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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 LLC (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 Disease Intervention/Treatment Phase
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

Arm Intervention/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 LLC

    Investigators

    • Study Director: Medical Director, Merck Sharp & Dohme LLC

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    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 LLC
    PD1
    PD-1
    PD-L1
    PDL1
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Pembrolizumab
    Lenalidomide

    Study Results

    Participant Flow

    Recruitment Details This study was conducted at 140 centers in 15 countries. The database cutoff date was August 3, 2020.
    Pre-assignment Detail Note: 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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
    STARTED 156 154
    Treated 154 148
    COMPLETED 0 0
    NOT COMPLETED 156 154

    Baseline Characteristics

    Arm/Group Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone Total
    Arm/Group Description 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. 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 Participants 156 154 310
    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
    Title Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 156 154
    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 Hypothesis p-Value 0.33475
    Comments
    Method Log Rank
    Comments One-sided p-value based on Stratified log-rank test.
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.90
    Confidence Interval (2-Sided) 95%
    0.56 to 1.45
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based 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
    Title Overall Survival (OS)
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 156 154
    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 Hypothesis p-Value 0.83416
    Comments
    Method Stratified log-rank test
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.22
    Confidence Interval (2-Sided) 95%
    0.81 to 1.84
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based 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
    Title Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 156 154
    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 Hypothesis p-Value 0.13102
    Comments
    Method One-sided p-value for testing
    Comments H0: difference in % =0 versus H1: difference in % > 0.
    Method of Estimation Estimation Parameter Difference in % vs SOC
    Estimated Value 5.8
    Confidence Interval (2-Sided) 95%
    -4.3 to 15.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Other Statistical Analysis Based 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
    Title Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 116 106
    Median (95% Confidence Interval) [Months]
    NA
    NA
    5. Secondary Outcome
    Title Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 156 154
    Number (95% Confidence Interval) [Percentage of participants]
    89.1
    57.1%
    91.6
    59.5%
    6. Secondary Outcome
    Title Second Progression Free Survival (PFS2)
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 0 0
    7. Secondary Outcome
    Title Number of Participants Who Experienced One or More Adverse Events (AEs)
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 154 148
    Count of Participants [Participants]
    152
    97.4%
    141
    91.6%
    8. Secondary Outcome
    Title Number of Participants Discontinuing Study Treatment Due to an AE
    Description 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.
    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 Participants 154 148
    Count of Participants [Participants]
    44
    28.2%
    26
    16.9%

    Adverse Events

    Time Frame Up 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 Title Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Arm/Group Description 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. 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 + Dexamethasone Lenolidomide + Dexamethasone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 51/156 (32.7%) 43/154 (27.9%)
    Serious Adverse Events
    Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 91/154 (59.1%) 65/148 (43.9%)
    Blood and lymphatic system disorders
    Anaemia 3/154 (1.9%) 3 5/148 (3.4%) 5
    Cytopenia 1/154 (0.6%) 1 0/148 (0%) 0
    Febrile neutropenia 3/154 (1.9%) 3 3/148 (2%) 3
    Neutropenia 2/154 (1.3%) 3 0/148 (0%) 0
    Thrombocytopenia 1/154 (0.6%) 1 0/148 (0%) 0
    Cardiac disorders
    Acute myocardial infarction 0/154 (0%) 0 1/148 (0.7%) 1
    Angina pectoris 1/154 (0.6%) 1 0/148 (0%) 0
    Atrial fibrillation 4/154 (2.6%) 4 2/148 (1.4%) 2
    Atrioventricular block complete 1/154 (0.6%) 1 0/148 (0%) 0
    Bradycardia 1/154 (0.6%) 1 0/148 (0%) 0
    Cardiac arrest 2/154 (1.3%) 2 0/148 (0%) 0
    Cardiac failure 2/154 (1.3%) 2 2/148 (1.4%) 2
    Cardiac failure acute 0/154 (0%) 0 1/148 (0.7%) 1
    Cardiac failure congestive 1/154 (0.6%) 1 1/148 (0.7%) 1
    Cardio-respiratory arrest 2/154 (1.3%) 2 0/148 (0%) 0
    Cardiopulmonary failure 1/154 (0.6%) 1 1/148 (0.7%) 1
    Myocardial infarction 0/154 (0%) 0 2/148 (1.4%) 2
    Myocarditis 2/154 (1.3%) 2 0/148 (0%) 0
    Congenital, familial and genetic disorders
    Fanconi syndrome 1/154 (0.6%) 1 0/148 (0%) 0
    Endocrine disorders
    Adrenal insufficiency 1/154 (0.6%) 1 0/148 (0%) 0
    Hyperthyroidism 4/154 (2.6%) 4 0/148 (0%) 0
    Hypothyroidism 2/154 (1.3%) 2 0/148 (0%) 0
    Inappropriate antidiuretic hormone secretion 1/154 (0.6%) 1 0/148 (0%) 0
    Secondary adrenocortical insufficiency 2/154 (1.3%) 2 0/148 (0%) 0
    Eye disorders
    Cataract 0/154 (0%) 0 1/148 (0.7%) 1
    Gastrointestinal disorders
    Colitis 2/154 (1.3%) 2 0/148 (0%) 0
    Colitis ischaemic 0/154 (0%) 0 1/148 (0.7%) 1
    Constipation 5/154 (3.2%) 6 0/148 (0%) 0
    Diarrhoea 5/154 (3.2%) 5 1/148 (0.7%) 1
    Dysphagia 2/154 (1.3%) 2 0/148 (0%) 0
    Gastrointestinal perforation 0/154 (0%) 0 1/148 (0.7%) 1
    Inguinal hernia strangulated 1/154 (0.6%) 1 0/148 (0%) 0
    Intestinal ischaemia 1/154 (0.6%) 1 0/148 (0%) 0
    Ischaemic enteritis 1/154 (0.6%) 1 0/148 (0%) 0
    Large intestine perforation 1/154 (0.6%) 1 1/148 (0.7%) 1
    Nausea 2/154 (1.3%) 2 0/148 (0%) 0
    Odynophagia 1/154 (0.6%) 1 0/148 (0%) 0
    Pancreatitis 1/154 (0.6%) 1 0/148 (0%) 0
    Pancreatitis acute 0/154 (0%) 0 1/148 (0.7%) 1
    Rectal haemorrhage 1/154 (0.6%) 1 0/148 (0%) 0
    Upper gastrointestinal haemorrhage 0/154 (0%) 0 1/148 (0.7%) 1
    Vomiting 1/154 (0.6%) 1 1/148 (0.7%) 1
    General disorders
    Asthenia 0/154 (0%) 0 1/148 (0.7%) 1
    Chest pain 1/154 (0.6%) 1 3/148 (2%) 3
    Death 0/154 (0%) 0 1/148 (0.7%) 1
    Hypothermia 1/154 (0.6%) 1 0/148 (0%) 0
    Influenza like illness 1/154 (0.6%) 1 0/148 (0%) 0
    Malaise 0/154 (0%) 0 1/148 (0.7%) 1
    Oedema peripheral 1/154 (0.6%) 1 1/148 (0.7%) 1
    Pain 1/154 (0.6%) 1 0/148 (0%) 0
    Pyrexia 8/154 (5.2%) 9 1/148 (0.7%) 1
    Sudden death 1/154 (0.6%) 1 2/148 (1.4%) 2
    Hepatobiliary disorders
    Cholecystitis acute 1/154 (0.6%) 1 0/148 (0%) 0
    Drug-induced liver injury 1/154 (0.6%) 1 0/148 (0%) 0
    Hepatic failure 1/154 (0.6%) 1 0/148 (0%) 0
    Hepatic function abnormal 0/154 (0%) 0 1/148 (0.7%) 1
    Hepatitis 1/154 (0.6%) 1 0/148 (0%) 0
    Infections and infestations
    Abscess jaw 0/154 (0%) 0 1/148 (0.7%) 1
    Arthritis infective 0/154 (0%) 0 1/148 (0.7%) 1
    Bacteraemia 1/154 (0.6%) 2 0/148 (0%) 0
    Bronchitis 2/154 (1.3%) 2 0/148 (0%) 0
    Bronchitis bacterial 1/154 (0.6%) 1 0/148 (0%) 0
    Cellulitis 2/154 (1.3%) 2 1/148 (0.7%) 1
    Clostridium difficile colitis 0/154 (0%) 0 1/148 (0.7%) 1
    Diverticulitis 3/154 (1.9%) 4 0/148 (0%) 0
    Fungaemia 1/154 (0.6%) 1 0/148 (0%) 0
    Gastroenteritis 1/154 (0.6%) 2 0/148 (0%) 0
    Influenza 1/154 (0.6%) 1 0/148 (0%) 0
    Klebsiella sepsis 0/154 (0%) 0 1/148 (0.7%) 1
    Lower respiratory tract infection 3/154 (1.9%) 4 1/148 (0.7%) 1
    Neutropenic sepsis 1/154 (0.6%) 1 0/148 (0%) 0
    Oesophageal candidiasis 0/154 (0%) 0 1/148 (0.7%) 1
    Osteomyelitis 0/154 (0%) 0 1/148 (0.7%) 1
    Peritonitis 0/154 (0%) 0 1/148 (0.7%) 1
    Pneumonia 16/154 (10.4%) 19 10/148 (6.8%) 10
    Pneumonia cytomegaloviral 1/154 (0.6%) 1 0/148 (0%) 0
    Pneumonia pneumococcal 1/154 (0.6%) 1 0/148 (0%) 0
    Pneumonia respiratory syncytial viral 0/154 (0%) 0 1/148 (0.7%) 1
    Pulmonary sepsis 1/154 (0.6%) 1 0/148 (0%) 0
    Pulmonary tuberculosis 1/154 (0.6%) 1 0/148 (0%) 0
    Pyelonephritis 2/154 (1.3%) 2 0/148 (0%) 0
    Respiratory tract infection 1/154 (0.6%) 1 0/148 (0%) 0
    Sepsis 8/154 (5.2%) 8 4/148 (2.7%) 4
    Septic shock 2/154 (1.3%) 2 2/148 (1.4%) 2
    Sinusitis 1/154 (0.6%) 1 0/148 (0%) 0
    Skin infection 1/154 (0.6%) 2 0/148 (0%) 0
    Subcutaneous abscess 1/154 (0.6%) 1 0/148 (0%) 0
    Upper respiratory tract infection 1/154 (0.6%) 1 0/148 (0%) 0
    Urinary tract infection 2/154 (1.3%) 2 2/148 (1.4%) 2
    Urosepsis 1/154 (0.6%) 1 0/148 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose 0/154 (0%) 0 1/148 (0.7%) 1
    Femoral neck fracture 0/154 (0%) 0 2/148 (1.4%) 2
    Femur fracture 0/154 (0%) 0 1/148 (0.7%) 1
    Infusion related reaction 1/154 (0.6%) 1 0/148 (0%) 0
    Pelvic fracture 1/154 (0.6%) 1 0/148 (0%) 0
    Rib fracture 1/154 (0.6%) 1 2/148 (1.4%) 2
    Spinal compression fracture 0/154 (0%) 0 3/148 (2%) 3
    Spinal fracture 1/154 (0.6%) 1 1/148 (0.7%) 1
    Subdural haematoma 1/154 (0.6%) 1 0/148 (0%) 0
    Synovial rupture 1/154 (0.6%) 1 0/148 (0%) 0
    Investigations
    Blood bilirubin increased 1/154 (0.6%) 1 0/148 (0%) 0
    Blood creatinine increased 2/154 (1.3%) 2 0/148 (0%) 0
    Liver function test abnormal 1/154 (0.6%) 1 0/148 (0%) 0
    Neutrophil count decreased 1/154 (0.6%) 1 0/148 (0%) 0
    Transaminases increased 3/154 (1.9%) 3 0/148 (0%) 0
    Troponin increased 1/154 (0.6%) 1 0/148 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 2/154 (1.3%) 2 1/148 (0.7%) 1
    Dehydration 1/154 (0.6%) 1 1/148 (0.7%) 1
    Electrolyte imbalance 0/154 (0%) 0 1/148 (0.7%) 1
    Fulminant type 1 diabetes mellitus 1/154 (0.6%) 1 0/148 (0%) 0
    Hypercalcaemia 0/154 (0%) 0 1/148 (0.7%) 1
    Hyperglycaemia 1/154 (0.6%) 1 1/148 (0.7%) 1
    Hyperkalaemia 1/154 (0.6%) 1 0/148 (0%) 0
    Hypocalcaemia 2/154 (1.3%) 2 1/148 (0.7%) 1
    Hypoglycaemia 1/154 (0.6%) 1 0/148 (0%) 0
    Hypokalaemia 1/154 (0.6%) 1 2/148 (1.4%) 3
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/154 (0.6%) 1 3/148 (2%) 3
    Back pain 3/154 (1.9%) 3 3/148 (2%) 3
    Intervertebral disc protrusion 1/154 (0.6%) 1 0/148 (0%) 0
    Neck pain 1/154 (0.6%) 1 0/148 (0%) 0
    Pain in extremity 1/154 (0.6%) 1 1/148 (0.7%) 1
    Rhabdomyolysis 1/154 (0.6%) 1 0/148 (0%) 0
    Torticollis 0/154 (0%) 0 1/148 (0.7%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Pancreatic carcinoma 1/154 (0.6%) 1 0/148 (0%) 0
    Squamous cell carcinoma 0/154 (0%) 0 1/148 (0.7%) 1
    Tumour pain 1/154 (0.6%) 1 0/148 (0%) 0
    Nervous system disorders
    Aphasia 1/154 (0.6%) 1 0/148 (0%) 0
    Brain injury 1/154 (0.6%) 1 0/148 (0%) 0
    Dizziness 1/154 (0.6%) 1 0/148 (0%) 0
    Encephalopathy 1/154 (0.6%) 1 0/148 (0%) 0
    Epilepsy 1/154 (0.6%) 1 0/148 (0%) 0
    Headache 1/154 (0.6%) 1 0/148 (0%) 0
    Lethargy 1/154 (0.6%) 1 0/148 (0%) 0
    Myasthenia gravis 1/154 (0.6%) 1 0/148 (0%) 0
    Peripheral motor neuropathy 0/154 (0%) 0 1/148 (0.7%) 1
    Presyncope 1/154 (0.6%) 1 1/148 (0.7%) 1
    Syncope 2/154 (1.3%) 2 0/148 (0%) 0
    Transient ischaemic attack 0/154 (0%) 0 1/148 (0.7%) 1
    Dementia Alzheimer's type 0/154 (0%) 0 1/148 (0.7%) 1
    Psychiatric disorders
    Anxiety 1/154 (0.6%) 1 0/148 (0%) 0
    Completed suicide 1/154 (0.6%) 1 0/148 (0%) 0
    Confusional state 0/154 (0%) 0 1/148 (0.7%) 2
    Delirium 1/154 (0.6%) 1 1/148 (0.7%) 1
    Psychotic disorder 1/154 (0.6%) 1 0/148 (0%) 0
    Suicide attempt 1/154 (0.6%) 1 0/148 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 6/154 (3.9%) 6 2/148 (1.4%) 2
    Renal failure 1/154 (0.6%) 1 0/148 (0%) 0
    Renal impairment 2/154 (1.3%) 2 0/148 (0%) 0
    Renal injury 1/154 (0.6%) 1 0/148 (0%) 0
    Urinary retention 2/154 (1.3%) 2 0/148 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory failure 2/154 (1.3%) 2 1/148 (0.7%) 1
    Bronchitis chronic 1/154 (0.6%) 1 0/148 (0%) 0
    Chronic obstructive pulmonary disease 2/154 (1.3%) 2 0/148 (0%) 0
    Cough 0/154 (0%) 0 1/148 (0.7%) 1
    Dyspnoea 3/154 (1.9%) 4 2/148 (1.4%) 2
    Epistaxis 1/154 (0.6%) 1 0/148 (0%) 0
    Hypoxia 0/154 (0%) 0 1/148 (0.7%) 1
    Pneumonia aspiration 0/154 (0%) 0 1/148 (0.7%) 1
    Pneumonitis 1/154 (0.6%) 1 0/148 (0%) 0
    Pulmonary embolism 8/154 (5.2%) 8 0/148 (0%) 0
    Pulmonary oedema 0/154 (0%) 0 1/148 (0.7%) 1
    Respiratory arrest 1/154 (0.6%) 1 0/148 (0%) 0
    Respiratory failure 0/154 (0%) 0 2/148 (1.4%) 2
    Skin and subcutaneous tissue disorders
    Dermatitis exfoliative generalised 2/154 (1.3%) 2 0/148 (0%) 0
    Rash 1/154 (0.6%) 1 0/148 (0%) 0
    Rash erythematous 1/154 (0.6%) 1 0/148 (0%) 0
    Rash maculo-papular 1/154 (0.6%) 1 0/148 (0%) 0
    Skin ulcer 2/154 (1.3%) 2 0/148 (0%) 0
    Stevens-Johnson syndrome 1/154 (0.6%) 1 0/148 (0%) 0
    Vascular disorders
    Aortic aneurysm 0/154 (0%) 0 1/148 (0.7%) 1
    Deep vein thrombosis 2/154 (1.3%) 2 0/148 (0%) 0
    Hypertension 0/154 (0%) 0 1/148 (0.7%) 1
    Hypertensive crisis 0/154 (0%) 0 1/148 (0.7%) 1
    Hypotension 1/154 (0.6%) 1 3/148 (2%) 3
    Orthostatic hypotension 1/154 (0.6%) 1 0/148 (0%) 0
    Venous thrombosis limb 0/154 (0%) 0 1/148 (0.7%) 1
    Other (Not Including Serious) Adverse Events
    Pembrolizumab + Lenalidomide + Dexamethasone Lenolidomide + Dexamethasone
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 143/154 (92.9%) 129/148 (87.2%)
    Blood and lymphatic system disorders
    Anaemia 32/154 (20.8%) 48 27/148 (18.2%) 40
    Neutropenia 30/154 (19.5%) 54 26/148 (17.6%) 51
    Thrombocytopenia 12/154 (7.8%) 16 12/148 (8.1%) 19
    Endocrine disorders
    Hypothyroidism 13/154 (8.4%) 13 1/148 (0.7%) 1
    Eye disorders
    Vision blurred 11/154 (7.1%) 12 3/148 (2%) 3
    Gastrointestinal disorders
    Abdominal pain 13/154 (8.4%) 16 13/148 (8.8%) 18
    Constipation 55/154 (35.7%) 62 33/148 (22.3%) 35
    Diarrhoea 36/154 (23.4%) 51 34/148 (23%) 48
    Dry mouth 12/154 (7.8%) 13 5/148 (3.4%) 5
    Dyspepsia 8/154 (5.2%) 9 2/148 (1.4%) 2
    Nausea 37/154 (24%) 54 33/148 (22.3%) 38
    Stomatitis 9/154 (5.8%) 11 6/148 (4.1%) 6
    Vomiting 30/154 (19.5%) 39 9/148 (6.1%) 16
    General disorders
    Asthenia 11/154 (7.1%) 11 17/148 (11.5%) 20
    Fatigue 44/154 (28.6%) 52 37/148 (25%) 39
    Oedema 8/154 (5.2%) 8 6/148 (4.1%) 7
    Oedema peripheral 25/154 (16.2%) 31 27/148 (18.2%) 28
    Pyrexia 29/154 (18.8%) 41 10/148 (6.8%) 11
    Infections and infestations
    Bronchitis 9/154 (5.8%) 12 4/148 (2.7%) 5
    Nasopharyngitis 11/154 (7.1%) 16 11/148 (7.4%) 13
    Oral candidiasis 15/154 (9.7%) 16 2/148 (1.4%) 2
    Pneumonia 11/154 (7.1%) 11 2/148 (1.4%) 2
    Upper respiratory tract infection 16/154 (10.4%) 16 13/148 (8.8%) 17
    Urinary tract infection 15/154 (9.7%) 16 12/148 (8.1%) 16
    Injury, poisoning and procedural complications
    Contusion 2/154 (1.3%) 3 8/148 (5.4%) 10
    Fall 7/154 (4.5%) 10 9/148 (6.1%) 12
    Investigations
    Alanine aminotransferase increased 11/154 (7.1%) 11 3/148 (2%) 3
    Aspartate aminotransferase increased 8/154 (5.2%) 8 1/148 (0.7%) 1
    Neutrophil count decreased 13/154 (8.4%) 23 12/148 (8.1%) 23
    Weight decreased 10/154 (6.5%) 10 17/148 (11.5%) 18
    Metabolism and nutrition disorders
    Decreased appetite 26/154 (16.9%) 28 19/148 (12.8%) 21
    Dehydration 8/154 (5.2%) 14 5/148 (3.4%) 6
    Gout 8/154 (5.2%) 14 4/148 (2.7%) 5
    Hyperglycaemia 10/154 (6.5%) 17 8/148 (5.4%) 12
    Hypocalcaemia 16/154 (10.4%) 18 8/148 (5.4%) 9
    Hypokalaemia 26/154 (16.9%) 31 17/148 (11.5%) 21
    Hypomagnesaemia 10/154 (6.5%) 10 5/148 (3.4%) 6
    Hyponatraemia 9/154 (5.8%) 10 1/148 (0.7%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 17/154 (11%) 21 9/148 (6.1%) 12
    Back pain 20/154 (13%) 24 17/148 (11.5%) 21
    Muscle spasms 14/154 (9.1%) 17 14/148 (9.5%) 16
    Muscular weakness 11/154 (7.1%) 12 4/148 (2.7%) 5
    Musculoskeletal chest pain 11/154 (7.1%) 11 7/148 (4.7%) 7
    Musculoskeletal pain 11/154 (7.1%) 14 10/148 (6.8%) 11
    Pain in extremity 9/154 (5.8%) 11 8/148 (5.4%) 10
    Nervous system disorders
    Dizziness 14/154 (9.1%) 15 14/148 (9.5%) 15
    Dysgeusia 8/154 (5.2%) 8 12/148 (8.1%) 12
    Headache 9/154 (5.8%) 9 11/148 (7.4%) 14
    Neuropathy peripheral 9/154 (5.8%) 11 12/148 (8.1%) 13
    Tremor 11/154 (7.1%) 11 16/148 (10.8%) 16
    Psychiatric disorders
    Anxiety 12/154 (7.8%) 14 11/148 (7.4%) 12
    Depression 9/154 (5.8%) 10 8/148 (5.4%) 8
    Insomnia 22/154 (14.3%) 25 27/148 (18.2%) 33
    Respiratory, thoracic and mediastinal disorders
    Cough 20/154 (13%) 21 18/148 (12.2%) 19
    Dysphonia 3/154 (1.9%) 6 10/148 (6.8%) 10
    Dyspnoea 19/154 (12.3%) 21 12/148 (8.1%) 12
    Epistaxis 8/154 (5.2%) 8 6/148 (4.1%) 6
    Oropharyngeal pain 8/154 (5.2%) 10 5/148 (3.4%) 5
    Skin and subcutaneous tissue disorders
    Dry skin 9/154 (5.8%) 9 3/148 (2%) 3
    Night sweats 8/154 (5.2%) 10 5/148 (3.4%) 5
    Pruritus 13/154 (8.4%) 17 5/148 (3.4%) 5
    Rash 32/154 (20.8%) 45 19/148 (12.8%) 20
    Rash maculo-papular 14/154 (9.1%) 19 11/148 (7.4%) 13
    Vascular disorders
    Hypotension 12/154 (7.8%) 13 8/148 (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/Title Senior Vice President, Global Clinical Development
    Organization Merck Sharp & Dohme Corp.
    Phone 1-800-672-6372
    Email ClinicalTrialsDisclosure@merck.com
    Responsible Party:
    Merck Sharp & Dohme LLC
    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