD;
&#xD;
          -  Any medical condition or laboratory test abnormality that precludes the participant's&#xD;
             safe participation in and completion of the study, or which could affect compliance&#xD;
             with the protocol or interpretation of results&#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: GO39775 https://forpatients.roche.com/</last_name>
    <phone>888-662-6728 (U.S. only)</phone>
    <email>global-roche-genentech-trials@gene.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35249</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Hospital - Arizona</name>
      <address>
        <city>Scottsdale</city>
        <state>Arizona</state>
        <zip>85259</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <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>University of California San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94117</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Mount Sinai Hospital</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10029-6574</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</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>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030-4009</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Alfred Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3004</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Center</name>
      <address>
        <city>North Melbourne</city>
        <state>Victoria</state>
        <zip>3051</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Calgary</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Cancer Center</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5G 1Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Jewish General Hospital</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3T 1E2</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
  </location>
  <location>
    <facility>
      <name>Clinica Universidad 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 Clinico Universitario de Salamanca; Servicio de Oncologia</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</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>
  <removed_countries>
    <country>Germany</country>
  </removed_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</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>Multiple Myeloma</mesh_term>
    <mesh_term>Neoplasms, Plasma Cell</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/ourmember/roche/). 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/NCT03275103
org study id: GO39775
secondary id: 2018-001041-13
secondary id: 2022-502053-34-00
nct id: NCT03275103
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a phase I, multicenter, open-label, dose-escalation study of cevostamab administered
      as a single agent by IV infusion to participants with relapsed or refractory multiple myeloma
      (R/R MM).
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants with Adverse Events (AEs)
time frame: Up to approximately 8 years
description: An AE is any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure that may or may not be considered related to the medical treatment or procedure.
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
time frame: Up to approximately 8 years
description: Dose-Limiting Toxicities (DLTs) will be reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI CTCAE v4.0), except for Cytokine release syndrome (CRS), which will be graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) Consensus Grading for Cytokine Release Syndrome.
measure: Arms E and J Only: Incidence and Severity of Cytokine-release Syndrome (CRS) Following Tocilizumab Premedication Followed by Treatment with Cevostamab
time frame: Up to approximately 8 years
description: Cytokine release syndrome was recorded as an AE that generally occurs >30 minutes after the start of Cevostamab administration and at any time afterward in a given cycle.
measure: Area Under the Concentration-Time Curve (AUC) of Cevostamab
time frame: Up to approximately 8 years
description: Defined as the total exposure of study drug.
measure: AUC of Tocilizumab
time frame: Up to approximately 8 years
description: Defined as the total exposure of study drug.
measure: Maximum Observed Serum Concentration (Cmax) of Cevostamab
time frame: Up to approximately 8 years
description: Defined as the maximum observed serum concentration of study drug.
measure: Cmax of Tocilizumab
time frame: Up to approximately 8 years
description: Defined as the maximum observed serum concentration of study drug.
measure: Minimum Observed Serum Concentration (Cmin) of Cevostamab
time frame: Up to approximately 8 years
description: Defined as the minimum observed serum concentration of study drug.
measure: Cmin of Tocilizumab
time frame: Up to approximately 8 years
description: Defined as the minimum observed serum concentration of study drug.
measure: Clearance (CL) of Cevostamab
time frame: Up to approximately 8 years
description: Defined as the volume of plasma cleared of the drug per unit time.
measure: CL of Tocilizumab
time frame: Up to approximately 8 years
description: Defined as the volume of plasma cleared of the drug per unit time.
measure: Volume of Distribution at Steady State (Vdss) of Cevostamab
time frame: Up to approximately 8 years
description: Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.
measure: Vdss of Tocilizumab
time frame: Up to approximately 8 years
description: Defined as the actual blood and tissue volume into which a drug is distributed and the relative binding of drug to protein in these spaces.
measure: Serum Concentration of Cevostamab
time frame: Up to approximately 8 years
measure: Serum Concentration of Tocilizumab
time frame: Up to approximately 8 years
measure: Objective Response Rate (ORR)
time frame: Up to approximately 8 years
description: ORR is defined as percentage of participants with stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) .
sCR is defined as CR (as defined below), plus: Normal FLC ratio and absence of clonal cells in bone marrow (BM) by immunohistochemistry (kappa/lambda ratio </=4:1 or >/=1:2 for kappa and lambda participants, respectively after counting >/=100 plasma cells).
CR is defined as no evidence of initial monoclonal protein isotype(s) on immunofixation of the serum and urine, disappearance of any soft tissue plasmacytomas, and </= 5% plasma cells in BM.
VGPR is defined as Serum and urine M-protein detectable by immunofixation but not on electrophoresis; or >/=90% reduction in serum M-protein plus urine M-protein level <100 milligrams (mg)/24 hr.
PR is defined as >/= 50% reduction of serum M-protein and reduction in 24-hour urine M-protein by >/= 90% or to < 200 mg/24 hours.
measure: Duration of Response
time frame: Up to approximately 8 years
description: Time from first occurrence of ORR (defined previously) to disease progression (PD) or death from any cause. PD: increase of >/=25% from lowest response value in one of the following: serum M-protein (absolute increase >/=0.5 grams per deciliter (g/dL); serum M-protein increase >/=1g/dL, if lowest M component was >/=5g/dL; urine M-protein (absolute increase >/=200 mg/24 hours); no measurable serum and urine M-protein levels: difference between involved and uninvolved free light chain (FLC) levels (absolute increase >10 mg/dL); no measurable serum and urine M-protein levels and no measurable disease by FLC: BM plasma cell % irrespective of baseline status (absolute % >/=10%); new lesion(s) >/=50% increase from lowest point in sum of the products of diameters of > 1 lesion, or >/=50% increase in longest diameter of a previous lesion >1 centimeter (cm) in short axis; >/=50% increase in circulating plasma cells (minimum 200 cells per microliter) if only measure of disease.
measure: Change from Baseline in the Presence Anti-Drug Antibodies (ADAs)
time frame: Up to approximately 8 years
description: To evaluate the immune response to the study drug.
arm group label: Arm A: Single Step Dose Escalation for Cevostamab
arm group type: Experimental
description: Study drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
arm group label: Arm B: Double Step Dose Escalation for Cevostamab
arm group type: Experimental
description: In Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
arm group label: Arm C: Single Step Dose Expansion for Cevostamab
arm group type: Experimental
description: The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.
arm group label: Arm D: Double Step Dose Expansion for Cevostamab
arm group type: Experimental
description: The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.
arm group label: Arm E: Expansion Phase for Tocilizumab Pretreatment
arm group type: Experimental
description: All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.
arm group label: Arm F: Single Step Dose Expansion for Cevostamab
arm group type: Experimental
description: The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.
arm group label: Arm G: Double Step Dose Expansion for Cevostamab
arm group type: Experimental
description: The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.
arm group label: Arm H: Triple Step Dose Escalation for Cevostamab
arm group type: Experimental
description: In Cycle 1, participants will receive 3 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 2-4, 8, and 9-11. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
arm group label: Arm I: Triple Step Dose Expansion for Cevostamab
arm group type: Experimental
description: The triple step dose expansion stage of the study may use the dosing and assessment schedule from the triple step dose escalation arm in Cycle 1, based on data from Arm H.
arm group label: Arm J: Expansion Phase for Tocilizumab Pretreatment
arm group type: Experimental
description: All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.
arm group label: Arm K: Compressed Double Step Dose Expansion for Cevostamab
arm group type: Experimental
description: In Cycle 1, participants will receive 2 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 4, and 8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.
intervention type: Drug
intervention name: Cevostamab
description: Cevostamab will be administered intravenously on a 21-day cycle, up to a total of 17 cycles.
arm group label: Arm A: Single Step Dose Escalation for Cevostamab
arm group label: Arm B: Double Step Dose Escalation for Cevostamab
arm group label: Arm C: Single Step Dose Expansion for Cevostamab
arm group label: Arm D: Double Step Dose Expansion for Cevostamab
arm group label: Arm E: Expansion Phase for Tocilizumab Pretreatment
arm group label: Arm F: Single Step Dose Expansion for Cevostamab
arm group label: Arm G: Double Step Dose Expansion for Cevostamab
arm group label: Arm H: Triple Step Dose Escalation for Cevostamab
arm group label: Arm I: Triple Step Dose Expansion for Cevostamab
arm group label: Arm J: Expansion Phase for Tocilizumab Pretreatment
arm group label: Arm K: Compressed Double Step Dose Expansion for Cevostamab
other name: BFCR4350A; RO7187797
intervention type: Drug
intervention name: Tocilizumab
description: Tocilizumab will be administered as premedication during Cycle 1.
arm group label: Arm E: Expansion Phase for Tocilizumab Pretreatment
arm group label: Arm J: Expansion Phase for Tocilizumab Pretreatment
other name: Actemra/RoActemra
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: GO39775 https://forpatients.roche.com/
phone: 888-662-6728 (U.S. only)
email: global-roche-genentech-trials@gene.com
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Withdrawn
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
facility: 
status: Recruiting
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
country: Germany
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
sharing ipd: No
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/ourmember/roche/). 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).