<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/NCT03000452</url>
  </required_header>
  <id_info>
    <org_study_id>MEDI4736-MM-005</org_study_id>
    <nct_id>NCT03000452</nct_id>
  </id_info>
  <brief_title>A Study to Determine the Efficacy of the Combination of Daratumumab (DARA) Plus Durvalumab (DURVA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)</brief_title>
  <acronym>FUSION-MM-005</acronym>
  <official_title>MEDI4736-MM-005 (FUSION MM-005): A Phase 2, Multicenter, Single-Arm, Study to Determine the Efficacy for the Combination of Durvalumab (DURVA) Plus Daratumumab (DARA) (D2) in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) That Have Progressed While on Current Treatment Regimen Containing Daratumumab.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celgene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celgene</source>
  <oversight_info>
    <has_dmc>Yes</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 single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of the&#xD;
      combination regimen of daratumumab plus durvalumab (D2). The study will consist of 2 parts;&#xD;
      Part 1 has a 2-stage design while Part 2 consists of an expansion phase. Subjects will&#xD;
      receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly [QW], every 2&#xD;
      weeks [Q2W] or every 4 weeks [Q4W] of each 28-day cycle) received on their last prior therapy&#xD;
      containing DARA. The dosing schedule for DARA may be adjusted during the course of the study&#xD;
      as outlined in the protocol. Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle&#xD;
      1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Indication:&#xD;
&#xD;
      This study will include subjects that have relapsed and refractory multiple myeloma (RRMM)&#xD;
      after treatment with at least 3 prior antimyeloma therapies, including a proteasome inhibitor&#xD;
      (PI) and an immunomodulatory drug (IMiD®) or after development of double-refractoriness to a&#xD;
      both a PI and an IMiD.&#xD;
&#xD;
      The most recent multiple myeloma (MM) treatment regimen should contain daratumumab (DARA) and&#xD;
      subjects must have progressed on DARA while on this regimen. Stage 1 A cohort of 18 subjects&#xD;
      will be enrolled to determine the preliminary efficacy of DARA plus DURVA. Once the 18&#xD;
      subjects have been enrolled, an interim analysis for futility purpose will be conducted to&#xD;
      determine if the study can proceed to Stage 2.&#xD;
&#xD;
      Early Safety Monitoring Once 6 subjects have been enrolled and completed the first treatment&#xD;
      cycle in Stage 1 of this study, the enrollment continuity would depend on the availability of&#xD;
      safety data from the on-going Phase 2 study (MEDI4736-MM-003) of DARA and DURVA in previously&#xD;
      DARA-naïve patients.&#xD;
&#xD;
        -  If MEDI4736-MM-003 safety data are available and the tolerability profile of DARA plus&#xD;
           DURVA has been determined to be adequate, then enrollment will continue as planned in&#xD;
           Stage 1 without an early safety monitoring review of the data.&#xD;
&#xD;
        -  If safety data are not available enrollment in this study will be paused for a review of&#xD;
           the safety profile of DARA plus DURVA by a Dose Review Team (DRT), using the data from&#xD;
           the first 6 patients.&#xD;
&#xD;
        -  If ≥ 1 of the first 6 patients experiences a dose-limiting toxicity (DLT), the study&#xD;
           will be halted for review and a change in the dosing regimen may be implemented.&#xD;
&#xD;
        -  The DRT will consist of the Celgene Medical Monitor, Celgene lead Safety Physician,&#xD;
           Celgene biostatistician, other Celgene functional area representatives, as appropriate,&#xD;
           study specific consultants (MD/PhD), and site investigator and/or designees who have&#xD;
           enrolled subjects to the study.&#xD;
&#xD;
        -  All available safety and, if applicable, PK/(pharmacodynamic) Pd, biomarker, and&#xD;
           preliminary efficacy data will be reviewed and can be considered in the DRT's decisions.&#xD;
&#xD;
        -  A DRT meeting will be held to review all data and make decisions regarding continuity of&#xD;
           the study.&#xD;
&#xD;
      Dose-limiting Toxicity&#xD;
&#xD;
      Dose-limiting toxicities (DLTs) may be evaluated during the DLT evaluation period for the&#xD;
      initial 6 patients in Part 1 of the study. The DLT evaluation period will be defined as the&#xD;
      first treatment cycle. Subjects are considered evaluable for assessment of DLT if they:&#xD;
&#xD;
        -  Receive at least 1 dose of study treatments and experience a DLT OR&#xD;
&#xD;
        -  Receive 1 dose of DURVA, 4 doses of DARA and complete the safety follow-up through the&#xD;
           end of the DLT evaluation period.&#xD;
&#xD;
      Grading of DLTs will be according to the National Cancer Institute Common Terminology&#xD;
      Criteria for Adverse Events (NCI CTCAE) Version 4.03.&#xD;
&#xD;
      A DLT will be defined as below:&#xD;
&#xD;
      Hematologic DLT&#xD;
&#xD;
        1. Grade 4 neutropenia observed for greater than 5 days duration&#xD;
&#xD;
        2. Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration.&#xD;
&#xD;
        3. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement&#xD;
           for platelets transfusion.&#xD;
&#xD;
        4. Any other Grade 4 hematologic toxicity that does not resolve to subject's pretreatment&#xD;
           baseline level within 72 hours&#xD;
&#xD;
        5. Grade 4 anemia, unexplained by underlying disease. Non-hematologic DLT&#xD;
&#xD;
      a. Any nonhematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by&#xD;
      medical management b. Any treatment interruption greater than 2 weeks due to an AE. While the&#xD;
      rules for adjudicating DLTs in the context of dose escalation are specified above, an AE not&#xD;
      listed above may be defined as a DLT after consultation with the Sponsor and investigators,&#xD;
      based on the emerging safety profile.&#xD;
&#xD;
      Stage 2 If 3 or more subjects achieved a response (PR or better) out of the 18 subjects at&#xD;
      the end of Stage 1, an additional 32 subjects will be enrolled to evaluate the safety and&#xD;
      efficacy of DARA plus DURVA.&#xD;
&#xD;
      Part 2: Expansion Upon completion of Part 1, if at least 9 subjects achieve a response (PR or&#xD;
      better) out of a total of 50 subjects and it is determined to further confirm the efficacy&#xD;
      and safety of DARA plus DURVA, an additional 70 subjects may be enrolled.&#xD;
&#xD;
      An Independent Response Adjudication Committee (IRAC) will be set up for this trial to review&#xD;
      study data. The IRAC will determine tumor response to therapy and to confirm the time of&#xD;
      disease progression (PD) (if disease progressed) at scheduled or unscheduled visits for each&#xD;
      subject.&#xD;
&#xD;
      The safety and efficacy of the study will be monitored by an independent Data Monitoring&#xD;
      Committee (DMC) who are not involved in the trial conduct. The DMC will meet up and review&#xD;
      study data at pre specified intervals throughout the trial.&#xD;
&#xD;
      In the event that the trial is halted for early safety monitoring, evaluation of the emerging&#xD;
      safety data from the initial 6 patients enrolled in Part 1 will be performed by the Dose&#xD;
      Review Team (DRT).&#xD;
&#xD;
      Safety data will be monitored by the Celgene Medical Monitor and Safety Physician on an&#xD;
      ongoing basis throughout the study. Should a significant safety issue be identified, the DMC&#xD;
      will be convened to make a recommendation as to the future conduct of the study.&#xD;
&#xD;
      The decision to discontinue a subject, which will not be delayed or refused by the Sponsor,&#xD;
      remains the responsibility of the treating physician. However, prior to discontinuing a&#xD;
      subject, the Investigator may contact the Medical Monitor and forward appropriate supporting&#xD;
      documents for review and discussion.&#xD;
&#xD;
      The study will be conducted in compliance with the International Council on Harmonisation&#xD;
      (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good&#xD;
      Clinical Practice (GCP) and applicable regulatory requirements.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 14, 2017</start_date>
  <completion_date type="Actual">December 4, 2017</completion_date>
  <primary_completion_date type="Actual">September 18, 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</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 an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria</measure>
    <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
    <description>Objective response is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the investigator assessment: sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level &lt; 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to &lt; 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time-to-Response (TTR)</measure>
    <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
    <description>Time-to-response was defined as the time from treatment initiation to the first documentation of response (PR or greater) based on IMWG criteria. sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level &lt;100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to &lt;200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
    <description>Duration of response was defined as time from the first documentation of response (PR or greater) to the first documentation of PD or death, whichever is earlier, based on the investigator assessments according to the IMWG Uniform Response Criteria.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
    <description>Progression free survival was defined as the time from treatment initiation to the first documentation of PD or death from any cause during study, whichever occurred earlier. Time to event analysis for PFS and was not analyzed due to insufficient follow up time because of early termination of the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
    <description>Overall Survival was defined as the time from treatment initiation to death due to any cause. Time to event analysis for overall survival was not analyzed due to insufficient follow up time because of early termination of the trial.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab</measure>
    <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
    <description>Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC-inf) of Durvalumab</measure>
    <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
    <description>Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Observed Concentration (Cmax) Of Durvalumab</measure>
    <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
    <description>Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Reach Maximum Concentration (Tmax) of Durvalumab</measure>
    <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
    <description>Time to Cmax, obtained directly from the observed concentration versus time data.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-Life (T1/2) of of Durvalumab</measure>
    <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
    <description>Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 was only calculated when a reliable estimate for λz could be obtained.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Total Clearance (CL/F) of of Durvalumab</measure>
    <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
    <description>Apparent total clearance, calculated as [Dose/AUCinf].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent Volume of Distribution (Vz/F) of Durvalumab</measure>
    <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
    <description>Apparent volume of distribution, calculated as [(CL/F)/λz].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>From the date of the first dose of study drug until 90 days after the last dose of durvalumab or daratumumab , whichever is later. Maximum overall time on treatment was 16 weeks for daratumumab and durvalumab</time_frame>
    <description>TEAEs include AEs between the earliest of the first dose date of either study drug and 90 days after the last dose of either study drug. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.03, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Multiple Myeloma</condition>
  <arm_group>
    <arm_group_label>Administration of Daratumumab (DARA) plus Durvalumab (DURVA)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle 1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle.&#xD;
Subjects will receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly [QW], every 2 weeks [Q2W], or every 4 weeks [Q4W] of each 28-day treatment cycle) received during their last prior therapy containing DARA at the time of DARA progression</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DARATUMUMAB</intervention_name>
    <description>DARATUMUMAB</description>
    <arm_group_label>Administration of Daratumumab (DARA) plus Durvalumab (DURVA)</arm_group_label>
    <other_name>DARA</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>DURVALUMAB</intervention_name>
    <description>DURVALUMAB</description>
    <arm_group_label>Administration of Daratumumab (DARA) plus Durvalumab (DURVA)</arm_group_label>
    <other_name>MEDI4736; DURVA</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects must satisfy the following criteria to be enrolled in the study:&#xD;
&#xD;
          1. Subject received at least 3 prior anti-myeloma regimens including a proteasome&#xD;
             inhibitor (PI) and an immunomodulatory agent or is double-refractory to a PI and an&#xD;
             immunomodulatory agent.&#xD;
&#xD;
               -  Induction, bone marrow transplant with or without maintenance therapy is&#xD;
                  considered one regimen.&#xD;
&#xD;
               -  Refractory is defined as disease that is nonresponsive on therapy, or progresses&#xD;
                  within 60 days of last therapy. Nonresponsive disease is defined as either&#xD;
                  failure to achieve minimal response or development of progressive disease while&#xD;
                  on therapy.&#xD;
&#xD;
               -  For subjects who received more than 1 regimen containing a PI their disease must&#xD;
                  be refractory to the most recent PI containing regimen.&#xD;
&#xD;
               -  For subjects who received more than 1 regimen containing a immunomodulatory agent&#xD;
                  their disease must be refractory to the most recent immunomodulatory agent&#xD;
                  containing regimen.&#xD;
&#xD;
          2. All subjects must have failed Daratumumab (DARA) either as a single agent or in&#xD;
             combination on last Multiple myeloma (MM) therapy. Failure is defined as disease&#xD;
             progression(PD) on DARA either as a single agent or in combination.&#xD;
&#xD;
          3. Subject has measurable disease defined as:&#xD;
&#xD;
               1. M-protein (serum protein electrophoresis (sPEP) or urine protein electrophoresis&#xD;
                  (uPEP): sPEP ≥ 0.5 g/dL or uPEP ≥ 200 mg/24 hours) and/or&#xD;
&#xD;
               2. Light chain MM without measurable disease in the serum or the urine: serum&#xD;
                  immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa&#xD;
                  lambda free light chain ratio&#xD;
&#xD;
          4. Subject achieved a response (minimal response [MR] or better) to at least 1 prior&#xD;
             treatment regimen.&#xD;
&#xD;
          5. Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status score of 2&#xD;
             or less.&#xD;
&#xD;
          6. Subject's toxicities resulting from previous therapy (including peripheral neuropathy)&#xD;
             have resolved or stabilized to ≤ Grade 1.&#xD;
&#xD;
          7. Subject is at least 18 years of age the time of signing the informed consent form&#xD;
             (ICF).&#xD;
&#xD;
          8. Subject must understand and voluntarily sign an ICF prior to any study-related&#xD;
             assessments/procedures being conducted.&#xD;
&#xD;
          9. Subject is willing and able to adhere to the study visit schedule and other protocol&#xD;
             requirements.&#xD;
&#xD;
         10. Females of childbearing potential (FCBP) must:&#xD;
&#xD;
             a. Have 2 negative pregnancy tests as verified by the investigator prior to starting&#xD;
             study treatment. This applies even if the subject practices true abstinence from&#xD;
             heterosexual contact.&#xD;
&#xD;
             i. Negative serum pregnancy test at screening ii. Negative serum or urine pregnancy&#xD;
             test (investigator's discretion) within 72 hours prior to starting study treatment&#xD;
             (Cycle 1, Day 1), and before beginning each subsequent cycle of treatment, and after&#xD;
             end of study treatment.&#xD;
&#xD;
             b. Either practice true abstinence from heterosexual contact (which must be reviewed&#xD;
             on a monthly basis and source documented) or agree to use, and be able to comply with,&#xD;
             effective contraception without interruption (eg, oral, inject able, or implantable&#xD;
             hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive&#xD;
             with spermicide; true abstinence; or vasectomized partner), 28 days prior to starting&#xD;
             study treatment, during the study therapy (including dose interruptions), and for at&#xD;
             least 90 days after discontinuation of study treatment.&#xD;
&#xD;
             c. Agree to abstain from breastfeeding during study participation and for at least 90&#xD;
             days after the last dose of Daratumumab (DARA) or Durvalumab (DURVA), whichever is&#xD;
             later.&#xD;
&#xD;
             d. Refrain from egg cell donation for at least 90 days after the final dose of DURVA&#xD;
             or DARA, whichever is later.&#xD;
&#xD;
         11. Male subjects must:&#xD;
&#xD;
               1. Either practice true abstinence (which must be reviewed on a monthly basis) or&#xD;
                  agree to use a condom during sexual contact with a pregnant female or a female of&#xD;
                  childbearing potential while participating in the study, during dose&#xD;
                  interruptions and for at least 90 days following study treatment discontinuation,&#xD;
                  even if he has undergone a successful vasectomy.&#xD;
&#xD;
               2. Refrain from sperm donation for at least 90 days after the final dose of DURVA or&#xD;
                  DARA, whichever is later.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The presence of any of the following will exclude a subject from enrollment:&#xD;
&#xD;
          1. Subject has had prior exposure to anti-CTLA-4, anti-PD-1 (Programmed cell death-1),&#xD;
             anti-PD-L1 (Programmed death-ligand 1) Monoclonal antibody (mAbs), or cancer vaccines&#xD;
&#xD;
          2. Subject has received autologous stem cell transplantation (ASCT) within 12 weeks&#xD;
             before the date of randomization.&#xD;
&#xD;
          3. History of organ or allogeneic stem cell transplantation&#xD;
&#xD;
          4. Subject received any of the following within the last 14 days of initiating study&#xD;
             treatment:&#xD;
&#xD;
               1. Plasmapheresis&#xD;
&#xD;
               2. Major surgery (as defined by the investigator)&#xD;
&#xD;
               3. Radiation therapy other than local therapy for myeloma associated bone lesions&#xD;
&#xD;
               4. Use of any systemic anti-myeloma drug therapy (except for DARA either alone or in&#xD;
                  combination with other agents given with it)&#xD;
&#xD;
          5. Subject received prior treatment with a monoclonal antibody within 5 half-lives of&#xD;
             initiating study treatment, other than DARA.&#xD;
&#xD;
          6. Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for&#xD;
             cancer treatment. Note: Concurrent use of hormones for noncancer-related conditions&#xD;
             (eg, insulin for diabetes and hormone replacement therapy) is acceptable.&#xD;
&#xD;
          7. Subject has any of the following laboratory abnormalities:&#xD;
&#xD;
               1. Absolute neutrophil count (ANC) &lt; 1,000/µL&#xD;
&#xD;
               2. Platelet count: &lt; 75,000/µL (it is not permissible to transfuse a subject to&#xD;
                  reach this level)&#xD;
&#xD;
               3. Hemoglobin &lt; 8 g/dL (&lt; 4.9 mmol/L) (it is not permissible to transfuse a subject&#xD;
                  to reach this level)&#xD;
&#xD;
               4. Creatinine clearance (CrCl) &lt; 45 mL/min (calculated using the Cockcroft-Gault&#xD;
                  formula or directly calculated from the 24-hour urine collection method)&#xD;
&#xD;
               5. Corrected serum calcium &gt; 13.5 mg/dL (&gt; 3.4 mmol/L)&#xD;
&#xD;
               6. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 2.5 ×&#xD;
                  upper limit of normal (ULN)&#xD;
&#xD;
               7. Serum total bilirubin &gt; 1.5 × upper limit of normal (ULN) or &gt; 3.0 mg/dL for&#xD;
                  subjects with documented Gilbert's syndrome&#xD;
&#xD;
          8. Subject has clinical evidence of central nervous system (CNS) or pulmonary&#xD;
             leukostasis, disseminated intravascular coagulation, or CNS MM&#xD;
&#xD;
          9. Subject has known chronic obstructive pulmonary disease (COPD) with a forced&#xD;
             expiratory volume in 1 second (FEV1) &lt; 50% of predicted normal. Note that forced&#xD;
             expiratory testing (FEV1) is required for subjects suspected of having COPD and&#xD;
             subjects must be excluded if FEV1 is &lt; 50% of predicted normal.&#xD;
&#xD;
         10. Subject has known moderate or severe persistent asthma within the past 2 years or&#xD;
             uncontrolled asthma of any classification. Note that subjects who currently have&#xD;
             controlled intermittent asthma or controlled mild persistent asthma are allowed to&#xD;
             participate in the study.&#xD;
&#xD;
         11. Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome&#xD;
             (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes),&#xD;
             or amyloidosis&#xD;
&#xD;
         12. Subject has nonsecretory MM&#xD;
&#xD;
         13. Subject has known allergy or hypersensitivity to study drug formulations&#xD;
&#xD;
         14. Subject has active or prior documented autoimmune or inflammatory disorders (including&#xD;
             inflammatory bowel disease [eg, colitis, Crohn's disease], diverticulitis, celiac&#xD;
             disease, irritable bowel disease, or other serious gastrointestinal chronic conditions&#xD;
             associated with diarrhea; systemic lupus erythematosus; Wegener syndrome; myasthenia&#xD;
             gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis, etc) within the&#xD;
             past 3 years prior to the start of treatment. The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
               1. Subjects with vitiligo or alopecia.&#xD;
&#xD;
               2. Subjects with hypothyroidism (eg, following Hashimoto's disease) stable on&#xD;
                  hormone replacement.&#xD;
&#xD;
               3. Psoriasis not requiring systemic treatment.&#xD;
&#xD;
         15. Subject has history of primary immunodeficiency&#xD;
&#xD;
         16. Subject is positive for human immunodeficiency virus (HIV-1), chronic or active&#xD;
             hepatitis B or active hepatitis A or C.&#xD;
&#xD;
         17. Subject has received live, attenuated vaccine within 30 days prior to the first dose&#xD;
             of DURVA (NOTE: Subjects, if enrolled, should not receive live vaccine during the&#xD;
             study and through 30 days after the last dose of DURVA)&#xD;
&#xD;
         18. Subject is currently using or has used immunosuppressive medication within 14 days&#xD;
             prior to the first study dose of study treatment. The following are exceptions to this&#xD;
             criterion:&#xD;
&#xD;
               1. Intranasal, topical, inhaled, or local steroid injections (eg, intra-articular&#xD;
                  injection).&#xD;
&#xD;
               2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of&#xD;
                  prednisone or equivalent.&#xD;
&#xD;
               3. Steroids as premedication for hypersensitivity reactions (eg, infusion-related&#xD;
                  reactions, computed tomography [CT] scan premedication).&#xD;
&#xD;
         19. Subject has any one of the following:&#xD;
&#xD;
               1. Clinically significant abnormal Electrocardiogram (ECG) finding at screening&#xD;
&#xD;
               2. Congestive heart failure (New York Heart Association Class III or IV)&#xD;
&#xD;
               3. Myocardial infarction within 12 months prior to starting study treatment&#xD;
&#xD;
               4. Unstable or poorly controlled angina pectoris, including Prinzmetal variant&#xD;
                  angina pectoris&#xD;
&#xD;
         20. Subject has prior history of malignancies, other than MM, unless the subject has been&#xD;
             free of the disease for ≥ 5 years with the exception of the following noninvasive&#xD;
             malignancies:&#xD;
&#xD;
               1. Basal cell carcinoma of the skin&#xD;
&#xD;
               2. Squamous cell carcinoma of the skin&#xD;
&#xD;
               3. Carcinoma in situ of the cervix&#xD;
&#xD;
               4. Carcinoma in situ of the breast&#xD;
&#xD;
               5. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM&#xD;
                  [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is&#xD;
                  curative&#xD;
&#xD;
         21. Subject is a female who is pregnant, nursing, or breastfeeding, or who intends to&#xD;
             become pregnant during the participation in the study.&#xD;
&#xD;
         22. Subject has any significant medical condition, laboratory abnormality, or psychiatric&#xD;
             illness that would prevent the subject from participating in the study&#xD;
&#xD;
         23. Subject has any condition including the presence of laboratory abnormalities, which&#xD;
             places the subject at unacceptable risk if he/she were to participate in the study&#xD;
&#xD;
         24. Subject has any condition that confounds the ability to interpret data from the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Steven Novick, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Celgene Corporation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>City of Hope Cancer Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010-300</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Center of Central Connecticut</name>
      <address>
        <city>Southington</city>
        <state>Connecticut</state>
        <zip>06489</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Parkview Research Center</name>
      <address>
        <city>Fort Wayne</city>
        <state>Indiana</state>
        <zip>46845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indiana University Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202-528</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland School of Med</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201-1595</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Theurer Cancer Center at Hackensack University Medical Center</name>
      <address>
        <city>Hackensack</city>
        <state>New Jersey</state>
        <zip>07601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morristown Memorial Hosp</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07962</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OHSU</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitaetsklinik Innsbruck</name>
      <address>
        <city>Innsbruck</city>
        <zip>6020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Salzburger Landkliniken St. Johanns-Spital</name>
      <address>
        <city>Salzburg</city>
        <zip>5020</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universitat Wien</name>
      <address>
        <city>Vienna</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexandra General Hospital of Athens</name>
      <address>
        <city>Athens</city>
        <zip>11528</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMCU Utrecht</name>
      <address>
        <city>Utrecht</city>
        <zip>3584 CX</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol Can Ruti</name>
      <address>
        <city>Badalona (Barcelona)</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de Salamanca</name>
      <address>
        <city>Salamanca</city>
        <zip>37007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Dr. Pesset</name>
      <address>
        <city>Valencia</city>
        <zip>46017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Falu lasarett</name>
      <address>
        <city>Falun SE</city>
        <zip>79182</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Helsingborg hospital</name>
      <address>
        <city>Helsingborg</city>
        <zip>254 37</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lund University Hosptial</name>
      <address>
        <city>Lund</city>
        <zip>22185</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karolinska University Hospital Huddinge</name>
      <address>
        <city>Stockholm</city>
        <zip>14186</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Greece</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Canada</country>
    <country>Germany</country>
    <country>Italy</country>
  </removed_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <results_first_submitted>September 18, 2018</results_first_submitted>
  <results_first_submitted_qc>September 18, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">October 16, 2018</results_first_posted>
  <last_update_submitted>September 18, 2018</last_update_submitted>
  <last_update_submitted_qc>September 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 16, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Multiple Myeloma</keyword>
  <keyword>Daratumumab</keyword>
  <keyword>Durvalumab</keyword>
  <keyword>Relapsed and Refractory Multiple Myeloma</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Durvalumab</mesh_term>
    <mesh_term>Daratumumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 3, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03000452/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 9, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/52/NCT03000452/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was conducted at 8 sites in 4 countries including Greece, Spain, Sweden and the United States, from 14 March 2017 to 04 December 2017</recruitment_details>
      <pre_assignment_details>Eligible participants included those with relapsed and refractory multiple myeloma (RRMM) who progressed on daratumumab (DARA) while on a DARA-containing regimen as the most recent multiple myeloma (MM) therapy. Participants had to have received at least 3 prior anti-myeloma therapies.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Daratumumab and Durvalumab</title>
          <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease (PD)</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Miscellaneous</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Follow-Up Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="17">1 participant died in Cycle 1 due to PD prior to evaluation.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study Terminated by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Full Analysis Population = all participants who enrolled in the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Daratumumab and Durvalumab</title>
          <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.8" spread="11.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Collected or Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)</title>
          <description>ECOG PS is used by physicians and researchers to assess how a subject's disease is progressing, and how the disease affects the daily living activities and determine appropriate treatment and prognosis. 0 = Fully Active, able to carry on all pre-disease performance without restriction; 1 = Restricted, in physically strenuous activity but ambulatory; 2 = Ambulatory and capable of all self-care; unable to carry out work activities. 3 = Capable of only limited self-care, confined to bed or chair &gt;50% of waking hours 4 = Completely Disabled, cannot carry on any self-care 5 = Dead</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>0 = Fully Active</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>1 = Restrictive but ambulatory</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>2 = Ambulatory but unable to work</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>3 = Limited Self-Care</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>International Staging System Multiple Myeloma Stage at Entry</title>
          <description>The International Staging System divides myeloma into 3 stages based only on the serum beta-2 microglobulin and serum albumin levels. Stage I: Serum beta-2 microglobulin is less than 3.5 (mg/L) and the albumin level is above 3.5 (g/L); Stage II: Neither stage I or III, meaning that either: # The beta-2 microglobulin level is between 3.5 and 5.5 (with any albumin level), OR # The albumin is below 3.5 while the beta-2 microglobulin is less than 3.5 Stage III: Serum beta-2 microglobulin is greater than 5.5.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Stage I</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage II</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stage III</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Number of Prior Regimens</title>
          <units>Regimens</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.5" lower_limit="3" upper_limit="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria</title>
        <description>Objective response is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the investigator assessment: sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level &lt; 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to &lt; 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.</description>
        <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
        <population>Full Analysis Set = all participants who enrolled in the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria</title>
          <description>Objective response is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the investigator assessment: sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level &lt; 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to &lt; 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.</description>
          <population>Full Analysis Set = all participants who enrolled in the study.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time-to-Response (TTR)</title>
        <description>Time-to-response was defined as the time from treatment initiation to the first documentation of response (PR or greater) based on IMWG criteria. sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level &lt;100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to &lt;200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.</description>
        <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
        <population>Analyses was not conducted for TTR due to no participant achieving a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee (DMC) the sponsor decided to close the study as the number of responses was not reached.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Time-to-Response (TTR)</title>
          <description>Time-to-response was defined as the time from treatment initiation to the first documentation of response (PR or greater) based on IMWG criteria. sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level &lt;100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to &lt;200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.</description>
          <population>Analyses was not conducted for TTR due to no participant achieving a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee (DMC) the sponsor decided to close the study as the number of responses was not reached.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Duration of Response (DOR)</title>
        <description>Duration of response was defined as time from the first documentation of response (PR or greater) to the first documentation of PD or death, whichever is earlier, based on the investigator assessments according to the IMWG Uniform Response Criteria.</description>
        <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
        <population>Analyses was not conducted for duration of response because no participant achieved a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee the sponsor decided to close the study as the number of responses was not reached.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Response (DOR)</title>
          <description>Duration of response was defined as time from the first documentation of response (PR or greater) to the first documentation of PD or death, whichever is earlier, based on the investigator assessments according to the IMWG Uniform Response Criteria.</description>
          <population>Analyses was not conducted for duration of response because no participant achieved a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee the sponsor decided to close the study as the number of responses was not reached.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression Free Survival</title>
        <description>Progression free survival was defined as the time from treatment initiation to the first documentation of PD or death from any cause during study, whichever occurred earlier. Time to event analysis for PFS and was not analyzed due to insufficient follow up time because of early termination of the trial.</description>
        <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
        <population>Analyses was not conducted for PFS because no participant achieved a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee the sponsor decided to close the study as the number of responses were not reached.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Progression Free Survival</title>
          <description>Progression free survival was defined as the time from treatment initiation to the first documentation of PD or death from any cause during study, whichever occurred earlier. Time to event analysis for PFS and was not analyzed due to insufficient follow up time because of early termination of the trial.</description>
          <population>Analyses was not conducted for PFS because no participant achieved a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee the sponsor decided to close the study as the number of responses were not reached.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival</title>
        <description>Overall Survival was defined as the time from treatment initiation to death due to any cause. Time to event analysis for overall survival was not analyzed due to insufficient follow up time because of early termination of the trial.</description>
        <time_frame>From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.</time_frame>
        <population>Analyses was not conducted for overall survival because no participant achieved a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee the sponsor decided to close the study as the number of responses was not reached.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival</title>
          <description>Overall Survival was defined as the time from treatment initiation to death due to any cause. Time to event analysis for overall survival was not analyzed due to insufficient follow up time because of early termination of the trial.</description>
          <population>Analyses was not conducted for overall survival because no participant achieved a best response better than stable disease in Stage 1 of the study. Following the review of the data by the data monitoring committee the sponsor decided to close the study as the number of responses was not reached.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab</title>
        <description>Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.</description>
        <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
        <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab</title>
          <description>Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.</description>
          <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
          <units>day*μg/L</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3145469.40" spread="43.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC-inf) of Durvalumab</title>
        <description>Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.</description>
        <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
        <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC-inf) of Durvalumab</title>
          <description>Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.</description>
          <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
          <units>day*μg/L</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5634957.81" spread="86.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Observed Concentration (Cmax) Of Durvalumab</title>
        <description>Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.</description>
        <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
        <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) Of Durvalumab</title>
          <description>Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.</description>
          <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
          <units>μg/L</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="349391.46" spread="32.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Reach Maximum Concentration (Tmax) of Durvalumab</title>
        <description>Time to Cmax, obtained directly from the observed concentration versus time data.</description>
        <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
        <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Reach Maximum Concentration (Tmax) of Durvalumab</title>
          <description>Time to Cmax, obtained directly from the observed concentration versus time data.</description>
          <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0476" lower_limit="0.003" upper_limit="0.058"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-Life (T1/2) of of Durvalumab</title>
        <description>Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 was only calculated when a reliable estimate for λz could be obtained.</description>
        <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
        <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK Durvalumab profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-Life (T1/2) of of Durvalumab</title>
          <description>Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 was only calculated when a reliable estimate for λz could be obtained.</description>
          <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK Durvalumab profiles.</population>
          <units>days</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.71" spread="75.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Total Clearance (CL/F) of of Durvalumab</title>
        <description>Apparent total clearance, calculated as [Dose/AUCinf].</description>
        <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
        <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Total Clearance (CL/F) of of Durvalumab</title>
          <description>Apparent total clearance, calculated as [Dose/AUCinf].</description>
          <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
          <units>L/day</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.27" spread="86.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Apparent Volume of Distribution (Vz/F) of Durvalumab</title>
        <description>Apparent volume of distribution, calculated as [(CL/F)/λz].</description>
        <time_frame>Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.</time_frame>
        <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution (Vz/F) of Durvalumab</title>
          <description>Apparent volume of distribution, calculated as [(CL/F)/λz].</description>
          <population>The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.</population>
          <units>Liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.48" spread="25.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>TEAEs include AEs between the earliest of the first dose date of either study drug and 90 days after the last dose of either study drug. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.03, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above.</description>
        <time_frame>From the date of the first dose of study drug until 90 days after the last dose of durvalumab or daratumumab , whichever is later. Maximum overall time on treatment was 16 weeks for daratumumab and durvalumab</time_frame>
        <population>The safety population consisted of all participants who received at least one dose of Durvalumab (Durva) or Daratumumab (Dara).</population>
        <group_list>
          <group group_id="O1">
            <title>Daratumumab and Durvalumab</title>
            <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>TEAEs include AEs between the earliest of the first dose date of either study drug and 90 days after the last dose of either study drug. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.03, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above.</description>
          <population>The safety population consisted of all participants who received at least one dose of Durvalumab (Durva) or Daratumumab (Dara).</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE Related to Durva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE Related to Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE Related to Durva or Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Grade (Gr) 3-4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Grade 3-4 Related to Durva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Grade 3-4 Related to Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Gr 3-4 Related to Durva or Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Grade 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Grade 5 Related to Durva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Grade 5 Related to Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE with CTCAE Gr 5 Related to Durva or Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious AE Related to Durva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious AE Related to Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious AE Related to Durva or Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to Interruption of Durva</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to Interruption of Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to Interruption of Durva or Dara</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE interruption of Durva-without infusion delay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE interruption of Dara-without infusion delay</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study drug to 90 days after the last dose of daratumumab and durvalumab, whichever was later, as well as SAEs made known to the investigator at any time thereafter that are suspected of being related to daratumumab or durvalumab. Maximum overall time on treatment was 16 weeks for daratumumab and durvalumab</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Daratumumab and Durvalumab</title>
          <description>Participants received intravenous daratumumab at 16 mg/kg on the same dosing schedule (weekly, every 2 weeks, or every 4 weeks of each 28-day treatment cycle) on their last prior therapy containing daratumumab regimen. The dosing schedule for daratumumab could be adjusted during the course of the study, provided the participant had a response of stable disease or better. Participants also received IV durvalumab at 1500 mg on Day 2 of Cycle 1 and then on Day 1 of Cycles ≥ 2 of each 28-day treatment cycle. Participants could continue on study treatment until progressive disease or unacceptable toxicity.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MEDDRA V20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MEDDRA V20.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Localised oedema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Herpes zoster</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Blood fibrinogen decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypercalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyperuricaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Disorientation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Catarrh</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Deep vein thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Results from a center cannot be submitted for publication before results of multicenter study are published unless it is &gt; 1 year since study completion. Then, Investigator can publish if manuscript is submitted to Celgene 60 days prior to submission. If Celgene decides publication would hinder drug development, Investigator must delay submission for up to 90 additional days. Investigator must delete confidential information before submission and defer publication to permit patent applications.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>An independent DMC reviewed data from Part 1 Stage 1 of the study on 26 Oct 2017; based on their recommendations, Celgene decided to close the study due to unfavorable efficacy results (number of responses to move to Stage 2 was not reached).</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Anne McClain, Senior Manager, Clinical Trial Disclosure</name_or_title>
      <organization>Celgene Corporation</organization>
      <phone>888-260-1599</phone>
      <email>ClinicalTrialDisclosure@Celgene.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03000452
org study id: MEDI4736-MM-005
nct id: NCT03000452
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of the
      combination regimen of daratumumab plus durvalumab (D2). The study will consist of 2 parts;
      Part 1 has a 2-stage design while Part 2 consists of an expansion phase. Subjects will
      receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly [QW], every 2
      weeks [Q2W] or every 4 weeks [Q4W] of each 28-day cycle) received on their last prior therapy
      containing DARA. The dosing schedule for DARA may be adjusted during the course of the study
      as outlined in the protocol. Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle
      1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle.
Indication:

      This study will include subjects that have relapsed and refractory multiple myeloma (RRMM)
      after treatment with at least 3 prior antimyeloma therapies, including a proteasome inhibitor
      (PI) and an immunomodulatory drug (IMiD®) or after development of double-refractoriness to a
      both a PI and an IMiD.

      The most recent multiple myeloma (MM) treatment regimen should contain daratumumab (DARA) and
      subjects must have progressed on DARA while on this regimen. Stage 1 A cohort of 18 subjects
      will be enrolled to determine the preliminary efficacy of DARA plus DURVA. Once the 18
      subjects have been enrolled, an interim analysis for futility purpose will be conducted to
      determine if the study can proceed to Stage 2.

      Early Safety Monitoring Once 6 subjects have been enrolled and completed the first treatment
      cycle in Stage 1 of this study, the enrollment continuity would depend on the availability of
      safety data from the on-going Phase 2 study (MEDI4736-MM-003) of DARA and DURVA in previously
      DARA-naïve patients.

        -  If MEDI4736-MM-003 safety data are available and the tolerability profile of DARA plus
           DURVA has been determined to be adequate, then enrollment will continue as planned in
           Stage 1 without an early safety monitoring review of the data.

        -  If safety data are not available enrollment in this study will be paused for a review of
           the safety profile of DARA plus DURVA by a Dose Review Team (DRT), using the data from
           the first 6 patients.

        -  If ≥ 1 of the first 6 patients experiences a dose-limiting toxicity (DLT), the study
           will be halted for review and a change in the dosing regimen may be implemented.

        -  The DRT will consist of the Celgene Medical Monitor, Celgene lead Safety Physician,
           Celgene biostatistician, other Celgene functional area representatives, as appropriate,
           study specific consultants (MD/PhD), and site investigator and/or designees who have
           enrolled subjects to the study.

        -  All available safety and, if applicable, PK/(pharmacodynamic) Pd, biomarker, and
           preliminary efficacy data will be reviewed and can be considered in the DRT's decisions.

        -  A DRT meeting will be held to review all data and make decisions regarding continuity of
           the study.

      Dose-limiting Toxicity

      Dose-limiting toxicities (DLTs) may be evaluated during the DLT evaluation period for the
      initial 6 patients in Part 1 of the study. The DLT evaluation period will be defined as the
      first treatment cycle. Subjects are considered evaluable for assessment of DLT if they:

        -  Receive at least 1 dose of study treatments and experience a DLT OR

        -  Receive 1 dose of DURVA, 4 doses of DARA and complete the safety follow-up through the
           end of the DLT evaluation period.

      Grading of DLTs will be according to the National Cancer Institute Common Terminology
      Criteria for Adverse Events (NCI CTCAE) Version 4.03.

      A DLT will be defined as below:

      Hematologic DLT

        1. Grade 4 neutropenia observed for greater than 5 days duration

        2. Grade 3 neutropenia associated with fever (≥ 38.5 °C) of any duration.

        3. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or any requirement
           for platelets transfusion.

        4. Any other Grade 4 hematologic toxicity that does not resolve to subject's pretreatment
           baseline level within 72 hours

        5. Grade 4 anemia, unexplained by underlying disease. Non-hematologic DLT

      a. Any nonhematological toxicity ≥ Grade 3 except for alopecia and nausea controlled by
      medical management b. Any treatment interruption greater than 2 weeks due to an AE. While the
      rules for adjudicating DLTs in the context of dose escalation are specified above, an AE not
      listed above may be defined as a DLT after consultation with the Sponsor and investigators,
      based on the emerging safety profile.

      Stage 2 If 3 or more subjects achieved a response (PR or better) out of the 18 subjects at
      the end of Stage 1, an additional 32 subjects will be enrolled to evaluate the safety and
      efficacy of DARA plus DURVA.

      Part 2: Expansion Upon completion of Part 1, if at least 9 subjects achieve a response (PR or
      better) out of a total of 50 subjects and it is determined to further confirm the efficacy
      and safety of DARA plus DURVA, an additional 70 subjects may be enrolled.

      An Independent Response Adjudication Committee (IRAC) will be set up for this trial to review
      study data. The IRAC will determine tumor response to therapy and to confirm the time of
      disease progression (PD) (if disease progressed) at scheduled or unscheduled visits for each
      subject.

      The safety and efficacy of the study will be monitored by an independent Data Monitoring
      Committee (DMC) who are not involved in the trial conduct. The DMC will meet up and review
      study data at pre specified intervals throughout the trial.

      In the event that the trial is halted for early safety monitoring, evaluation of the emerging
      safety data from the initial 6 patients enrolled in Part 1 will be performed by the Dose
      Review Team (DRT).

      Safety data will be monitored by the Celgene Medical Monitor and Safety Physician on an
      ongoing basis throughout the study. Should a significant safety issue be identified, the DMC
      will be convened to make a recommendation as to the future conduct of the study.

      The decision to discontinue a subject, which will not be delayed or refused by the Sponsor,
      remains the responsibility of the treating physician. However, prior to discontinuing a
      subject, the Investigator may contact the Medical Monitor and forward appropriate supporting
      documents for review and discussion.

      The study will be conducted in compliance with the International Council on Harmonisation
      (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use/Good
      Clinical Practice (GCP) and applicable regulatory requirements.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
time frame: From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.
description: Objective response is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the investigator assessment: sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
measure: Time-to-Response (TTR)
time frame: From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.
description: Time-to-response was defined as the time from treatment initiation to the first documentation of response (PR or greater) based on IMWG criteria. sCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level <100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to <200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
measure: Duration of Response (DOR)
time frame: From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.
description: Duration of response was defined as time from the first documentation of response (PR or greater) to the first documentation of PD or death, whichever is earlier, based on the investigator assessments according to the IMWG Uniform Response Criteria.
measure: Progression Free Survival
time frame: From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.
description: Progression free survival was defined as the time from treatment initiation to the first documentation of PD or death from any cause during study, whichever occurred earlier. Time to event analysis for PFS and was not analyzed due to insufficient follow up time because of early termination of the trial.
measure: Overall Survival
time frame: From randomization until the data cut-off date of 17 April 2018. The median duration of treatment for durvalumab and daratumumab was 7.9 weeks and 8.0 weeks respectively.
description: Overall Survival was defined as the time from treatment initiation to death due to any cause. Time to event analysis for overall survival was not analyzed due to insufficient follow up time because of early termination of the trial.
measure: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab
time frame: Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.
description: Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration, calculated by linear trapezoidal method when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.
measure: Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC-inf) of Durvalumab
time frame: Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.
description: Area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated as [AUCt + Ct/ λz]. Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If AUC %Extrap was ≥25%, AUC inf was not reported.
measure: Maximum Observed Concentration (Cmax) Of Durvalumab
time frame: Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.
description: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
measure: Time to Reach Maximum Concentration (Tmax) of Durvalumab
time frame: Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.
description: Time to Cmax, obtained directly from the observed concentration versus time data.
measure: Terminal Half-Life (T1/2) of of Durvalumab
time frame: Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.
description: Terminal phase half-life in plasma, calculated as [(ln 2)/λz]. t1/2 was only calculated when a reliable estimate for λz could be obtained.
measure: Apparent Total Clearance (CL/F) of of Durvalumab
time frame: Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.
description: Apparent total clearance, calculated as [Dose/AUCinf].
measure: Apparent Volume of Distribution (Vz/F) of Durvalumab
time frame: Pharmacokinetic samples were drawn on Cycle 1 on Day 2 (C1D2) pre-dose, at the end of the infusion, on Day 8 at 144 hour post dose, on Day 15 at 312 hours post dose and on Day 22 at 480 hours post C1D2 infusion.
description: Apparent volume of distribution, calculated as [(CL/F)/λz].
measure: Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: From the date of the first dose of study drug until 90 days after the last dose of durvalumab or daratumumab , whichever is later. Maximum overall time on treatment was 16 weeks for daratumumab and durvalumab
description: TEAEs include AEs between the earliest of the first dose date of either study drug and 90 days after the last dose of either study drug. In addition, an AE that occurred beyond the timeframe and was assessed by the doctor as possibly related to IP was considered to be treatment-emergent. Severity was assessed using National Cancer Institute Common Toxicity Terminology Criteria for AEs (NCI CTCAE) version 4.03, where 1= Mild; 2= Moderate; 3= Severe; 4= Life-threatening; 5= Death related to AE. Serious AEs resulted in death, were life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly, or resulted in a medical event that may have jeopardized the patient or required medical or surgical intervention to prevent one of the outcomes above.
arm group label: Administration of Daratumumab (DARA) plus Durvalumab (DURVA)
arm group type: Experimental
description: Subjects will also receive IV DURVA at 1500 mg on Day 2 (Cycle 1) and on Day 1 (Cycles ≥ 2) of each 28-day treatment cycle.
Subjects will receive intravenous (IV) DARA at 16 mg/kg on the same dosing schedule (weekly [QW], every 2 weeks [Q2W], or every 4 weeks [Q4W] of each 28-day treatment cycle) received during their last prior therapy containing DARA at the time of DARA progression
intervention type: Drug
intervention name: DARATUMUMAB
description: DARATUMUMAB
arm group label: Administration of Daratumumab (DARA) plus Durvalumab (DURVA)
other name: DARA
intervention type: Drug
intervention name: DURVALUMAB
description: DURVALUMAB
arm group label: Administration of Daratumumab (DARA) plus Durvalumab (DURVA)
other name: MEDI4736; DURVA
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steven Novick, MD, PhD
role: Study Director
affiliation: Celgene Corporation
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Greece
country: Netherlands
country: Spain
country: Sweden
country: United States
country: Canada
country: Germany
country: Italy
responsible party type: Sponsor
mesh term: Multiple Myeloma
mesh term: Neoplasms, Plasma Cell
mesh term: Durvalumab
mesh term: Daratumumab
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: An independent DMC reviewed data from Part 1 Stage 1 of the study on 26 Oct 2017; based on their recommendations, Celgene decided to close the study due to unfavorable efficacy results (number of responses to move to Stage 2 was not reached).
point of contact: 