Trial Outcomes & Findings for A Study of Durvalumab in Combination With Lenalidomide With and Without Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma (NCT NCT02685826)

Last Updated: 2023-10-06

Results Overview

A Dose Review Team (DRT) evaluated DLTs to determine the recommended dose (RD) of Durvalumab to use in the Expansion Period. A DLT was defined as: a. Grade 4 neutropenia for \>= 5 days. b. Grade 3 neutropenia associated with fever (≥ 38.5°C / 101.3°F) of any duration. c. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or platelets transfusion. d. Grade 4 hematologic toxicity that does not resolve to baseline level \<=72 hours. e. Grade 4 anemia, unexplained by underlying disease. f. Any nonhematologic toxicity Grade ≥ 3 except for alopecia and nausea. g. Treatment interruption \>= 2 weeks due to AE. If ≤ 1 of the 6 initial participants in each cohort experience a DLT during cycle 1, the RD was Durvalumab 1500 mg; If \>=2 of the 6 initial participants in any cohort experience a DLT during cycle 1, the maximum tolerated dose (MTD) was exceeded and the dose level of Durvalumab was de-escalated to 750 mg

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

56 participants

Primary outcome timeframe

First treatment cycle: Day 1 to Day 28

Results posted on

2023-10-06

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort A: High Risk, TNE High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Overall Study STARTED	25	10	21
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	25	10	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort A: High Risk, TNE High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Overall Study Adverse Event	2	0	1
Overall Study Progressive Disease	2	1	0
Overall Study Withdrawal by Subject	2	0	0
Overall Study Full Clinical Hold by FDA	19	9	20

Baseline Characteristics

Data was collected for Cohort C only.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort A: High Risk, TNE n=25 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=10 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=21 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.	Total n=56 Participants Total of all reporting groups
Age, Continuous	75.4 years STANDARD_DEVIATION 4.17 • n=25 Participants	72.5 years STANDARD_DEVIATION 5.25 • n=10 Participants	59.6 years STANDARD_DEVIATION 7.52 • n=21 Participants	68.98 years STANDARD_DEVIATION 9.33 • n=56 Participants
Age, Customized <=65 years	0 participants n=25 Participants	0 participants n=10 Participants	17 participants n=21 Participants	17 participants n=56 Participants
Age, Customized >65 years	25 participants n=25 Participants	10 participants n=10 Participants	4 participants n=21 Participants	39 participants n=56 Participants
Age, Customized <=75 years	12 participants n=25 Participants	7 participants n=10 Participants	20 participants n=21 Participants	39 participants n=56 Participants
Age, Customized >75 years	13 participants n=25 Participants	3 participants n=10 Participants	1 participants n=21 Participants	17 participants n=56 Participants
Sex: Female, Male Female	15 Participants n=25 Participants	0 Participants n=10 Participants	4 Participants n=21 Participants	19 Participants n=56 Participants
Sex: Female, Male Male	10 Participants n=25 Participants	10 Participants n=10 Participants	17 Participants n=21 Participants	37 Participants n=56 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=56 Participants
Race (NIH/OMB) Asian	1 Participants n=25 Participants	1 Participants n=10 Participants	0 Participants n=21 Participants	2 Participants n=56 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=56 Participants
Race (NIH/OMB) Black or African American	1 Participants n=25 Participants	0 Participants n=10 Participants	0 Participants n=21 Participants	1 Participants n=56 Participants
Race (NIH/OMB) White	21 Participants n=25 Participants	9 Participants n=10 Participants	17 Participants n=21 Participants	47 Participants n=56 Participants
Race (NIH/OMB) More than one race	0 Participants n=25 Participants	0 Participants n=10 Participants	0 Participants n=21 Participants	0 Participants n=56 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=25 Participants	0 Participants n=10 Participants	4 Participants n=21 Participants	6 Participants n=56 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active	7 Participants n=25 Participants	5 Participants n=10 Participants	13 Participants n=21 Participants	25 Participants n=56 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restrictive but ambulatory	14 Participants n=25 Participants	5 Participants n=10 Participants	8 Participants n=21 Participants	27 Participants n=56 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = ambulatory but unable to work	4 Participants n=25 Participants	0 Participants n=10 Participants	0 Participants n=21 Participants	4 Participants n=56 Participants
International Staging System (ISS) for MM at Diagnosis Stage I	2 Participants n=25 Participants	5 Participants n=10 Participants	3 Participants n=21 Participants	10 Participants n=56 Participants
International Staging System (ISS) for MM at Diagnosis Stage II	7 Participants n=25 Participants	5 Participants n=10 Participants	7 Participants n=21 Participants	19 Participants n=56 Participants
International Staging System (ISS) for MM at Diagnosis Stage III	13 Participants n=25 Participants	0 Participants n=10 Participants	11 Participants n=21 Participants	24 Participants n=56 Participants
International Staging System (ISS) for MM at Diagnosis Missing	3 Participants n=25 Participants	0 Participants n=10 Participants	0 Participants n=21 Participants	3 Participants n=56 Participants
High-Risk Cytogenetic Abnormalities at Baseline Yes	17 Participants n=25 Participants	0 Participants n=10 Participants	2 Participants n=21 Participants	19 Participants n=56 Participants
High-Risk Cytogenetic Abnormalities at Baseline No	8 Participants n=25 Participants	10 Participants n=10 Participants	19 Participants n=21 Participants	37 Participants n=56 Participants
Minimal Residual Disease (MRD) Status Positive	—	—	21 Participants n=21 Participants • Data was collected for Cohort C only.	21 Participants n=21 Participants • Data was collected for Cohort C only.
Minimal Residual Disease (MRD) Status Negative	—	—	0 Participants n=21 Participants • Data was collected for Cohort C only.	0 Participants n=21 Participants • Data was collected for Cohort C only.

PRIMARY outcome

Timeframe: First treatment cycle: Day 1 to Day 28

Population: Dose-Determining Population consists of all participants from the Safety Population of the Dose Determining Period who received at least one dose of Durvalumab. Cohort B's Dose-Determining Population was 7 participants as one was considered non-evaluable and was therefore replaced per protocol

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=6 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=7 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=6 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Participants With Dose-Limiting Toxicities (DLTs) During the Dose-Determining Timeframe (Day 1 - Day 28)	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 up to Week 84 (the longer of 90 days after discontinuing treatment with DURVA, or 28 days after the last dose of LEN or dex)

Population: Safety population. The Safety Population is defined as all enrolled subjects who receive at least 1 dose of the study medications.

An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A TEAE includes AEs between the first dose date of either study drug and 90 days after the last dose of study drug. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required) - Grade 3 = Severe (limitation in activity; medical intervention required) - Grade 4 = Life-threatening - Grade 5 = Death

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=25 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=10 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=21 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Participants With Treatment Emergent Adverse Events (TEAE) >= 1 TEAE	24 Participants	9 Participants	18 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 severity 3/4, related to LEN	11 Participants	8 Participants	4 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 severity 3/4, related to dex	5 Participants	2 Participants	NA Participants Dexamethasone not administered to Cohort C
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Grade 5 TEAE related to study drug	0 Participants	0 Participants	1 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 TEAE leading to discontinuation of study drug	3 Participants	0 Participants	1 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 leading to interruption of dex	9 Participants	3 Participants	NA Participants Dexamethasone not administered to Cohort C
Participants With Treatment Emergent Adverse Events (TEAE) >=1 treatment-related TEAE	22 Participants	8 Participants	17 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 related to DURVA	16 Participants	4 Participants	15 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 related to LEN	22 Participants	8 Participants	15 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 related to dex	16 Participants	6 Participants	NA Participants Dexamethasone not administered to Cohort C
Participants With Treatment Emergent Adverse Events (TEAE) >=1 TEAE of severity grade 3 or 4	19 Participants	8 Participants	7 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 severity 3/4, related to study drug	13 Participants	8 Participants	6 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 severity 3/4, related to DURVA	7 Participants	4 Participants	4 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Grade 5 TEAE (Death)	1 Participants	0 Participants	1 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Grade 5 TEAE related to DURVA	0 Participants	0 Participants	1 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Grade 5 TEAE related to LEN	0 Participants	0 Participants	0 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Grade 5 TEAE related to dex	0 Participants	0 Participants	NA Participants Dexamethasone not administered to Cohort C
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Serious TEAE	12 Participants	6 Participants	4 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Serious TEAE related to study drug	8 Participants	4 Participants	4 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Serious TEAE related to DURVA	5 Participants	1 Participants	4 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Serious TEAE related to LEN	6 Participants	3 Participants	2 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 Serious TEAE related to dex	5 Participants	1 Participants	NA Participants Dexamethasone not administered to Cohort C
Participants With Treatment Emergent Adverse Events (TEAE) >= TEAE leading to discontinuation of DURVA	2 Participants	0 Participants	1 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >= TEAE leading to discontinuation of LEN	3 Participants	0 Participants	0 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >= TEAE leading to discontinuation of dex	2 Participants	0 Participants	NA Participants Dexamethasone not administered to Cohort C
Participants With Treatment Emergent Adverse Events (TEAE) >=1 leading to delay/reduction/interruption drug	14 Participants	7 Participants	6 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 leading to dose delay of DURVA	10 Participants	3 Participants	4 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 leading to infusion interruption of DURVA	0 Participants	0 Participants	1 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 leading to dose reduction of LEN	2 Participants	2 Participants	3 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 leading to interruption of LEN	13 Participants	5 Participants	5 Participants
Participants With Treatment Emergent Adverse Events (TEAE) >=1 leading to dose reduction of dex	1 Participants	3 Participants	NA Participants Dexamethasone not administered to Cohort C

SECONDARY outcome

Timeframe: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)

Population: Efficacy Evaluable Population which consisted of enrolled participants who received at least 1 dose of the study medications and had at least 1 evaluable postbaseline response assessment. See the Response Improvement Rate outcome for an efficacy measure for Cohort C.

Tumor response, including progressive disease, was assessed by the investigators and captured the best assessment of response during the treatment period. ORR was defined as partial response (PR) or better which includes PR, very good partial response (VGPR), complete response (CR), or stringent complete response (sCR). A PR required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours. If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas was also required. sCR required - a negative immunofixation of serum and urine and - disappearance of any soft tissue plasmacytomas and - ≤ 5% plasma cells in bone marrow and normal free light-chain (FLC) ratio and - absence of clonal plasma cells by immunohistochemistry or 2- to 4-color flow cytometry.

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=24 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=10 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Overall Response Rate (ORR) for Cohorts A and B: Percentage of Participants Who Achieved a Partial Response or Better According to the International Myeloma Working Group (IMWG) Uniform Response Criteria	66.7 percentage of participants Interval 51.6 to 79.5	50.0 percentage of participants Interval 26.7 to 73.3	—

SECONDARY outcome

Timeframe: Baseline (Cycle 1 Day 1); Treatment: Day 1 of each cycle starting with Cycle 2 up to Cycle 15 plus one week for the end of treatment visit (Day 29 up to Week 61)

Population: Efficacy Evaluable Population which consists of all enrolled participants who received at least 1 dose of the study medications and had at least 1 evaluable postbaseline response assessment.

Response Improvement Rate is defined as the percentage of participants who achieved a response from treatment as compared to the pre-autologous stem cell transplantation \[ASCT\] diseases measurement used as baseline for response assessment. IMWG response categories could be stable disease (SD), partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), as long as it represented an improvement compared to prior to transplant.

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=21 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Response Improvement Rate (RIR) for Cohort C: Percentage of Participants Achieving a Response Improved From Cycle 1 Day 1 as Assessed by the Investigators Using the International Myeloma Working Group (IMWG) Uniform Response Criteria	—	—	0 percentage of participants not estimable for a value of zero

SECONDARY outcome

Timeframe: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)

Population: Efficacy Evaluable Population: Participants in Cohorts A + B who had a response

Time to response (for responders only, per IMWG Uniform Response Criteria) is calculated as the time from the first date of dosing of study medication to the first date of documented response (PR or better).

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=16 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=5 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Time to Response (for Cohorts A and B)	4.20 weeks Interval 3.9 to 23.1	4.10 weeks Interval 4.0 to 13.0	—

SECONDARY outcome

Timeframe: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)

Population: Efficacy Evaluable Population: Participants in Cohorts A + B who had a response.

Duration of response (for responders only) was defined as the time from earliest date of documented response (PR or better) to the earliest date of disease progression (DP) as determined by the investigator per IMWG Uniform Response criteria or death during study treatment, whichever occurred first.

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=16 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=5 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Kaplan-Meier Estimates for Duration of Response (for Cohort A and B)	10.3 months Interval 7.2 to not estimable since few responders had DP by the time the study was terminated	NA months not estimable since no responder had DP by the time the study was terminated	—

SECONDARY outcome

Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1

Population: The PK Population included participants who received \>=1 dose of study treatment and had \>=1 measurable PK assessment. If participants were noncompliant with respect to dosing, had incomplete data, or other circumstances that would affect PK evaluation, inclusion was made on a case-by-case basis.

Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100\*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=23 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=10 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=20 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Durvalumab (DURVA) Serum Pharmacokinetic (PK) Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)	3535033.014 day*µg/L Geometric Coefficient of Variation 39.8	3582905.960 day*µg/L Geometric Coefficient of Variation 21.0	4026520.655 day*µg/L Geometric Coefficient of Variation 39.1

SECONDARY outcome

Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=23 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=9 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=19 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)	4944601.671 day*µg/L Geometric Coefficient of Variation 60.9	5532568.144 day*µg/L Geometric Coefficient of Variation 62.5	6531541.670 day*µg/L Geometric Coefficient of Variation 36.4

SECONDARY outcome

Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=23 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=10 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=20 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Maximum Observed Concentration (Cmax)	449280.231 µg/L Geometric Coefficient of Variation 36.7	452827.419 µg/L Geometric Coefficient of Variation 25.5	482602.748 µg/L Geometric Coefficient of Variation 39.9

SECONDARY outcome

Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1

Time to maximum observed concentration of Durvalumab (DURVA) after multiple doses on day 1 obtained from the observed concentration versus time data

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=23 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=10 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=20 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Time to Maximum Observed Concentration (Tmax)	0.051 day Interval 0.04 to 0.22	0.106 day Interval 0.04 to 0.22	0.180 day Interval 0.04 to 0.22

SECONDARY outcome

Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=23 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=9 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=19 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Terminal Elimination Half-life (t1/2)	10.984 day Geometric Coefficient of Variation 52.1	13.376 day Geometric Coefficient of Variation 90.9	15.844 day Geometric Coefficient of Variation 29.8

SECONDARY outcome

Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1

Outcome measures

Outcome measures
Measure	Cohort A: High Risk, TNE n=23 Participants High risk, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle.	Cohort B: >=65 Years Old, TNE n=9 Participants \>= 65 years old, transplant non-eligible \[TNE\], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance \[CrCl\] value) on Days 1 to 21 of each 28-day treatment cycle • Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (\> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles.	Cohort C: High Risk, Post-transplant n=19 Participants High risk, post-transplant NDMM participants were administered the following as maintenance therapy: • Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle • Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle.
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Clearance (CL)	0.303 L/day Geometric Coefficient of Variation 60.9	0.271 L/day Geometric Coefficient of Variation 62.5	0.230 L/day Geometric Coefficient of Variation 36.4

SECONDARY outcome

Timeframe: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1