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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) (FUSION-MM-005)

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ClinicalTrials.gov Identifier: NCT03000452
Recruitment Status : Completed
First Posted : December 22, 2016
Results First Posted : October 16, 2018
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Interventions Drug: DARATUMUMAB
Drug: DURVALUMAB
Enrollment 18
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
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.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Period Title: Treatment Period
Started 18
Completed 0
Not Completed 18
Reason Not Completed
Death             1
Progressive Disease (PD)             14
Physician Decision             1
Miscellaneous             2
Period Title: Follow-Up Period
Started 17 [1]
Completed 10
Not Completed 7
Reason Not Completed
Study Terminated by Sponsor             1
Death             3
Withdrawal by Subject             3
[1]
1 participant died in Cycle 1 due to PD prior to evaluation.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Baseline Participants 18
Hide Baseline Analysis Population Description
Full Analysis Population = all participants who enrolled in the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 18 participants
62.8  (11.41)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Female
11
  61.1%
Male
7
  38.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Black or African American
1
   5.6%
White
15
  83.3%
Not Collected or Reported
2
  11.1%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
0 = Fully Active
12
  66.7%
1 = Restrictive but ambulatory
5
  27.8%
2 = Ambulatory but unable to work
1
   5.6%
3 = Limited Self-Care
0
   0.0%
[1]
Measure 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 >50% of waking hours 4 = Completely Disabled, cannot carry on any self-care 5 = Dead
International Staging System Multiple Myeloma Stage at Entry   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 18 participants
Stage I
5
  27.8%
Stage II
4
  22.2%
Stage III
9
  50.0%
Missing
0
   0.0%
[1]
Measure 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.
Number of Prior Regimens  
Median (Full Range)
Unit of measure:  Regimens
Number Analyzed 18 participants
4.5
(3 to 16)
1.Primary Outcome
Title Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set = all participants who enrolled in the study.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: percentage of participants
0.0
2.Secondary Outcome
Title Time-to-Response (TTR)
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Duration of Response (DOR)
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Progression Free Survival
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Overall Survival
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*μg/L
3145469.40
(43.3%)
7.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC-inf) of Durvalumab
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: day*μg/L
5634957.81
(86.8%)
8.Secondary Outcome
Title Maximum Observed Concentration (Cmax) Of Durvalumab
Hide Description Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: μg/L
349391.46
(32.2%)
9.Secondary Outcome
Title Time to Reach Maximum Concentration (Tmax) of Durvalumab
Hide Description Time to Cmax, obtained directly from the observed concentration versus time data.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 14
Median (Full Range)
Unit of Measure: days
0.0476
(0.003 to 0.058)
10.Secondary Outcome
Title Terminal Half-Life (T1/2) of of Durvalumab
Hide 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.
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK Durvalumab profiles.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: days
15.71
(75.4%)
11.Secondary Outcome
Title Apparent Total Clearance (CL/F) of of Durvalumab
Hide Description Apparent total clearance, calculated as [Dose/AUCinf].
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L/day
0.27
(86.8%)
12.Secondary Outcome
Title Apparent Volume of Distribution (Vz/F) of Durvalumab
Hide Description Apparent volume of distribution, calculated as [(CL/F)/λz].
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.
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 10
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Liters
5.48
(25.1%)
13.Secondary Outcome
Title Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide 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.
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
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population consisted of all participants who received at least one dose of Durvalumab (Durva) or Daratumumab (Dara).
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
Overall Number of Participants Analyzed 18
Measure Type: Count of Participants
Unit of Measure: Participants
TEAE
18
 100.0%
TEAE Related to Durva
1
   5.6%
TEAE Related to Dara
4
  22.2%
TEAE Related to Durva or Dara
4
  22.2%
TEAE with CTCAE Grade (Gr) 3-4
11
  61.1%
TEAE with CTCAE Grade 3-4 Related to Durva
1
   5.6%
TEAE with CTCAE Grade 3-4 Related to Dara
2
  11.1%
TEAE with CTCAE Gr 3-4 Related to Durva or Dara
2
  11.1%
TEAE with CTCAE Grade 5
4
  22.2%
TEAE with CTCAE Grade 5 Related to Durva
0
   0.0%
TEAE with CTCAE Grade 5 Related to Dara
0
   0.0%
TEAE with CTCAE Gr 5 Related to Durva or Dara
0
   0.0%
Serious AE
7
  38.9%
Serious AE Related to Durva
0
   0.0%
Serious AE Related to Dara
0
   0.0%
Serious AE Related to Durva or Dara
0
   0.0%
TEAE leading to Interruption of Durva
1
   5.6%
TEAE leading to Interruption of Dara
1
   5.6%
TEAE leading to Interruption of Durva or Dara
1
   5.6%
TEAE interruption of Durva-without infusion delay
1
   5.6%
TEAE interruption of Dara-without infusion delay
1
   5.6%
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
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Daratumumab and Durvalumab
Hide Arm/Group 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.
All-Cause Mortality
Daratumumab and Durvalumab
Affected / at Risk (%)
Total   4/18 (22.22%) 
Hide Serious Adverse Events
Daratumumab and Durvalumab
Affected / at Risk (%)
Total   7/18 (38.89%) 
Cardiac disorders   
Cardiac failure  1  1/18 (5.56%) 
General disorders   
General physical health deterioration  1  4/18 (22.22%) 
Pyrexia  1  1/18 (5.56%) 
Infections and infestations   
Pneumonia  1  1/18 (5.56%) 
Renal and urinary disorders   
Acute kidney injury  1  1/18 (5.56%) 
Respiratory, thoracic and mediastinal disorders   
Pleural effusion  1  1/18 (5.56%) 
1
Term from vocabulary, MEDDRA V20.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Daratumumab and Durvalumab
Affected / at Risk (%)
Total   17/18 (94.44%) 
Blood and lymphatic system disorders   
Anaemia  1  12/18 (66.67%) 
Lymphopenia  1  1/18 (5.56%) 
Neutropenia  1  3/18 (16.67%) 
Thrombocytopenia  1  7/18 (38.89%) 
Cardiac disorders   
Tachycardia  1  1/18 (5.56%) 
Eye disorders   
Cataract  1  1/18 (5.56%) 
Gastrointestinal disorders   
Constipation  1  1/18 (5.56%) 
Diarrhoea  1  1/18 (5.56%) 
Nausea  1  2/18 (11.11%) 
Vomiting  1  1/18 (5.56%) 
General disorders   
Asthenia  1  1/18 (5.56%) 
Chest discomfort  1  1/18 (5.56%) 
Fatigue  1  9/18 (50.00%) 
General physical health deterioration  1  2/18 (11.11%) 
Localised oedema  1  1/18 (5.56%) 
Oedema peripheral  1  1/18 (5.56%) 
Pain  1  1/18 (5.56%) 
Pyrexia  1  3/18 (16.67%) 
Infections and infestations   
Herpes zoster  1  1/18 (5.56%) 
Respiratory tract infection  1  1/18 (5.56%) 
Upper respiratory tract infection  1  1/18 (5.56%) 
Viral upper respiratory tract infection  1  1/18 (5.56%) 
Investigations   
Alanine aminotransferase increased  1  1/18 (5.56%) 
Amylase increased  1  1/18 (5.56%) 
Aspartate aminotransferase increased  1  1/18 (5.56%) 
Blood creatinine increased  1  6/18 (33.33%) 
Blood fibrinogen decreased  1  1/18 (5.56%) 
Lipase increased  1  1/18 (5.56%) 
Weight decreased  1  3/18 (16.67%) 
Metabolism and nutrition disorders   
Decreased appetite  1  3/18 (16.67%) 
Hypercalcaemia  1  2/18 (11.11%) 
Hyperuricaemia  1  3/18 (16.67%) 
Hyponatraemia  1  1/18 (5.56%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  2/18 (11.11%) 
Back pain  1  2/18 (11.11%) 
Bone pain  1  5/18 (27.78%) 
Muscle spasms  1  1/18 (5.56%) 
Musculoskeletal pain  1  1/18 (5.56%) 
Neck pain  1  1/18 (5.56%) 
Pain in extremity  1  1/18 (5.56%) 
Pathological fracture  1  1/18 (5.56%) 
Nervous system disorders   
Neuralgia  1  1/18 (5.56%) 
Somnolence  1  1/18 (5.56%) 
Tremor  1  1/18 (5.56%) 
Psychiatric disorders   
Anxiety  1  1/18 (5.56%) 
Depression  1  1/18 (5.56%) 
Disorientation  1  1/18 (5.56%) 
Renal and urinary disorders   
Acute kidney injury  1  1/18 (5.56%) 
Haematuria  1  1/18 (5.56%) 
Respiratory, thoracic and mediastinal disorders   
Catarrh  1  1/18 (5.56%) 
Cough  1  1/18 (5.56%) 
Dyspnoea  1  3/18 (16.67%) 
Dyspnoea exertional  1  1/18 (5.56%) 
Epistaxis  1  1/18 (5.56%) 
Vascular disorders   
Deep vein thrombosis  1  1/18 (5.56%) 
Hypertension  1  2/18 (11.11%) 
1
Term from vocabulary, MEDDRA V20.0
Indicates events were collected by systematic assessment
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).
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results from a center cannot be submitted for publication before results of multicenter study are published unless it is > 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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Anne McClain, Senior Manager, Clinical Trial Disclosure
Organization: Celgene Corporation
Phone: 888-260-1599
EMail: ClinicalTrialDisclosure@Celgene.com
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT03000452    
Other Study ID Numbers: MEDI4736-MM-005
First Submitted: December 19, 2016
First Posted: December 22, 2016
Results First Submitted: September 18, 2018
Results First Posted: October 16, 2018
Last Update Posted: October 16, 2018