Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (MK-3475-183/KEYNOTE-183)

Sponsor
Merck Sharp & Dohme Corp. (Industry)
Overall Status
Terminated
CT.gov ID
NCT02576977
Collaborator
(none)
251
Enrollment
2
Arms
56.9
Actual Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of pomalidomide and low dose dexamethasone with pembrolizumab (MK-3475) to that of pomalidomide and low dose dexamethasone without pembrolizumab in terms of Progression-Free Survival (PFS) in participants with refractory or relapsed and refractory multiple myeloma (rrMM) who have undergone at least 2 lines of prior treatment. The study's 2 primary hypotheses are: 1. Pembrolizumab in combination with pomalidomide and low dose dexamethasone prolongs PFS as assessed by Clinical Adjudication Committee (CAC) blinded central review using International Myeloma Working Group Criteria for Response Assessment in Multiple Myeloma (IMWG) criteria compared to treatment with pomalidomide and low dose dexamethasone standard of care (SOC) alone. 2. Pembrolizumab in combination with pomalidomide and low dose dexamethasone prolongs OS compared to treatment with pomalidomide and low dose dexamethasone (SOC) alone.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
251 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase III Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (KEYNOTE 183)
Actual Study Start Date :
Oct 19, 2015
Actual Primary Completion Date :
Jul 9, 2018
Actual Study Completion Date :
Jul 16, 2020

Arms and Interventions

ArmIntervention/Treatment
Experimental: Pembrolizumab+Pomalidomide+Dexamethasone

Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.

Biological: Pembrolizumab
pembrolizumab 200 mg IV infusion
Other Names:
  • KEYTRUDA®
  • MK-3475
  • SCH 9000475
  • Drug: Pomalidomide
    pomalidomide 4 mg capsules
    Other Names:
  • POMALYST®
  • Drug: Dexamethasone
    dexamethasone 40 mg tablets

    Active Comparator: Pomalidomide+Dexamethasone

    Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.

    Drug: Pomalidomide
    pomalidomide 4 mg capsules
    Other Names:
  • POMALYST®
  • Drug: Dexamethasone
    dexamethasone 40 mg tablets

    Outcome Measures

    Primary Outcome Measures

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

      Progression free survival was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS was assessed by CAC blinded central review according to the IMWG 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. Median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was July 9, 2018.

    2. Overall Survival (OS) [Up to approximately 54 months]

      Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Median overall survival was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was August 3, 2020.

    Secondary Outcome Measures

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

      ORR was defined as the percentage of the participants in the analysis population 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 database cutoff date was July 9, 2018.

    2. Participants Experiencing One or More Adverse Events (AEs) [Up to approximately 54 months]

      An adverse event (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. Database cutoff was August 3, 2020.

    3. Participants Discontinuing Study Investigational Product Due to an AE [Up to approximately 54 months]

      An adverse event 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. Database cutoff was August 3, 2020.

    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 the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, minimal response (MR) or have demonstrated stable disease (SD) for at least 12 weeks prior to any evidence of progression. PD was development of or an increase in the size of bone lesions or soft tissue plasmacytomas. 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 FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry/fluorescence; 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.

    5. Second Progression Free Survival (PFS2) [Up to approximately 30 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. As a result of a full clinical hold by FDA that led to discontinuation of study enrollment, no data was collected for analysis of PFS2.

    Eligibility Criteria

    Criteria

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

    • Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and must have failed last line of treatment (refractory to last line of treatment)

    • Prior anti-myeloma treatments must have included an immunomodulatory drug (IMiD) AND proteasome inhibitor alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor

    • Has performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale

    • Female participants of childbearing potential must have 2 negative urine human chorionic gonadotropin tests within 10 to 14 days and within 24 hours prior to receiving study medication

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

    Exclusion Criteria:
    • Has had prior anti-myeloma therapy within 2 weeks prior to study start and has not recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events due to a previously administered agent

    • Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease [GVHD]).

    • Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first infusion or is planning for or is eligible for auto-SCT

    • Has received previous therapy with pomalidomide

    • 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 a 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), antiprogrammed 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 costimulation or checkpoint pathways)

    • Is pregnant or breast-feeding

    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

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme Corp.
    ClinicalTrials.gov Identifier:
    NCT02576977
    Other Study ID Numbers:
    • 3475-183
    • 2015-002509-13
    • 163146
    • MK-3475-183
    • KEYNOTE-183
    First Posted:
    Oct 15, 2015
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Sep 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 DetailsSubject Disposition as per database cutoff date of August 3, 2020.
    Pre-assignment DetailNote: For administrative reasons (a noncompliant site), one participant in the SOC arm was recorded as "Ongoing in Trial" in the CSR Disposition Table and "Final Disposition Unknown" here.
    Arm/Group TitlePembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Period Title: Overall Study
    STARTED126125
    Treated122123
    COMPLETED00
    NOT COMPLETED126125

    Baseline Characteristics

    Arm/Group TitlePembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+DexamethasoneTotal
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Total of all reporting groups
    Overall Participants126125251
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    65.5
    (9.3)
    66.4
    (10.0)
    65.9
    (9.6)
    Sex: Female, Male (Count of Participants)
    Female
    48
    38.1%
    46
    36.8%
    94
    37.5%
    Male
    78
    61.9%
    79
    63.2%
    157
    62.5%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    8
    6.3%
    5
    4%
    13
    5.2%
    Not Hispanic or Latino
    110
    87.3%
    117
    93.6%
    227
    90.4%
    Unknown or Not Reported
    8
    6.3%
    3
    2.4%
    11
    4.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    17
    13.5%
    12
    9.6%
    29
    11.6%
    Native Hawaiian or Other Pacific Islander
    2
    1.6%
    1
    0.8%
    3
    1.2%
    Black or African American
    10
    7.9%
    14
    11.2%
    24
    9.6%
    White
    92
    73%
    95
    76%
    187
    74.5%
    More than one race
    1
    0.8%
    2
    1.6%
    3
    1.2%
    Unknown or Not Reported
    4
    3.2%
    1
    0.8%
    5
    2%
    Disease Status (Refractory vs. Sensitive to Lenalidomide) (Count of Participants)
    Refractory to Lenalidomide
    108
    85.7%
    108
    86.4%
    216
    86.1%
    Sensitive to Lenalidomide
    18
    14.3%
    17
    13.6%
    35
    13.9%

    Outcome Measures

    1. Primary Outcome
    TitleProgression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria
    DescriptionProgression free survival was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS was assessed by CAC blinded central review according to the IMWG 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. Median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. 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+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Measure Participants126125
    Median (95% Confidence Interval) [Months]
    5.7
    7.4
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Pomalidomide+Dexamethasone, Standard of Care (SOC) Pomalidomide+Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.99324
    Comments
    MethodLog Rank
    CommentsOne-sided p-value based on Stratified log-rank test.
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.50
    Confidence Interval (2-Sided) 95%
    1.08 to 2.08
    Parameter Dispersion Type:
    Value:
    Estimation CommentsBased on Cox regression model with treatment as a covariate stratified by disease status (refractory vs. sensitive to Lenalidomide) and Lines of previous treatments (two vs. three or more).
    2. Primary Outcome
    TitleOverall Survival (OS)
    DescriptionOverall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Median overall survival was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was August 3, 2020.
    Time FrameUp to approximately 54 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+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Measure Participants126125
    Median (95% Confidence Interval) [Months]
    21.0
    39.6
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Pomalidomide+Dexamethasone, Standard of Care (SOC) Pomalidomide+Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.99989
    Comments
    MethodLog Rank
    CommentsOne-sided p-value based on Stratified log-rank test.
    Method of EstimationEstimation ParameterHazard Ratio (HR)
    Estimated Value1.84
    Confidence Interval (2-Sided) 95%
    1.32 to 2.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Other Statistical AnalysisThe Hazard Ratio and 95% confidence intervals were based on Cox regression model with treatment as a covariate stratified by disease status (refractory vs. sensitive to Lenalidomide) and Lines of previous treatments (two vs. three or more).
    3. Secondary Outcome
    TitleOverall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
    DescriptionORR was defined as the percentage of the participants in the analysis population 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 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+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Measure Participants126125
    Number (95% Confidence Interval) [Percentage of participants]
    37.3
    29.6%
    42.4
    33.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Pembrolizumab+Pomalidomide+Dexamethasone, Standard of Care (SOC) Pomalidomide+Dexamethasone
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesisp-Value0.79921
    Comments
    MethodMiettinen & Nurminen method
    Comments
    Method of EstimationEstimation ParameterDifference in % vs. SOC
    Estimated Value-5.2
    Confidence Interval (2-Sided) 95%
    -17.1 to 6.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Other Statistical AnalysisBased on Miettinen & Nurminen method stratified by disease status (refractory vs. sensitive to Lenalidomide) and Lines of previous treatments (two vs. three or more); 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
    TitleParticipants Experiencing One or More Adverse Events (AEs)
    DescriptionAn adverse event (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. Database cutoff was August 3, 2020.
    Time FrameUp to approximately 54 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
    Arm/Group TitlePembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Measure Participants122123
    Count of Participants [Participants]
    122
    96.8%
    119
    95.2%
    5. Secondary Outcome
    TitleParticipants Discontinuing Study Investigational Product Due to an AE
    DescriptionAn adverse event 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. Database cutoff was August 3, 2020.
    Time FrameUp to approximately 54 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.
    Arm/Group TitlePembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Measure Participants122123
    Count of Participants [Participants]
    26
    20.6%
    10
    8%
    6. Secondary Outcome
    TitleDisease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
    DescriptionDisease control rate was the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, minimal response (MR) or have demonstrated stable disease (SD) for at least 12 weeks prior to any evidence of progression. PD was development of or an increase in the size of bone lesions or soft tissue plasmacytomas. 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 FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry/fluorescence; 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+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Measure Participants126125
    Number (95% Confidence Interval) [Percentage of participants]
    88.1
    69.9%
    84.8
    67.8%
    7. 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. As a result of a full clinical hold by FDA that led to discontinuation of study enrollment, no data was collected for analysis of PFS2.
    Time FrameUp to approximately 30 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population was to include all randomized participants. Study treatment was terminated early and no data was collected for analysis of PFS2.
    Arm/Group TitlePembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    Measure Participants00

    Adverse Events

    Time FrameUp to approximately 54 months
    Adverse Event Reporting Description The analysis population for all-cause mortality was all randomized participants and for adverse events was the treated participants. Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered related to study treatment, therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as AEs. The database cutoff date was August 3, 2020.
    Arm/Group TitlePembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Arm/Group DescriptionParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
    All Cause Mortality
    Pembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total86/126 (68.3%) 64/125 (51.2%)
    Serious Adverse Events
    Pembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total79/122 (64.8%) 57/123 (46.3%)
    Blood and lymphatic system disorders
    Anaemia1/122 (0.8%) 14/123 (3.3%) 4
    Anaemia of malignant disease0/122 (0%) 01/123 (0.8%) 1
    Disseminated intravascular coagulation1/122 (0.8%) 10/123 (0%) 0
    Febrile bone marrow aplasia1/122 (0.8%) 10/123 (0%) 0
    Febrile neutropenia4/122 (3.3%) 44/123 (3.3%) 5
    Pancytopenia0/122 (0%) 01/123 (0.8%) 1
    Thrombocytopenia0/122 (0%) 01/123 (0.8%) 1
    Cardiac disorders
    Atrial fibrillation2/122 (1.6%) 21/123 (0.8%) 1
    Cardiac failure1/122 (0.8%) 11/123 (0.8%) 1
    Cardiogenic shock1/122 (0.8%) 10/123 (0%) 0
    Myocardial infarction2/122 (1.6%) 20/123 (0%) 0
    Myocarditis1/122 (0.8%) 20/123 (0%) 0
    Pericardial haemorrhage1/122 (0.8%) 10/123 (0%) 0
    Supraventricular tachycardia1/122 (0.8%) 10/123 (0%) 0
    Ear and labyrinth disorders
    Vertigo1/122 (0.8%) 10/123 (0%) 0
    Vertigo positional1/122 (0.8%) 10/123 (0%) 0
    Endocrine disorders
    Adrenal insufficiency1/122 (0.8%) 10/123 (0%) 0
    Eye disorders
    Cataract0/122 (0%) 01/123 (0.8%) 1
    Gastrointestinal disorders
    Constipation1/122 (0.8%) 10/123 (0%) 0
    Diarrhoea1/122 (0.8%) 11/123 (0.8%) 1
    Ileus1/122 (0.8%) 10/123 (0%) 0
    Inguinal hernia1/122 (0.8%) 10/123 (0%) 0
    Large intestine perforation1/122 (0.8%) 10/123 (0%) 0
    Tooth disorder1/122 (0.8%) 10/123 (0%) 0
    Upper gastrointestinal haemorrhage0/122 (0%) 01/123 (0.8%) 1
    General disorders
    Chest pain1/122 (0.8%) 10/123 (0%) 0
    Death3/122 (2.5%) 30/123 (0%) 0
    Fatigue0/122 (0%) 02/123 (1.6%) 2
    Oedema peripheral0/122 (0%) 01/123 (0.8%) 1
    Pain0/122 (0%) 01/123 (0.8%) 1
    Pyrexia3/122 (2.5%) 35/123 (4.1%) 5
    Hepatobiliary disorders
    Hepatitis1/122 (0.8%) 10/123 (0%) 0
    Infections and infestations
    Anal abscess0/122 (0%) 01/123 (0.8%) 1
    Arthritis bacterial1/122 (0.8%) 10/123 (0%) 0
    Bacteraemia1/122 (0.8%) 10/123 (0%) 0
    Bacterial infection1/122 (0.8%) 10/123 (0%) 0
    Bacterial sepsis1/122 (0.8%) 10/123 (0%) 0
    Bronchitis1/122 (0.8%) 11/123 (0.8%) 1
    Bronchitis bacterial0/122 (0%) 01/123 (0.8%) 1
    Cellulitis2/122 (1.6%) 20/123 (0%) 0
    Clostridium difficile colitis0/122 (0%) 01/123 (0.8%) 1
    Clostridium difficile infection1/122 (0.8%) 10/123 (0%) 0
    Escherichia bacteraemia0/122 (0%) 01/123 (0.8%) 1
    Genital herpes simplex0/122 (0%) 01/123 (0.8%) 1
    Infective exacerbation of chronic obstructive airways disease1/122 (0.8%) 40/123 (0%) 0
    Influenza1/122 (0.8%) 13/123 (2.4%) 3
    Lower respiratory tract infection1/122 (0.8%) 10/123 (0%) 0
    Neutropenic sepsis2/122 (1.6%) 20/123 (0%) 0
    Parainfluenzae virus infection1/122 (0.8%) 10/123 (0%) 0
    Parotitis1/122 (0.8%) 10/123 (0%) 0
    Pneumocystis jirovecii pneumonia3/122 (2.5%) 30/123 (0%) 0
    Pneumonia23/122 (18.9%) 2917/123 (13.8%) 21
    Pneumonia bacterial1/122 (0.8%) 10/123 (0%) 0
    Pneumonia influenzal0/122 (0%) 01/123 (0.8%) 1
    Pneumonia parainfluenzae viral1/122 (0.8%) 10/123 (0%) 0
    Pulmonary sepsis1/122 (0.8%) 10/123 (0%) 0
    Respiratory tract infection1/122 (0.8%) 11/123 (0.8%) 1
    Respiratory tract infection viral1/122 (0.8%) 10/123 (0%) 0
    Rhinovirus infection1/122 (0.8%) 10/123 (0%) 0
    Sepsis3/122 (2.5%) 33/123 (2.4%) 3
    Septic shock2/122 (1.6%) 21/123 (0.8%) 1
    Sinusitis1/122 (0.8%) 11/123 (0.8%) 1
    Subcutaneous abscess0/122 (0%) 01/123 (0.8%) 1
    Upper respiratory tract infection1/122 (0.8%) 13/123 (2.4%) 3
    Urinary tract infection1/122 (0.8%) 11/123 (0.8%) 1
    Viral infection1/122 (0.8%) 10/123 (0%) 0
    Wound infection1/122 (0.8%) 10/123 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose0/122 (0%) 01/123 (0.8%) 1
    Femoral neck fracture0/122 (0%) 01/123 (0.8%) 1
    Femur fracture1/122 (0.8%) 20/123 (0%) 0
    Fibula fracture1/122 (0.8%) 10/123 (0%) 0
    Hip fracture1/122 (0.8%) 10/123 (0%) 0
    Infusion related reaction1/122 (0.8%) 10/123 (0%) 0
    Muscle strain1/122 (0.8%) 10/123 (0%) 0
    Post procedural fever1/122 (0.8%) 10/123 (0%) 0
    Subdural haematoma1/122 (0.8%) 10/123 (0%) 0
    Upper limb fracture0/122 (0%) 01/123 (0.8%) 1
    Investigations
    Alanine aminotransferase increased1/122 (0.8%) 10/123 (0%) 0
    Aspartate aminotransferase increased1/122 (0.8%) 10/123 (0%) 0
    Neutrophil count decreased2/122 (1.6%) 20/123 (0%) 0
    Metabolism and nutrition disorders
    Dehydration0/122 (0%) 02/123 (1.6%) 2
    Gout0/122 (0%) 01/123 (0.8%) 2
    Hypercalcaemia2/122 (1.6%) 31/123 (0.8%) 1
    Hypokalaemia1/122 (0.8%) 11/123 (0.8%) 1
    Hyponatraemia1/122 (0.8%) 10/123 (0%) 0
    Hypovolaemia0/122 (0%) 01/123 (0.8%) 1
    Steroid diabetes0/122 (0%) 01/123 (0.8%) 1
    Musculoskeletal and connective tissue disorders
    Fracture pain0/122 (0%) 01/123 (0.8%) 1
    Muscular weakness1/122 (0.8%) 10/123 (0%) 0
    Osteonecrosis of jaw1/122 (0.8%) 10/123 (0%) 0
    Pathological fracture1/122 (0.8%) 13/123 (2.4%) 4
    Polyarthritis1/122 (0.8%) 10/123 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma1/122 (0.8%) 21/123 (0.8%) 1
    Basosquamous carcinoma of skin1/122 (0.8%) 10/123 (0%) 0
    Colorectal adenocarcinoma1/122 (0.8%) 10/123 (0%) 0
    Intestinal adenocarcinoma1/122 (0.8%) 10/123 (0%) 0
    Malignant ascites1/122 (0.8%) 10/123 (0%) 0
    Squamous cell carcinoma2/122 (1.6%) 21/123 (0.8%) 1
    Squamous cell carcinoma of skin1/122 (0.8%) 10/123 (0%) 0
    Nervous system disorders
    Balance disorder1/122 (0.8%) 10/123 (0%) 0
    Central nervous system lesion0/122 (0%) 01/123 (0.8%) 1
    Cerebral haemorrhage1/122 (0.8%) 10/123 (0%) 0
    Cerebrovascular accident2/122 (1.6%) 21/123 (0.8%) 1
    Cognitive disorder0/122 (0%) 01/123 (0.8%) 1
    IIIrd nerve disorder1/122 (0.8%) 10/123 (0%) 0
    Seizure0/122 (0%) 01/123 (0.8%) 1
    Somnolence0/122 (0%) 01/123 (0.8%) 1
    Syncope1/122 (0.8%) 10/123 (0%) 0
    Psychiatric disorders
    Delirium0/122 (0%) 01/123 (0.8%) 1
    Renal and urinary disorders
    Acute kidney injury4/122 (3.3%) 44/123 (3.3%) 4
    Chronic kidney disease1/122 (0.8%) 10/123 (0%) 0
    Cystitis haemorrhagic0/122 (0%) 01/123 (0.8%) 1
    Renal failure2/122 (1.6%) 22/123 (1.6%) 2
    Respiratory, thoracic and mediastinal disorders
    Acute pulmonary oedema1/122 (0.8%) 10/123 (0%) 0
    Acute respiratory failure1/122 (0.8%) 11/123 (0.8%) 1
    Asthma1/122 (0.8%) 10/123 (0%) 0
    Chronic obstructive pulmonary disease2/122 (1.6%) 20/123 (0%) 0
    Cough0/122 (0%) 01/123 (0.8%) 1
    Dyspnoea1/122 (0.8%) 12/123 (1.6%) 2
    Haemoptysis0/122 (0%) 01/123 (0.8%) 1
    Hypoxia1/122 (0.8%) 11/123 (0.8%) 1
    Interstitial lung disease1/122 (0.8%) 10/123 (0%) 0
    Pleural effusion1/122 (0.8%) 10/123 (0%) 0
    Pneumonitis5/122 (4.1%) 50/123 (0%) 0
    Pulmonary congestion0/122 (0%) 01/123 (0.8%) 1
    Pulmonary embolism0/122 (0%) 04/123 (3.3%) 4
    Pulmonary haemorrhage1/122 (0.8%) 10/123 (0%) 0
    Skin and subcutaneous tissue disorders
    Panniculitis1/122 (0.8%) 10/123 (0%) 0
    Rash0/122 (0%) 01/123 (0.8%) 1
    Stevens-Johnson syndrome1/122 (0.8%) 10/123 (0%) 0
    Vascular disorders
    Aortic stenosis0/122 (0%) 01/123 (0.8%) 1
    Deep vein thrombosis0/122 (0%) 01/123 (0.8%) 1
    Hypotension1/122 (0.8%) 11/123 (0.8%) 1
    Orthostatic hypotension0/122 (0%) 01/123 (0.8%) 1
    Other (Not Including Serious) Adverse Events
    Pembrolizumab+Pomalidomide+DexamethasoneStandard of Care (SOC) Pomalidomide+Dexamethasone
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total115/122 (94.3%) 114/123 (92.7%)
    Blood and lymphatic system disorders
    Anaemia34/122 (27.9%) 5340/123 (32.5%) 57
    Leukopenia10/122 (8.2%) 219/123 (7.3%) 16
    Neutropenia49/122 (40.2%) 12033/123 (26.8%) 63
    Thrombocytopenia26/122 (21.3%) 4919/123 (15.4%) 27
    Gastrointestinal disorders
    Constipation30/122 (24.6%) 3726/123 (21.1%) 27
    Diarrhoea21/122 (17.2%) 3027/123 (22%) 35
    Gastrooesophageal reflux disease4/122 (3.3%) 47/123 (5.7%) 7
    Nausea23/122 (18.9%) 2616/123 (13%) 19
    Vomiting10/122 (8.2%) 1713/123 (10.6%) 14
    General disorders
    Asthenia15/122 (12.3%) 2114/123 (11.4%) 17
    Chest pain9/122 (7.4%) 115/123 (4.1%) 6
    Fatigue33/122 (27%) 3637/123 (30.1%) 44
    Oedema peripheral22/122 (18%) 2520/123 (16.3%) 23
    Pyrexia26/122 (21.3%) 3519/123 (15.4%) 23
    Infections and infestations
    Nasopharyngitis7/122 (5.7%) 76/123 (4.9%) 8
    Pneumonia7/122 (5.7%) 72/123 (1.6%) 2
    Upper respiratory tract infection21/122 (17.2%) 2725/123 (20.3%) 33
    Urinary tract infection1/122 (0.8%) 18/123 (6.5%) 9
    Investigations
    Alanine aminotransferase increased10/122 (8.2%) 114/123 (3.3%) 4
    Blood creatinine increased7/122 (5.7%) 104/123 (3.3%) 4
    Neutrophil count decreased16/122 (13.1%) 2817/123 (13.8%) 26
    Platelet count decreased7/122 (5.7%) 1110/123 (8.1%) 12
    Weight decreased7/122 (5.7%) 75/123 (4.1%) 5
    White blood cell count decreased13/122 (10.7%) 1911/123 (8.9%) 21
    Metabolism and nutrition disorders
    Decreased appetite9/122 (7.4%) 98/123 (6.5%) 8
    Hyperglycaemia7/122 (5.7%) 75/123 (4.1%) 5
    Hypokalaemia11/122 (9%) 168/123 (6.5%) 9
    Hypomagnesaemia3/122 (2.5%) 68/123 (6.5%) 8
    Musculoskeletal and connective tissue disorders
    Arthralgia10/122 (8.2%) 1116/123 (13%) 17
    Back pain14/122 (11.5%) 1521/123 (17.1%) 23
    Muscle spasms15/122 (12.3%) 1614/123 (11.4%) 15
    Muscular weakness6/122 (4.9%) 1011/123 (8.9%) 13
    Musculoskeletal chest pain12/122 (9.8%) 146/123 (4.9%) 6
    Pain in extremity6/122 (4.9%) 87/123 (5.7%) 7
    Nervous system disorders
    Dizziness16/122 (13.1%) 1914/123 (11.4%) 15
    Headache16/122 (13.1%) 205/123 (4.1%) 7
    Neuropathy peripheral8/122 (6.6%) 85/123 (4.1%) 5
    Tremor10/122 (8.2%) 1110/123 (8.1%) 10
    Psychiatric disorders
    Depression7/122 (5.7%) 73/123 (2.4%) 3
    Insomnia10/122 (8.2%) 1117/123 (13.8%) 18
    Respiratory, thoracic and mediastinal disorders
    Cough19/122 (15.6%) 2318/123 (14.6%) 21
    Dyspnoea21/122 (17.2%) 2619/123 (15.4%) 25
    Epistaxis9/122 (7.4%) 93/123 (2.4%) 5
    Skin and subcutaneous tissue disorders
    Pruritus6/122 (4.9%) 610/123 (8.1%) 10
    Rash12/122 (9.8%) 1310/123 (8.1%) 12

    Limitations/Caveats

    The MK-3475-183 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:
    NCT02576977
    Other Study ID Numbers:
    • 3475-183
    • 2015-002509-13
    • 163146
    • MK-3475-183
    • KEYNOTE-183
    First Posted:
    Oct 15, 2015
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Sep 1, 2021