Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185)

Sponsor
Merck Sharp & Dohme Corp. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02579863
Collaborator
(none)
310
Enrollment
2
Arms
56.8
Actual Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of lenalidomide and low dose dexamethasone with pembrolizumab (MK-3475) to that of lenalidomide and low dose dexamethasone without pembrolizumab in terms of progression-free survival (PFS) in participants with newly diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell transplant (Auto-SCT). The study's primary hypothesis is that pembrolizumab in dexamethasone prolongs progression free survival (PFS) as assessed by Clinical Adjudication Committee (CAC) blinded central review using International Myeloma Working Group (IMWG) response criteria compared to treatment combination with lenalidomide and low-dose with lenalidomide and low-dose dexamethasone (standard of care, SOC) alone.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
310 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Study of Lenalidomide and Low-Dose Dexamethasone With or Without Pembrolizumab (MK3475) in Newly Diagnosed and Treatment Naïve Multiple Myeloma (KEYNOTE 185).
Actual Study Start Date :
Oct 19, 2015
Actual Primary Completion Date :
Jul 9, 2018
Actual Study Completion Date :
Jul 13, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Pembrolizumab + Lenalidomide + Dexamethasone

Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.

Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • Drug: Lenalidomide
    oral capsules

    Drug: Dexamethasone
    oral tablets

    Active Comparator: Lenalidomide + Dexamethasone

    Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.

    Drug: Lenalidomide
    oral capsules

    Drug: Dexamethasone
    oral tablets

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review [Up to approximately 30 months]

      PFS was defined as the time from randomization to the first documented disease progression (events of new bone lesions, soft tissue plasmacytomas or an increase in existing lesions, or death due to any cause). The median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. Due to the small number of events, the tail of the estimated survival distribution was close to the median for both arms. The higher variability of the tail estimates resulted in observing the median estimate in the experimental arm but not in the standard of care arm even when number of events in 2 arms were similar. The database cutoff date was July 9, 2018.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Up to approximately 55 months]

      OS was defined as the time from randomization to death due to any cause. OS was calculated from the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. This is an event-driven (events of death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). The database cutoff date was August 3, 2020.

    2. Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review [Up to approximately 30 months]

      ORR was based on participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]) according to the IMWG. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018.

    3. Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review [Up to approximately 30 months]

      Response duration was defined as the time from first documented evidence of at least a partial response (sCR+CR+VGPR+PR]), until confirmed disease progression or death. DOR was calculated from product-limit (Kaplan-Meier) method for censored data. This is an event-driven (events of disease progression and death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). Full Range is the minimum and maximum of the observed duration of response. The data cutoff date was July 9, 2018.

    4. Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review [Up to approximately 30 months]

      Disease control rate was defined as the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, or have demonstrated SD for at least 12 weeks prior to any evidence of progression. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours; SD = not meeting the criteria for CR, VGPR, PR, or PD; PD = development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Data cutoff date was July 9, 2018.

    5. Second Progression Free Survival (PFS2) [Up to approximately 55 months]

      PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. PFS was assessed by Clinical Adjudication Committee (CAC) blinded central review according to the IMWG response criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. PFS2 was not completed due to incomplete enrollment for a clinical hold and study cancellation.

    6. Number of Participants Who Experienced One or More Adverse Events (AEs) [Up to approximately 55 months]

      An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020.

    7. Number of Participants Discontinuing Study Treatment Due to an AE [Up to approximately 55 months]

      An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Confirmed diagnosis of active multiple myeloma and measurable disease.

    • Ineligible to receive treatment with auto-SCT due to age (≥65 years old) or any significant coexisting medical condition (cardiac, renal, pulmonary or hepatic dysfunction), likely to have a negative impact on tolerability of auto-SCT. Participants <65 years of age who refuse auto-SCT are not eligible for this study.

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

    • Female participants of childbearing potential must have 2 negative urine pregnancy tests (with a sensitivity of at least 25 Milli-international units/milliliter) within 10 to 14 days and within 24 hours prior to receiving study medication.

    • Female participants of childbearing potential must agree to use adequate contraception 28 days prior to study start, continuing throughout the study, and for up to 28 days after the last dose of lenalidomide (or 120 days after the last dose of pembrolizumab).

    • Male participants of childbearing potential must agree to use adequate contraception from the first dose of study medication, continuing throughout the study, and for up to 28 days after the last dose of lenalidomide (or 120 days after the last dose of pembrolizumab).

    Exclusion Criteria:
    • Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years.

    • Has peripheral neuropathy ≥ Grade 2.

    • Has a known additional malignancy that is progressing or requires active treatment within the last 5 years (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).

    • Has history of non-infectious pneumonitis that required steroids or current pneumonitis

    • Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).

    • Has a known Human Immunodeficiency Virus (HIV), or a known, active Hepatitis B (HBV), or a known, active Hepatitis C (HCV) infection.

    • Is unable or unwilling to undergo thromboembolic prophylaxis including, as clinically indicated, aspirin, Coumadin (warfarin) or low-molecular weight heparin.

    • Has lactose intolerance.

    • Has an invasive fungal infection.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Merck Sharp & Dohme Corp.

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme Corp.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme Corp.
    ClinicalTrials.gov Identifier:
    NCT02579863
    Other Study ID Numbers:
    • 3475-185
    • 2015-002901-12
    • 163239
    • MK-3475-185
    • KEYNOTE-185
    First Posted:
    Oct 20, 2015
    Last Update Posted:
    Jul 20, 2021
    Last Verified:
    Jun 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Merck Sharp & Dohme Corp.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsThis study was conducted at 140 centers in 15 countries. The database cutoff date was August 3, 2020.
    Pre-assignment DetailNote: Due to administrative reasons (a noncompliant site), 2 participants in the Pembrolizumab plus SOC arm and one participant in the SOC arm, were recorded as "Ongoing in Trial" in the CSR Disposition Table and "Final Disposition Unknown" here.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Period Title: Overall Study
    STARTED156154
    Treated154148
    COMPLETED00
    NOT COMPLETED156154

    Baseline Characteristics

    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + DexamethasoneTotal
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Total of all reporting groups
    Overall Participants156154310
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    74.4
    (6.0)
    74.3
    (5.9)
    74.3
    (6.0)
    Sex: Female, Male (Count of Participants)
    Female
    85
    54.5%
    81
    52.6%
    166
    53.5%
    Male
    71
    45.5%
    73
    47.4%
    144
    46.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    4
    2.6%
    4
    2.6%
    8
    2.6%
    Not Hispanic or Latino
    143
    91.7%
    136
    88.3%
    279
    90%
    Unknown or Not Reported
    9
    5.8%
    14
    9.1%
    23
    7.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    27
    17.3%
    27
    17.5%
    54
    17.4%
    Native Hawaiian or Other Pacific Islander
    1
    0.6%
    0
    0%
    1
    0.3%
    Black or African American
    9
    5.8%
    3
    1.9%
    12
    3.9%
    White
    115
    73.7%
    121
    78.6%
    236
    76.1%
    More than one race
    1
    0.6%
    0
    0%
    1
    0.3%
    Unknown or Not Reported
    3
    1.9%
    3
    1.9%
    6
    1.9%
    International Stage (I, II, III). (Number) [Number]
    Stage I
    39
    25%
    53
    34.4%
    92
    29.7%
    Stage II
    70
    44.9%
    66
    42.9%
    136
    43.9%
    Stage III
    46
    29.5%
    34
    22.1%
    80
    25.8%
    Missing
    1
    0.6%
    1
    0.6%
    2
    0.6%

    Outcome Measures

    1. Primary Outcome
    TitleProgression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review
    DescriptionPFS was defined as the time from randomization to the first documented disease progression (events of new bone lesions, soft tissue plasmacytomas or an increase in existing lesions, or death due to any cause). The median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. Due to the small number of events, the tail of the estimated survival distribution was close to the median for both arms. The higher variability of the tail estimates resulted in observing the median estimate in the experimental arm but not in the standard of care arm even when number of events in 2 arms were similar. The database cutoff date was July 9, 2018.
    Time FrameUp to approximately 30 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants156154
    Median (95% Confidence Interval) [Months]
    19.6
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Lenalidomide + Dexamethasone, Lenolidomide + Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.33475
    Comments
    MethodLog Rank
    CommentsOne-sided p-value based on Stratified log-rank test.
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value0.90
    Confidence Interval (2-Sided) 95%
    0.56 to 1.45
    Parameter Dispersion Type:
    Value:
    Estimation CommentsBased on Cox regression model with treatment as a covariate stratified by Age (<75 years vs >= 75 years) and ISS stage (I or II vs. III).
    2. Secondary Outcome
    TitleOverall Survival (OS)
    DescriptionOS was defined as the time from randomization to death due to any cause. OS was calculated from the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. This is an event-driven (events of death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). The database cutoff date was August 3, 2020.
    Time FrameUp to approximately 55 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants156154
    Median (95% Confidence Interval) [Months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Lenalidomide + Dexamethasone, Lenolidomide + Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.83416
    Comments
    MethodStratified log-rank test
    Comments
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.22
    Confidence Interval (2-Sided) 95%
    0.81 to 1.84
    Parameter Dispersion Type:
    Value:
    Estimation CommentsBased on Cox regression model with treatment as a covariate stratified by "Age" (<75 years vs >= 75 years) and "ISS stage" (I or II vs. III).
    3. Secondary Outcome
    TitleOverall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
    DescriptionORR was based on participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]) according to the IMWG. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018.
    Time FrameUp to approximately 30 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants156154
    Number (95% Confidence Interval) [Percentage of participants]
    74.4
    47.7%
    68.8
    44.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab + Lenalidomide + Dexamethasone, Lenolidomide + Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.13102
    Comments
    MethodOne-sided p-value for testing
    CommentsH0: difference in % =0 versus H1: difference in % > 0.
    Method of EstimationEstimation ParameterDifference in % vs SOC
    Estimated Value5.8
    Confidence Interval (2-Sided) 95%
    -4.3 to 15.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Other Statistical AnalysisBased on Miettinen & Nurminen method stratified by 'Age' (<75 years vs >= 75 years) and 'ISS stage' (I or II vs. III); If there were no participants in one of the treatment groups involved in a comparison for a particular stratum, then that stratum was excluded from the treatment comparison.
    4. Secondary Outcome
    TitleDuration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review
    DescriptionResponse duration was defined as the time from first documented evidence of at least a partial response (sCR+CR+VGPR+PR]), until confirmed disease progression or death. DOR was calculated from product-limit (Kaplan-Meier) method for censored data. This is an event-driven (events of disease progression and death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). Full Range is the minimum and maximum of the observed duration of response. The data cutoff date was July 9, 2018.
    Time FrameUp to approximately 30 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all randomized participants who demonstrated at least a partial response. Participants were included in the treatment group to which they were randomized.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants116106
    Median (95% Confidence Interval) [Months]
    NA
    NA
    5. Secondary Outcome
    TitleDisease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
    DescriptionDisease control rate was defined as the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, or have demonstrated SD for at least 12 weeks prior to any evidence of progression. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours; SD = not meeting the criteria for CR, VGPR, PR, or PD; PD = development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Data cutoff date was July 9, 2018.
    Time FrameUp to approximately 30 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants156154
    Number (95% Confidence Interval) [Percentage of participants]
    89.1
    57.1%
    91.6
    59.5%
    6. Secondary Outcome
    TitleSecond Progression Free Survival (PFS2)
    DescriptionPFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. PFS was assessed by Clinical Adjudication Committee (CAC) blinded central review according to the IMWG response criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. PFS2 was not completed due to incomplete enrollment for a clinical hold and study cancellation.
    Time FrameUp to approximately 55 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized. PFS2 was not completed due to incomplete enrollment for a clinical hold and study cancellation.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants00
    7. Secondary Outcome
    TitleNumber of Participants Who Experienced One or More Adverse Events (AEs)
    DescriptionAn AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020.
    Time FrameUp to approximately 55 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all randomized participants who received at least one dose of study treatment.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants154148
    Count of Participants [Participants]
    152
    97.4%
    141
    91.6%
    8. Secondary Outcome
    TitleNumber of Participants Discontinuing Study Treatment Due to an AE
    DescriptionAn AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020.
    Time FrameUp to approximately 55 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all randomized participants who received at least one dose of study treatment.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    Measure Participants154148
    Count of Participants [Participants]
    44
    28.2%
    26
    16.9%

    Adverse Events

    Time FrameUp to approximately 55 months
    Adverse Event Reporting Description The All-Cause Mortality analysis used all randomized participants whereas adverse events were collected for all treated participants. Disease progression of cancer under study was not considered an adverse event (AE) unless related to study treatment. Medical Dictionary for Regulatory Activities (MedDRA) preferred terms Neoplasm progression, Malignant neoplasm progression and Disease progression not related to study treatment were excluded as AEs. The Database Cutoff Date was Aug. 3, 2020.
    Arm/Group TitlePembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Arm/Group DescriptionParticipants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
    All Cause Mortality
    Pembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total51/156 (32.7%) 43/154 (27.9%)
    Serious Adverse Events
    Pembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total91/154 (59.1%) 65/148 (43.9%)
    Blood and lymphatic system disorders
    Anaemia3/154 (1.9%) 35/148 (3.4%) 5
    Cytopenia1/154 (0.6%) 10/148 (0%) 0
    Febrile neutropenia3/154 (1.9%) 33/148 (2%) 3
    Neutropenia2/154 (1.3%) 30/148 (0%) 0
    Thrombocytopenia1/154 (0.6%) 10/148 (0%) 0
    Cardiac disorders
    Acute myocardial infarction0/154 (0%) 01/148 (0.7%) 1
    Angina pectoris1/154 (0.6%) 10/148 (0%) 0
    Atrial fibrillation4/154 (2.6%) 42/148 (1.4%) 2
    Atrioventricular block complete1/154 (0.6%) 10/148 (0%) 0
    Bradycardia1/154 (0.6%) 10/148 (0%) 0
    Cardiac arrest2/154 (1.3%) 20/148 (0%) 0
    Cardiac failure2/154 (1.3%) 22/148 (1.4%) 2
    Cardiac failure acute0/154 (0%) 01/148 (0.7%) 1
    Cardiac failure congestive1/154 (0.6%) 11/148 (0.7%) 1
    Cardio-respiratory arrest2/154 (1.3%) 20/148 (0%) 0
    Cardiopulmonary failure1/154 (0.6%) 11/148 (0.7%) 1
    Myocardial infarction0/154 (0%) 02/148 (1.4%) 2
    Myocarditis2/154 (1.3%) 20/148 (0%) 0
    Congenital, familial and genetic disorders
    Fanconi syndrome1/154 (0.6%) 10/148 (0%) 0
    Endocrine disorders
    Adrenal insufficiency1/154 (0.6%) 10/148 (0%) 0
    Hyperthyroidism4/154 (2.6%) 40/148 (0%) 0
    Hypothyroidism2/154 (1.3%) 20/148 (0%) 0
    Inappropriate antidiuretic hormone secretion1/154 (0.6%) 10/148 (0%) 0
    Secondary adrenocortical insufficiency2/154 (1.3%) 20/148 (0%) 0
    Eye disorders
    Cataract0/154 (0%) 01/148 (0.7%) 1
    Gastrointestinal disorders
    Colitis2/154 (1.3%) 20/148 (0%) 0
    Colitis ischaemic0/154 (0%) 01/148 (0.7%) 1
    Constipation5/154 (3.2%) 60/148 (0%) 0
    Diarrhoea5/154 (3.2%) 51/148 (0.7%) 1
    Dysphagia2/154 (1.3%) 20/148 (0%) 0
    Gastrointestinal perforation0/154 (0%) 01/148 (0.7%) 1
    Inguinal hernia strangulated1/154 (0.6%) 10/148 (0%) 0
    Intestinal ischaemia1/154 (0.6%) 10/148 (0%) 0
    Ischaemic enteritis1/154 (0.6%) 10/148 (0%) 0
    Large intestine perforation1/154 (0.6%) 11/148 (0.7%) 1
    Nausea2/154 (1.3%) 20/148 (0%) 0
    Odynophagia1/154 (0.6%) 10/148 (0%) 0
    Pancreatitis1/154 (0.6%) 10/148 (0%) 0
    Pancreatitis acute0/154 (0%) 01/148 (0.7%) 1
    Rectal haemorrhage1/154 (0.6%) 10/148 (0%) 0
    Upper gastrointestinal haemorrhage0/154 (0%) 01/148 (0.7%) 1
    Vomiting1/154 (0.6%) 11/148 (0.7%) 1
    General disorders
    Asthenia0/154 (0%) 01/148 (0.7%) 1
    Chest pain1/154 (0.6%) 13/148 (2%) 3
    Death0/154 (0%) 01/148 (0.7%) 1
    Hypothermia1/154 (0.6%) 10/148 (0%) 0
    Influenza like illness1/154 (0.6%) 10/148 (0%) 0
    Malaise0/154 (0%) 01/148 (0.7%) 1
    Oedema peripheral1/154 (0.6%) 11/148 (0.7%) 1
    Pain1/154 (0.6%) 10/148 (0%) 0
    Pyrexia8/154 (5.2%) 91/148 (0.7%) 1
    Sudden death1/154 (0.6%) 12/148 (1.4%) 2
    Hepatobiliary disorders
    Cholecystitis acute1/154 (0.6%) 10/148 (0%) 0
    Drug-induced liver injury1/154 (0.6%) 10/148 (0%) 0
    Hepatic failure1/154 (0.6%) 10/148 (0%) 0
    Hepatic function abnormal0/154 (0%) 01/148 (0.7%) 1
    Hepatitis1/154 (0.6%) 10/148 (0%) 0
    Infections and infestations
    Abscess jaw0/154 (0%) 01/148 (0.7%) 1
    Arthritis infective0/154 (0%) 01/148 (0.7%) 1
    Bacteraemia1/154 (0.6%) 20/148 (0%) 0
    Bronchitis2/154 (1.3%) 20/148 (0%) 0
    Bronchitis bacterial1/154 (0.6%) 10/148 (0%) 0
    Cellulitis2/154 (1.3%) 21/148 (0.7%) 1
    Clostridium difficile colitis0/154 (0%) 01/148 (0.7%) 1
    Diverticulitis3/154 (1.9%) 40/148 (0%) 0
    Fungaemia1/154 (0.6%) 10/148 (0%) 0
    Gastroenteritis1/154 (0.6%) 20/148 (0%) 0
    Influenza1/154 (0.6%) 10/148 (0%) 0
    Klebsiella sepsis0/154 (0%) 01/148 (0.7%) 1
    Lower respiratory tract infection3/154 (1.9%) 41/148 (0.7%) 1
    Neutropenic sepsis1/154 (0.6%) 10/148 (0%) 0
    Oesophageal candidiasis0/154 (0%) 01/148 (0.7%) 1
    Osteomyelitis0/154 (0%) 01/148 (0.7%) 1
    Peritonitis0/154 (0%) 01/148 (0.7%) 1
    Pneumonia16/154 (10.4%) 1910/148 (6.8%) 10
    Pneumonia cytomegaloviral1/154 (0.6%) 10/148 (0%) 0
    Pneumonia pneumococcal1/154 (0.6%) 10/148 (0%) 0
    Pneumonia respiratory syncytial viral0/154 (0%) 01/148 (0.7%) 1
    Pulmonary sepsis1/154 (0.6%) 10/148 (0%) 0
    Pulmonary tuberculosis1/154 (0.6%) 10/148 (0%) 0
    Pyelonephritis2/154 (1.3%) 20/148 (0%) 0
    Respiratory tract infection1/154 (0.6%) 10/148 (0%) 0
    Sepsis8/154 (5.2%) 84/148 (2.7%) 4
    Septic shock2/154 (1.3%) 22/148 (1.4%) 2
    Sinusitis1/154 (0.6%) 10/148 (0%) 0
    Skin infection1/154 (0.6%) 20/148 (0%) 0
    Subcutaneous abscess1/154 (0.6%) 10/148 (0%) 0
    Upper respiratory tract infection1/154 (0.6%) 10/148 (0%) 0
    Urinary tract infection2/154 (1.3%) 22/148 (1.4%) 2
    Urosepsis1/154 (0.6%) 10/148 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose0/154 (0%) 01/148 (0.7%) 1
    Femoral neck fracture0/154 (0%) 02/148 (1.4%) 2
    Femur fracture0/154 (0%) 01/148 (0.7%) 1
    Infusion related reaction1/154 (0.6%) 10/148 (0%) 0
    Pelvic fracture1/154 (0.6%) 10/148 (0%) 0
    Rib fracture1/154 (0.6%) 12/148 (1.4%) 2
    Spinal compression fracture0/154 (0%) 03/148 (2%) 3
    Spinal fracture1/154 (0.6%) 11/148 (0.7%) 1
    Subdural haematoma1/154 (0.6%) 10/148 (0%) 0
    Synovial rupture1/154 (0.6%) 10/148 (0%) 0
    Investigations
    Blood bilirubin increased1/154 (0.6%) 10/148 (0%) 0
    Blood creatinine increased2/154 (1.3%) 20/148 (0%) 0
    Liver function test abnormal1/154 (0.6%) 10/148 (0%) 0
    Neutrophil count decreased1/154 (0.6%) 10/148 (0%) 0
    Transaminases increased3/154 (1.9%) 30/148 (0%) 0
    Troponin increased1/154 (0.6%) 10/148 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite2/154 (1.3%) 21/148 (0.7%) 1
    Dehydration1/154 (0.6%) 11/148 (0.7%) 1
    Electrolyte imbalance0/154 (0%) 01/148 (0.7%) 1
    Fulminant type 1 diabetes mellitus1/154 (0.6%) 10/148 (0%) 0
    Hypercalcaemia0/154 (0%) 01/148 (0.7%) 1
    Hyperglycaemia1/154 (0.6%) 11/148 (0.7%) 1
    Hyperkalaemia1/154 (0.6%) 10/148 (0%) 0
    Hypocalcaemia2/154 (1.3%) 21/148 (0.7%) 1
    Hypoglycaemia1/154 (0.6%) 10/148 (0%) 0
    Hypokalaemia1/154 (0.6%) 12/148 (1.4%) 3
    Musculoskeletal and connective tissue disorders
    Arthralgia1/154 (0.6%) 13/148 (2%) 3
    Back pain3/154 (1.9%) 33/148 (2%) 3
    Intervertebral disc protrusion1/154 (0.6%) 10/148 (0%) 0
    Neck pain1/154 (0.6%) 10/148 (0%) 0
    Pain in extremity1/154 (0.6%) 11/148 (0.7%) 1
    Rhabdomyolysis1/154 (0.6%) 10/148 (0%) 0
    Torticollis0/154 (0%) 01/148 (0.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pancreatic carcinoma1/154 (0.6%) 10/148 (0%) 0
    Squamous cell carcinoma0/154 (0%) 01/148 (0.7%) 1
    Tumour pain1/154 (0.6%) 10/148 (0%) 0
    Nervous system disorders
    Aphasia1/154 (0.6%) 10/148 (0%) 0
    Brain injury1/154 (0.6%) 10/148 (0%) 0
    Dizziness1/154 (0.6%) 10/148 (0%) 0
    Encephalopathy1/154 (0.6%) 10/148 (0%) 0
    Epilepsy1/154 (0.6%) 10/148 (0%) 0
    Headache1/154 (0.6%) 10/148 (0%) 0
    Lethargy1/154 (0.6%) 10/148 (0%) 0
    Myasthenia gravis1/154 (0.6%) 10/148 (0%) 0
    Peripheral motor neuropathy0/154 (0%) 01/148 (0.7%) 1
    Presyncope1/154 (0.6%) 11/148 (0.7%) 1
    Syncope2/154 (1.3%) 20/148 (0%) 0
    Transient ischaemic attack0/154 (0%) 01/148 (0.7%) 1
    Dementia Alzheimer's type0/154 (0%) 01/148 (0.7%) 1
    Psychiatric disorders
    Anxiety1/154 (0.6%) 10/148 (0%) 0
    Completed suicide1/154 (0.6%) 10/148 (0%) 0
    Confusional state0/154 (0%) 01/148 (0.7%) 2
    Delirium1/154 (0.6%) 11/148 (0.7%) 1
    Psychotic disorder1/154 (0.6%) 10/148 (0%) 0
    Suicide attempt1/154 (0.6%) 10/148 (0%) 0
    Renal and urinary disorders
    Acute kidney injury6/154 (3.9%) 62/148 (1.4%) 2
    Renal failure1/154 (0.6%) 10/148 (0%) 0
    Renal impairment2/154 (1.3%) 20/148 (0%) 0
    Renal injury1/154 (0.6%) 10/148 (0%) 0
    Urinary retention2/154 (1.3%) 20/148 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure2/154 (1.3%) 21/148 (0.7%) 1
    Bronchitis chronic1/154 (0.6%) 10/148 (0%) 0
    Chronic obstructive pulmonary disease2/154 (1.3%) 20/148 (0%) 0
    Cough0/154 (0%) 01/148 (0.7%) 1
    Dyspnoea3/154 (1.9%) 42/148 (1.4%) 2
    Epistaxis1/154 (0.6%) 10/148 (0%) 0
    Hypoxia0/154 (0%) 01/148 (0.7%) 1
    Pneumonia aspiration0/154 (0%) 01/148 (0.7%) 1
    Pneumonitis1/154 (0.6%) 10/148 (0%) 0
    Pulmonary embolism8/154 (5.2%) 80/148 (0%) 0
    Pulmonary oedema0/154 (0%) 01/148 (0.7%) 1
    Respiratory arrest1/154 (0.6%) 10/148 (0%) 0
    Respiratory failure0/154 (0%) 02/148 (1.4%) 2
    Skin and subcutaneous tissue disorders
    Dermatitis exfoliative generalised2/154 (1.3%) 20/148 (0%) 0
    Rash1/154 (0.6%) 10/148 (0%) 0
    Rash erythematous1/154 (0.6%) 10/148 (0%) 0
    Rash maculo-papular1/154 (0.6%) 10/148 (0%) 0
    Skin ulcer2/154 (1.3%) 20/148 (0%) 0
    Stevens-Johnson syndrome1/154 (0.6%) 10/148 (0%) 0
    Vascular disorders
    Aortic aneurysm0/154 (0%) 01/148 (0.7%) 1
    Deep vein thrombosis2/154 (1.3%) 20/148 (0%) 0
    Hypertension0/154 (0%) 01/148 (0.7%) 1
    Hypertensive crisis0/154 (0%) 01/148 (0.7%) 1
    Hypotension1/154 (0.6%) 13/148 (2%) 3
    Orthostatic hypotension1/154 (0.6%) 10/148 (0%) 0
    Venous thrombosis limb0/154 (0%) 01/148 (0.7%) 1
    Other (Not Including Serious) Adverse Events
    Pembrolizumab + Lenalidomide + DexamethasoneLenolidomide + Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total143/154 (92.9%) 129/148 (87.2%)
    Blood and lymphatic system disorders
    Anaemia32/154 (20.8%) 4827/148 (18.2%) 40
    Neutropenia30/154 (19.5%) 5426/148 (17.6%) 51
    Thrombocytopenia12/154 (7.8%) 1612/148 (8.1%) 19
    Endocrine disorders
    Hypothyroidism13/154 (8.4%) 131/148 (0.7%) 1
    Eye disorders
    Vision blurred11/154 (7.1%) 123/148 (2%) 3
    Gastrointestinal disorders
    Abdominal pain13/154 (8.4%) 1613/148 (8.8%) 18
    Constipation55/154 (35.7%) 6233/148 (22.3%) 35
    Diarrhoea36/154 (23.4%) 5134/148 (23%) 48
    Dry mouth12/154 (7.8%) 135/148 (3.4%) 5
    Dyspepsia8/154 (5.2%) 92/148 (1.4%) 2
    Nausea37/154 (24%) 5433/148 (22.3%) 38
    Stomatitis9/154 (5.8%) 116/148 (4.1%) 6
    Vomiting30/154 (19.5%) 399/148 (6.1%) 16
    General disorders
    Asthenia11/154 (7.1%) 1117/148 (11.5%) 20
    Fatigue44/154 (28.6%) 5237/148 (25%) 39
    Oedema8/154 (5.2%) 86/148 (4.1%) 7
    Oedema peripheral25/154 (16.2%) 3127/148 (18.2%) 28
    Pyrexia29/154 (18.8%) 4110/148 (6.8%) 11
    Infections and infestations
    Bronchitis9/154 (5.8%) 124/148 (2.7%) 5
    Nasopharyngitis11/154 (7.1%) 1611/148 (7.4%) 13
    Oral candidiasis15/154 (9.7%) 162/148 (1.4%) 2
    Pneumonia11/154 (7.1%) 112/148 (1.4%) 2
    Upper respiratory tract infection16/154 (10.4%) 1613/148 (8.8%) 17
    Urinary tract infection15/154 (9.7%) 1612/148 (8.1%) 16
    Injury, poisoning and procedural complications
    Contusion2/154 (1.3%) 38/148 (5.4%) 10
    Fall7/154 (4.5%) 109/148 (6.1%) 12
    Investigations
    Alanine aminotransferase increased11/154 (7.1%) 113/148 (2%) 3
    Aspartate aminotransferase increased8/154 (5.2%) 81/148 (0.7%) 1
    Neutrophil count decreased13/154 (8.4%) 2312/148 (8.1%) 23
    Weight decreased10/154 (6.5%) 1017/148 (11.5%) 18
    Metabolism and nutrition disorders
    Decreased appetite26/154 (16.9%) 2819/148 (12.8%) 21
    Dehydration8/154 (5.2%) 145/148 (3.4%) 6
    Gout8/154 (5.2%) 144/148 (2.7%) 5
    Hyperglycaemia10/154 (6.5%) 178/148 (5.4%) 12
    Hypocalcaemia16/154 (10.4%) 188/148 (5.4%) 9
    Hypokalaemia26/154 (16.9%) 3117/148 (11.5%) 21
    Hypomagnesaemia10/154 (6.5%) 105/148 (3.4%) 6
    Hyponatraemia9/154 (5.8%) 101/148 (0.7%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia17/154 (11%) 219/148 (6.1%) 12
    Back pain20/154 (13%) 2417/148 (11.5%) 21
    Muscle spasms14/154 (9.1%) 1714/148 (9.5%) 16
    Muscular weakness11/154 (7.1%) 124/148 (2.7%) 5
    Musculoskeletal chest pain11/154 (7.1%) 117/148 (4.7%) 7
    Musculoskeletal pain11/154 (7.1%) 1410/148 (6.8%) 11
    Pain in extremity9/154 (5.8%) 118/148 (5.4%) 10
    Nervous system disorders
    Dizziness14/154 (9.1%) 1514/148 (9.5%) 15
    Dysgeusia8/154 (5.2%) 812/148 (8.1%) 12
    Headache9/154 (5.8%) 911/148 (7.4%) 14
    Neuropathy peripheral9/154 (5.8%) 1112/148 (8.1%) 13
    Tremor11/154 (7.1%) 1116/148 (10.8%) 16
    Psychiatric disorders
    Anxiety12/154 (7.8%) 1411/148 (7.4%) 12
    Depression9/154 (5.8%) 108/148 (5.4%) 8
    Insomnia22/154 (14.3%) 2527/148 (18.2%) 33
    Respiratory, thoracic and mediastinal disorders
    Cough20/154 (13%) 2118/148 (12.2%) 19
    Dysphonia3/154 (1.9%) 610/148 (6.8%) 10
    Dyspnoea19/154 (12.3%) 2112/148 (8.1%) 12
    Epistaxis8/154 (5.2%) 86/148 (4.1%) 6
    Oropharyngeal pain8/154 (5.2%) 105/148 (3.4%) 5
    Skin and subcutaneous tissue disorders
    Dry skin9/154 (5.8%) 93/148 (2%) 3
    Night sweats8/154 (5.2%) 105/148 (3.4%) 5
    Pruritus13/154 (8.4%) 175/148 (3.4%) 5
    Rash32/154 (20.8%) 4519/148 (12.8%) 20
    Rash maculo-papular14/154 (9.1%) 1911/148 (7.4%) 13
    Vascular disorders
    Hypotension12/154 (7.8%) 138/148 (5.4%) 9

    Limitations/Caveats

    The MK-3475-185 study was stopped/terminated early. Endpoint statistics may be biased due to the incomplete treatment and follow-up of participants after study termination

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

    Results Point of Contact

    Name/TitleSenior Vice President, Global Clinical Development
    OrganizationMerck Sharp & Dohme Corp.
    Phone1-800-672-6372
    EmailClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme Corp.
    ClinicalTrials.gov Identifier:
    NCT02579863
    Other Study ID Numbers:
    • 3475-185
    • 2015-002901-12
    • 163239
    • MK-3475-185
    • KEYNOTE-185
    First Posted:
    Oct 20, 2015
    Last Update Posted:
    Jul 20, 2021
    Last Verified:
    Jun 1, 2021