Trial Outcomes & Findings for 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) (NCT NCT03000452)

Last Updated: 2018-10-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

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.

Results posted on

2018-10-16

Participant Flow

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

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.

Participant milestones

Participant milestones
Measure	Daratumumab and Durvalumab 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.
Treatment Period STARTED	18
Treatment Period COMPLETED	0
Treatment Period NOT COMPLETED	18
Follow-Up Period STARTED	17
Follow-Up Period COMPLETED	10
Follow-Up Period NOT COMPLETED	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Daratumumab and Durvalumab 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.
Treatment Period Death	1
Treatment Period Progressive Disease (PD)	14
Treatment Period Physician Decision	1
Treatment Period Miscellaneous	2
Follow-Up Period Study Terminated by Sponsor	1
Follow-Up Period Death	3
Follow-Up Period Withdrawal by Subject	3

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Daratumumab and Durvalumab n=18 Participants 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.
Age, Continuous	62.8 Years STANDARD_DEVIATION 11.41 • n=93 Participants
Sex: Female, Male Female	11 Participants n=93 Participants
Sex: Female, Male Male	7 Participants n=93 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants
Race/Ethnicity, Customized Asian	0 Participants n=93 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=93 Participants
Race/Ethnicity, Customized White	15 Participants n=93 Participants
Race/Ethnicity, Customized Not Collected or Reported	2 Participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 = Fully Active	12 Participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 1 = Restrictive but ambulatory	5 Participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 2 = Ambulatory but unable to work	1 Participants n=93 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 3 = Limited Self-Care	0 Participants n=93 Participants
International Staging System Multiple Myeloma Stage at Entry Stage I	5 Participants n=93 Participants
International Staging System Multiple Myeloma Stage at Entry Stage II	4 Participants n=93 Participants
International Staging System Multiple Myeloma Stage at Entry Stage III	9 Participants n=93 Participants
International Staging System Multiple Myeloma Stage at Entry Missing	0 Participants n=93 Participants
Number of Prior Regimens	4.5 Regimens n=93 Participants

PRIMARY outcome

Timeframe: 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.

Population: Full Analysis Set = all participants who enrolled in the study.

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=18 Participants 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.
Percentage of Participants With an Objective Response According to International Myeloma Working Group (IMWG) Uniform Response Criteria	0.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

Population: The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.

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.

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=14 Participants 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.
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration Of Durvalumab	3145469.40 day*μg/L Geometric Coefficient of Variation 43.3

SECONDARY outcome

Population: The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.

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.

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=10 Participants 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.
Area Under the Plasma Concentration-time Curve From Time 0 to Extrapolated to Infinity (AUC-inf) of Durvalumab	5634957.81 day*μg/L Geometric Coefficient of Variation 86.8

SECONDARY outcome

Population: The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.

Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=14 Participants 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.
Maximum Observed Concentration (Cmax) Of Durvalumab	349391.46 μg/L Geometric Coefficient of Variation 32.2

SECONDARY outcome

Population: The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.

Time to Cmax, obtained directly from the observed concentration versus time data.

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=14 Participants 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.
Time to Reach Maximum Concentration (Tmax) of Durvalumab	0.0476 days Interval 0.003 to 0.058

SECONDARY outcome

Population: The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK Durvalumab profiles.

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.

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=10 Participants 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.
Terminal Half-Life (T1/2) of of Durvalumab	15.71 days Geometric Coefficient of Variation 75.4

SECONDARY outcome

Population: The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.

Apparent total clearance, calculated as \[Dose/AUCinf\].

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=10 Participants 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.
Apparent Total Clearance (CL/F) of of Durvalumab	0.27 L/day Geometric Coefficient of Variation 86.8

SECONDARY outcome

Population: The pharmacokinetic population included participants who received at least 1 dose of study medication and had evaluable plasma PK durvalumab profiles.

Apparent volume of distribution, calculated as \[(CL/F)/λz\].

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=10 Participants 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.
Apparent Volume of Distribution (Vz/F) of Durvalumab	5.48 Liters Geometric Coefficient of Variation 25.1

SECONDARY outcome

Timeframe: 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

Population: The safety population consisted of all participants who received at least one dose of Durvalumab (Durva) or Daratumumab (Dara).

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.

Outcome measures

Outcome measures
Measure	Daratumumab and Durvalumab n=18 Participants 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.
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE	18 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE Related to Durva	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE Related to Dara	4 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE Related to Durva or Dara	4 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Grade (Gr) 3-4	11 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Grade 3-4 Related to Durva	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Grade 3-4 Related to Dara	2 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Gr 3-4 Related to Durva or Dara	2 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Grade 5	4 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Grade 5 Related to Durva	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Grade 5 Related to Dara	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE with CTCAE Gr 5 Related to Durva or Dara	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Serious AE	7 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Serious AE Related to Durva	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Serious AE Related to Dara	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) Serious AE Related to Durva or Dara	0 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE leading to Interruption of Durva	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE leading to Interruption of Dara	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE leading to Interruption of Durva or Dara	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE interruption of Durva-without infusion delay	1 Participants
Participants With Treatment-Emergent Adverse Events (TEAEs) TEAE interruption of Dara-without infusion delay	1 Participants

Adverse Events

Daratumumab and Durvalumab

Serious events: 7 serious events

Other events: 17 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Daratumumab and Durvalumab n=18 participants at risk 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.
Cardiac disorders Cardiac failure	5.6% 1/18 • 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
General disorders General physical health deterioration	22.2% 4/18 • 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
General disorders Pyrexia	5.6% 1/18 • 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
Infections and infestations Pneumonia	5.6% 1/18 • 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
Renal and urinary disorders Acute kidney injury	5.6% 1/18 • 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
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.6% 1/18 • 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

Other adverse events

Other adverse events
Measure	Daratumumab and Durvalumab n=18 participants at risk 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.
Blood and lymphatic system disorders Anaemia	66.7% 12/18 • 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
Blood and lymphatic system disorders Lymphopenia	5.6% 1/18 • 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
Blood and lymphatic system disorders Neutropenia	16.7% 3/18 • 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
Blood and lymphatic system disorders Thrombocytopenia	38.9% 7/18 • 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
Cardiac disorders Tachycardia	5.6% 1/18 • 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
Eye disorders Cataract	5.6% 1/18 • 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
Gastrointestinal disorders Constipation	5.6% 1/18 • 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
Gastrointestinal disorders Diarrhoea	5.6% 1/18 • 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
Gastrointestinal disorders Nausea	11.1% 2/18 • 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
Gastrointestinal disorders Vomiting	5.6% 1/18 • 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
General disorders Asthenia	5.6% 1/18 • 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
General disorders Chest discomfort	5.6% 1/18 • 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
General disorders Fatigue	50.0% 9/18 • 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
General disorders General physical health deterioration	11.1% 2/18 • 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
General disorders Localised oedema	5.6% 1/18 • 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
General disorders Oedema peripheral	5.6% 1/18 • 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
General disorders Pain	5.6% 1/18 • 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
General disorders Pyrexia	16.7% 3/18 • 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
Infections and infestations Herpes zoster	5.6% 1/18 • 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
Infections and infestations Respiratory tract infection	5.6% 1/18 • 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
Infections and infestations Upper respiratory tract infection	5.6% 1/18 • 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
Infections and infestations Viral upper respiratory tract infection	5.6% 1/18 • 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
Investigations Alanine aminotransferase increased	5.6% 1/18 • 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
Investigations Amylase increased	5.6% 1/18 • 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
Investigations Aspartate aminotransferase increased	5.6% 1/18 • 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
Investigations Blood creatinine increased	33.3% 6/18 • 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
Investigations Blood fibrinogen decreased	5.6% 1/18 • 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
Investigations Lipase increased	5.6% 1/18 • 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
Investigations Weight decreased	16.7% 3/18 • 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
Metabolism and nutrition disorders Decreased appetite	16.7% 3/18 • 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
Metabolism and nutrition disorders Hypercalcaemia	11.1% 2/18 • 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
Metabolism and nutrition disorders Hyperuricaemia	16.7% 3/18 • 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
Metabolism and nutrition disorders Hyponatraemia	5.6% 1/18 • 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
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 2/18 • 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
Musculoskeletal and connective tissue disorders Back pain	11.1% 2/18 • 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
Musculoskeletal and connective tissue disorders Bone pain	27.8% 5/18 • 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
Musculoskeletal and connective tissue disorders Muscle spasms	5.6% 1/18 • 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
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.6% 1/18 • 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
Musculoskeletal and connective tissue disorders Neck pain	5.6% 1/18 • 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
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • 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
Musculoskeletal and connective tissue disorders Pathological fracture	5.6% 1/18 • 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
Nervous system disorders Neuralgia	5.6% 1/18 • 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
Nervous system disorders Somnolence	5.6% 1/18 • 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
Nervous system disorders Tremor	5.6% 1/18 • 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
Psychiatric disorders Anxiety	5.6% 1/18 • 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
Psychiatric disorders Depression	5.6% 1/18 • 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
Psychiatric disorders Disorientation	5.6% 1/18 • 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
Renal and urinary disorders Acute kidney injury	5.6% 1/18 • 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
Renal and urinary disorders Haematuria	5.6% 1/18 • 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
Respiratory, thoracic and mediastinal disorders Catarrh	5.6% 1/18 • 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
Respiratory, thoracic and mediastinal disorders Cough	5.6% 1/18 • 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
Respiratory, thoracic and mediastinal disorders Dyspnoea	16.7% 3/18 • 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
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.6% 1/18 • 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
Respiratory, thoracic and mediastinal disorders Epistaxis	5.6% 1/18 • 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
Vascular disorders Deep vein thrombosis	5.6% 1/18 • 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
Vascular disorders Hypertension	11.1% 2/18 • 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

Additional Information

Anne McClain, Senior Manager, Clinical Trial Disclosure

Celgene Corporation

Phone: 888-260-1599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER