Clincosm LogoSign in Get a demo

A Study of Pembrolizumab (MK-3475) in Combination With Standard of Care Treatments in Participants With Multiple Myeloma (MK-3475-023/KEYNOTE-023)

Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Terminated
CT.gov ID
NCT02036502
Collaborator
(none)
77
Enrollment
8
Arms
73.1
Actual Duration (Months)

Study Details

Study Description

Brief Summary

This is a study of pembrolizumab (MK-3475) in combination with lenalidomide and low-dose dexamethasone in participants with refractory or relapsed and refractory Multiple Myeloma (rrMM), and in combination with carfilzomib and low-dose dexamethasone in participants with relapsed or refractory Multiple Myeloma (rMM).

This study was being done to find the maximum tolerated dose (MTD)/maximum administered dose (MAD) and recommended Phase 2 dose (RP2D), and to evaluate the safety and tolerability of pembrolizumab when given in combination with standard of care (SOC) treatments in participants with rrMM or rMM. Preliminary efficacy data will also be assessed. There was no primary hypothesis associated with this study.

On 03-Jul-2017, the United States Food and Drug Administration (US FDA) placed the rrMM cohort of this protocol on clinical hold based on safety data from two other pembrolizumab protocols: MK-3475-183 (NCT02576977) and MK-3475-185 (NCT02579863) presented to the Data Monitoring Committee.

On 15-Sep-2017, the US FDA placed the rMM cohort of this study on partial clinical hold. Enrollment was stopped and will not be reopened. Participants who are deriving clinical benefit were allowed to continue receiving study treatment until protocol-specific end of treatment, and then progress into long term safety and survival follow up. Participants who are not deriving clinical benefit, must stop study treatment and move into the long term safety and survival follow up.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Actual Enrollment :
77 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Multi-Cohort Trial of Pembrolizumab (MK-3475) in Combination With Backbone Treatments for Subjects With Multiple Myeloma
Actual Study Start Date :
Feb 14, 2014
Actual Primary Completion Date :
Mar 19, 2020
Actual Study Completion Date :
Mar 19, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 1:pembro 2mg/kg+len 25mg+dex 40 mg

Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle).

Biological: Pembrolizumab
Intravenous (IV) infusion
Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Lenalidomide
    Oral capsule
    Other Names:
  • REVLIMID®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    		•
    Experimental: Part 1:pembro 2mg/kg+len 10 mg+dex 40 mg

    Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle).

    Biological: Pembrolizumab
    Intravenous (IV) infusion
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Lenalidomide
    Oral capsule
    Other Names:
  • REVLIMID®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    		•
    Experimental: Part 2:pembro 200 mg+len 25 mg+dex 40 mg

    Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle).

    Biological: Pembrolizumab
    Intravenous (IV) infusion
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Lenalidomide
    Oral capsule
    Other Names:
  • REVLIMID®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    		•
    Experimental: Part 2:pembro 200 mg+len 25 mg+dex 20 mg

    Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28- day cycle).

    Biological: Pembrolizumab
    Intravenous (IV) infusion
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Lenalidomide
    Oral capsule
    Other Names:
  • REVLIMID®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    		•
    Experimental: Part 2:pembro 200 mg+len 10 mg+dex 40 mg

    Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle).

    Biological: Pembrolizumab
    Intravenous (IV) infusion
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Lenalidomide
    Oral capsule
    Other Names:
  • REVLIMID®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    		•
    Experimental: Part 3:pembro 200 mg+len 25 mg+dex 40 mg

    Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W weekly during each 28-day cycle.

    Biological: Pembrolizumab
    Intravenous (IV) infusion
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Lenalidomide
    Oral capsule
    Other Names:
  • REVLIMID®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    		•
    Experimental: Part 3:pembro 200 mg+len 25 mg+dex 20 mg

    Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W weekly during each 28-day cycle.

    Biological: Pembrolizumab
    Intravenous (IV) infusion
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Lenalidomide
    Oral capsule
    Other Names:
  • REVLIMID®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    		•
    Experimental: Part 3:pembro 200 mg+carf 56 mg/m^2+dex 20 mg

    Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg once or twice weekly (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.

    Biological: Pembrolizumab
    Intravenous (IV) infusion
    Other Names:
  • MK-3475
  • KEYTRUDA®

    • Drug: Dexamethasone
    Oral tablet IV infusion
    Other Names:
  • DECADRON®

    • Drug: Carfilzomib
    IV infusion
    Other Names:
  • KYPROLIS®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0) [Up to 28 days in Cycle 1]

      DLTs were assessed during Cycle 1 (28 days) and were defined as the occurrence of any of the following judged by the investigator to be possibly, probably or definitely related to study drug: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days; Gr 3 non-hematologic toxicity lasting >3 days; Gr 3 non-hematologic laboratory value if: medical intervention was required, abnormality led to hospitalization, was renal or liver function related, or persisted for >1 week; Gr 3/4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (associated with bleeding requiring platelet transfusion or life-threatening bleeding); Gr 5 toxicity; or delay of >1 week in initiating Cycle 2 or unable to complete 80% of treatment during the first course of therapy due to drug-related toxicity. DLTs for the rMM cohort were any drug-related adverse events that cannot be managed by dose modification. DLTs are reported for the maximum tolerated dose.

    2. Number of Participants Who Experienced One or More Adverse Events (AEs) [Up to approximately 72.7 months]

      An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.

    3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Up to approximately 72.7 months]

      An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.

    Secondary Outcome Measures

    1. Objective Response Rate (ORR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment [Up to approximately 72.7 months]

      ORR was the percentage of the participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR = ≥50% reduction of serum M-protein+reduction in 24hr urinary M-protein by ≥90% or to <200 mg/24 hrs.

    2. Disease Control Rate (DCR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment [Up to approximately 72.7 months]

      DCR was the percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or stable disease (SD) ≥12 weeks prior to evidence of disease progression (PD). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+ ≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not on electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR=≥50% reduction of serum M-protein+reduction in 24 hr urinary M-protein by ≥90% or to <200 mg/24 hrs; SD=not meeting the criteria for CR, VGPR, PR, or PD. PD=≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas.

    Other Outcome Measures

    1. Duration of Response (DOR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment [Up to approximately 72.7 months]

      DOR was the time from first evidence of response (stringent complete response [sCR]+complete response [CR], very good partial response [VGPR], partial response [PR]) until disease progression (PD) or death. CR=negative immunofixation of serum and urine+no tissue plasmacytomas+≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR = ≥50% reduction of serum M-protein+reduction in 24hr urinary M-protein by ≥90% or to <200 mg/24 hrs. PD=≥1 of the following: ≥25% increase from baseline serum/urine M-protein; hypercalcemia; increase between involved/uninvolved FLC levels; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas. DOR was calculated using the Kaplan-Meier method for censored data.

    2. Overall Survival (OS) [Up to approximately 72.7 months]

      OS was defined as the time from randomization to death due to any cause. OS was calculated from 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.

    3. Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment [Up to approximately 72.7 months]

      PFS was defined as the time from randomization to the first documented disease progression (PD) or death due to any cause. PD= ≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas. The median PFS was calculated from the Kaplan-Meier method for censored data.

    4. Time to Progression (TTP) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment [Up to approximately 72.7 months]

      TTP was defined as the time from the first dose to first documented disease progression (PD) or death due to any cause. PD= ≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    All Participants:

    • Confirmed diagnosis of multiple myeloma (MM)

    • MM with measurable disease

    • Archival or newly obtained bone marrow material available. In addition, for participants in the United States (US) and Canada, able to provide newly obtained bone marrow aspirate for biomarker analysis.

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

    • Adequate organ function

    • Female participants of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment

    • Male participants must agree to use a latex condom during sexual contact with females of childbearing potential even if they have had a successful vasectomy starting with the first dose of study treatment through 120 days after the last dose of study treatment

    • Able to swallow capsules and able to take or tolerate oral medications on a continuous basis

    Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:

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

    • Prior anti-myeloma treatments must have included an immunomodulatory (IMiD) treatment (lenalidomide, pomalidomide or thalidomide) AND proteasome inhibitor (bortezomib or carfilzomib) alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor

    • Must agree to follow the regional requirements for lenalidomide counseling, pregnancy testing, and birth control; willing and able to comply with the regional requirements (for example, periodic pregnancy tests and safety labs)

    Cohort 2 Participants:

    • MM with relapsing or refractory disease at study entry

    • Received prior treatment with 1 to 3 lines for MM

    • Achieved a partial response to at least one prior regimen (defined as ≥50% decrease in tumor burden)

    • Left ventricular ejection fraction of at least 40%

    Exclusion Criteria:
    All Participants:

    • Currently participating in and receiving study therapy or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment

    • History of repeated infections; primary amyloidosis; hyperviscosity; plasma cell leukemia; polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome or Waldenström's macroglobulinemia

    • Diagnosis of immunosuppressive disorder or on any other immunosuppressive therapy within 7 days prior to the first dose of study treatment

    • Received a prior monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e. ≤ Grade 1 or at baseline) from a baseline AE or a Grade 1 AE associated with agents administered more than 4 weeks earlier

    • Prior anti-MM therapy (including dexamethasone), targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from AEs due to a previously administered agent

    • An additional malignancy that is progressing or requires active treatment within the last 5 years

    • Active autoimmune disease or a documented history of autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents

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

    • Active infection requiring intravenous systemic therapy

    • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study

    • Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment

    • Prior therapy with an anti-programmed cell death (PD)-1, anti-PD ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137 antibody, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody

    • Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection

    • Clinically significant coagulopathy

    • Has had or is planning for allogeneic stem cell transplant

    • Autologous stem cell transplant within 12 weeks before the first infusion

    • History of Grade 4 rash associated with thalidomide treatment

    • Known hypersensitivity to thalidomide, lenalidomide or pomalidomide

    • Received a live vaccine within 30 days of planned start of study treatment

    Dose Determination Arm, Dose Confirmation Arm and Cohort 1 Participants:

    • Clinically active central nervous system (CNS) involvement

    • Known gastrointestinal disease that may significantly alter the absorption of lenalidomide

    • Unable or unwilling to undergo antithrombotic prophylactic treatment

    • Known symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

    Cohort 2 Participants:

    • Smoldering MM (SMM), monoclonal gammopathy of undetermined significance (MGUS), plasma cell leukemia or Waldenström's macroglobulinemia

    • Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to the first dose of study treatment

    • Myocardial infarction within 4 months prior to randomization, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker.

    • Known history of allergy to CAPTISOL® (a cyclodextrin derivative used to solubilize carfilzomib)

    • Hypersensitivity to carfilzomib, bortezomib, boron, or mannitol

    • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment

    • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to the first dose of study treatment

    • Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to the first dose of study treatment

    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

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Merck Sharp & Dohme LLC
    ClinicalTrials.gov Identifier:
    NCT02036502
    Other Study ID Numbers:
    • 3475-023
    • 2013-003512-44
    • MK-3475-023
    • KEYNOTE-023
    First Posted:
    Jan 15, 2014
    Last Update Posted:
    Apr 8, 2021
    Last Verified:
    Mar 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
    PDL1
    PD-L1
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Dexamethasone
    Pembrolizumab
    Lenalidomide

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This study included 3 parts: (1) dose determination/escalation (2) dose confirmation and (3) dose expansion. The study included a pooled analysis of efficacy for participants receiving any dose of pembro+len+dex combined or pembro+carfilzomib (carf)+dex randomized by disease cohort.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Period Title: Part 1:Dose Determination/Escalation
    STARTED 6 4 0 0 0 0 0 0
    Treated 6 3 0 0 0 0 0 0
    COMPLETED 0 0 0 0 0 0 0 0
    NOT COMPLETED 6 4 0 0 0 0 0 0
    Period Title: Part 1:Dose Determination/Escalation
    STARTED 0 0 6 2 1 0 0 0
    Treated 0 0 6 1 1 0 0 0
    COMPLETED 0 0 0 0 0 0 0 0
    NOT COMPLETED 0 0 6 2 1 0 0 0
    Period Title: Part 1:Dose Determination/Escalation
    STARTED 0 0 0 0 0 47 1 10
    Treated 0 0 0 0 0 45 1 10
    COMPLETED 0 0 0 0 0 0 0 0
    NOT COMPLETED 0 0 0 0 0 47 1 10

    Baseline Characteristics

    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg Total
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Total of all reporting groups
    Overall Participants 6 4 6 2 1 47 1 10 77
    Age, Customized (Count of Participants)
    0 to 17 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    18 to 64 years
    4
    66.7%
    2
    50%
    5
    83.3%
    0
    0%
    0
    0%
    28
    59.6%
    0
    0%
    8
    80%
    47
    61%
    65 to 84 years
    2
    33.3%
    2
    50%
    1
    16.7%
    2
    100%
    1
    100%
    19
    40.4%
    1
    100%
    1
    10%
    29
    37.7%
    85 years and over
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    10%
    1
    1.3%
    Sex: Female, Male (Count of Participants)
    Female
    1
    16.7%
    1
    25%
    2
    33.3%
    1
    50%
    0
    0%
    21
    44.7%
    1
    100%
    4
    40%
    31
    40.3%
    Male
    5
    83.3%
    3
    75%
    4
    66.7%
    1
    50%
    1
    100%
    26
    55.3%
    0
    0%
    6
    60%
    46
    59.7%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    33.3%
    3
    75%
    0
    0%
    0
    0%
    0
    0%
    6
    12.8%
    0
    0%
    2
    20%
    13
    16.9%
    Not Hispanic or Latino
    4
    66.7%
    1
    25%
    4
    66.7%
    2
    100%
    1
    100%
    36
    76.6%
    1
    100%
    2
    20%
    51
    66.2%
    Unknown or Not Reported
    0
    0%
    0
    0%
    2
    33.3%
    0
    0%
    0
    0%
    5
    10.6%
    0
    0%
    6
    60%
    13
    16.9%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    2.1%
    0
    0%
    0
    0%
    1
    1.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    7
    14.9%
    0
    0%
    0
    0%
    8
    10.4%
    White
    6
    100%
    4
    100%
    5
    83.3%
    2
    100%
    1
    100%
    39
    83%
    1
    100%
    10
    100%
    68
    88.3%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
    Description DLTs were assessed during Cycle 1 (28 days) and were defined as the occurrence of any of the following judged by the investigator to be possibly, probably or definitely related to study drug: Grade (Gr) 4 non-hematologic toxicity; Gr 4 hematologic toxicity lasting ≥7 days; Gr 3 non-hematologic toxicity lasting >3 days; Gr 3 non-hematologic laboratory value if: medical intervention was required, abnormality led to hospitalization, was renal or liver function related, or persisted for >1 week; Gr 3/4 febrile neutropenia; thrombocytopenia <25,000 cells/mm^3 (associated with bleeding requiring platelet transfusion or life-threatening bleeding); Gr 5 toxicity; or delay of >1 week in initiating Cycle 2 or unable to complete 80% of treatment during the first course of therapy due to drug-related toxicity. DLTs for the rMM cohort were any drug-related adverse events that cannot be managed by dose modification. DLTs are reported for the maximum tolerated dose.
    Time Frame Up to 28 days in Cycle 1

    Outcome Measure Data

    Analysis Population Description
    All DLT-evaluable participants in Parts 1 and 2 who received ≥1 dose of study treatment, completed Cycle 1 (28 days), or who had a DLT during the DLT evaluation period. Per protocol, DLT was not planned to be evaluated in Part 3.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 6 3 6 1 1 0 0 0
    Count of Participants [Participants]
    3
    50%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title Number of Participants Who Experienced One or More Adverse Events (AEs)
    Description An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received ≥1 dose of study treatment.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 6 3 6 1 1 45 1 10
    Count of Participants [Participants]
    6
    100%
    3
    75%
    6
    100%
    1
    50%
    1
    100%
    45
    95.7%
    1
    100%
    10
    100%
    3. Primary Outcome
    Title Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
    Description An adverse event was defined as any untoward medical occurrence in a participant administered study treatment and did not necessarily have a causal relationship with this treatment. An adverse event could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that was temporally associated with the use of the study treatment was also an adverse event.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received ≥1 dose of study treatment.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 6 3 6 1 1 45 1 10
    Count of Participants [Participants]
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    4
    8.5%
    0
    0%
    6
    60%
    4. Secondary Outcome
    Title Objective Response Rate (ORR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
    Description ORR was the percentage of the participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR = ≥50% reduction of serum M-protein+reduction in 24hr urinary M-protein by ≥90% or to <200 mg/24 hrs.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received ≥1 dose of study treatment. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (rrMM or rMM) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg Pooled rrMM Cohort Pooled rMM Cohort
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Participants from Parts 1 and 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received any dose combination of pembrolizumab Q2W (Days 1 and 15) in combination with lenalidomide and dexamethasone Q1W during each 28-day cycle. Participants from Part 2 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 0 0 0 0 0 0 0 0 63 10
    Number (95% Confidence Interval) [Percentage of participants]
    30.2
    503.3%
    70.0
    1750%
    5. Secondary Outcome
    Title Disease Control Rate (DCR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
    Description DCR was the percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), or stable disease (SD) ≥12 weeks prior to evidence of disease progression (PD). CR=negative immunofixation of serum and urine+no tissue plasmacytomas+ ≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not on electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR=≥50% reduction of serum M-protein+reduction in 24 hr urinary M-protein by ≥90% or to <200 mg/24 hrs; SD=not meeting the criteria for CR, VGPR, PR, or PD. PD=≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received ≥1 dose of study treatment. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (rrMM or rMM) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg Pooled rrMM Cohort Pooled rMM Cohort
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Participants from Parts 1 and 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received any dose combination of pembrolizumab Q2W (Days 1 and 15) in combination with lenalidomide and dexamethasone Q1W during each 28-day cycle. Participants from Part 2 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 0 0 0 0 0 0 0 0 63 10
    Number (95% Confidence Interval) [Percentage of participants]
    84.1
    1401.7%
    100.0
    2500%
    6. Other Pre-specified Outcome
    Title Duration of Response (DOR) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
    Description DOR was the time from first evidence of response (stringent complete response [sCR]+complete response [CR], very good partial response [VGPR], partial response [PR]) until disease progression (PD) or death. CR=negative immunofixation of serum and urine+no tissue plasmacytomas+≤5% plasmacytomas in bone marrow; sCR=stringent complete response, CR+normal free light chain (FLC) ratio+no clonal cells in bone marrow; VGPR=serum+urine M-protein detectable by immunofixation but not electrophoresis OR ≥90% reduction in serum M-protein+urine M-protein <100 mg/24 hour(hr); PR = ≥50% reduction of serum M-protein+reduction in 24hr urinary M-protein by ≥90% or to <200 mg/24 hrs. PD=≥1 of the following: ≥25% increase from baseline serum/urine M-protein; hypercalcemia; increase between involved/uninvolved FLC levels; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas. DOR was calculated using the Kaplan-Meier method for censored data.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received ≥1 dose of study treatment and demonstrated at least a partial response. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (rrMM or rMM) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg Pooled rrMM Cohort Pooled rMM Cohort
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Participants from Parts 1 and 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received any dose combination of pembrolizumab Q2W (Days 1 and 15) in combination with lenalidomide and dexamethasone Q1W during each 28-day cycle. Participants from Part 2 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 0 0 0 0 0 0 0 0 19 7
    Median (95% Confidence Interval) [Months]
    16.4
    14.1
    7. Other Pre-specified Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from randomization to death due to any cause. OS was calculated from 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.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received ≥1 dose of study treatment. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (rrMM or rMM) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg Pooled rrMM Cohort Pooled rMM Cohort
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Participants from Parts 1 and 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received any dose combination of pembrolizumab Q2W (Days 1 and 15) in combination with lenalidomide and dexamethasone Q1W during each 28-day cycle. Participants from Part 2 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 0 0 0 0 0 0 0 0 63 10
    Median (95% Confidence Interval) [Months]
    29.0
    22.5
    8. Other Pre-specified Outcome
    Title Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
    Description PFS was defined as the time from randomization to the first documented disease progression (PD) or death due to any cause. PD= ≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas. The median PFS was calculated from the Kaplan-Meier method for censored data.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    The analysis population included all participants who received ≥1 dose of study treatment. The analysis was pre-specified to be a pooled analysis of all participants grouped by disease cohort (rrMM or rMM) and treatment combination (irrespective of dose); therefore data by individual dose were not analyzed.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg Pooled rrMM Cohort Pooled rMM Cohort
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Participants from Parts 1 and 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received any dose combination of pembrolizumab Q2W (Days 1 and 15) in combination with lenalidomide and dexamethasone Q1W during each 28-day cycle. Participants from Part 2 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 0 0 0 0 0 0 0 0 63 10
    Median (95% Confidence Interval) [Months]
    5.6
    14.3
    9. Other Pre-specified Outcome
    Title Time to Progression (TTP) Evaluated According to the International Myeloma Working Group (IMWG) 2006 Response Criteria by Confirmed Investigator Assessment
    Description TTP was defined as the time from the first dose to first documented disease progression (PD) or death due to any cause. PD= ≥1 of the following: ≥25% increase from baseline in serum/urine M-protein; hypercalcemia; increase in FLC ratio; ≥10% bone marrow plasma cells; new or increase in the size of existing bone lesions or tissue plasmacytomas.
    Time Frame Up to approximately 72.7 months

    Outcome Measure Data

    Analysis Population Description
    All participants who received ≥1 dose of study treatment. The analysis was pre-specified to be a pooled analysis of participants grouped by disease cohort (rrMM or rMM)/treatment (irrespective of dose). There were insufficient data available to conduct the TTP analyses.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg Pooled rrMM Cohort Pooled rMM Cohort
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle. Participants from Parts 1 and 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received any dose combination of pembrolizumab Q2W (Days 1 and 15) in combination with lenalidomide and dexamethasone Q1W during each 28-day cycle. Participants from Part 2 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    Measure Participants 0 0 0 0 0 0 0 0 0 0

    Adverse Events

    Time Frame Up to approximately 72.7 months
    Adverse Event Reporting Description The analysis population for adverse events (AEs) consisted of all participants who received ≥1 dose of study treatment. Per protocol, disease progression was not considered an AE unless considered related to study treatment. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "neoplasm progression", "malignant neoplasm progression" and "disease progression" not related to study treatment are excluded. All-cause mortality is reported for all randomized participants.
    Arm/Group Title Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Arm/Group Description Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg once every 2 weeks (Q2W) (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg once weekly (Q1W) during Cycle 1 (28-day cycle). Participants in Part 1 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 2 mg/kg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 2 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 10 mg (Days 1-21) and dexamethasone 40 mg Q1W during Cycle 1 (28-day cycle). Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 40 mg Q1W during each 28-day cycle. Participants in Part 3 with refractory or relapsed and refractory multiple myeloma (rrMM) received pembrolizumab 200 mg Q2W (Days 1 and 15) in combination with lenalidomide 25 mg (Days 1-21) and dexamethasone 20 mg Q1W during each 28-day cycle. Participants in Part 3 with relapsed or refractory multiple myeloma (rMM) received pembrolizumab 200 mg Q3W in combination with carfilzomib 56 mg/m^2 (Days 1, 2, 8, 9, 15, 16) and dexamethasone 20 mg (Days 1, 2, 8, 9, 15, 16, 22, 23) during each 28-day cycle.
    All Cause Mortality
    Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/6 (50%) 3/4 (75%) 1/6 (16.7%) 0/2 (0%) 0/1 (0%) 31/47 (66%) 0/1 (0%) 6/10 (60%)
    Serious Adverse Events
    Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/6 (33.3%) 3/3 (100%) 2/6 (33.3%) 1/1 (100%) 1/1 (100%) 19/45 (42.2%) 0/1 (0%) 9/10 (90%)
    Blood and lymphatic system disorders
    Anaemia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Febrile neutropenia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 4/45 (8.9%) 4 0/1 (0%) 0 0/10 (0%) 0
    Pancytopenia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Thrombocytopenia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Cardiac disorders
    Atrial fibrillation 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Cardiac amyloidosis 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Cardiac failure congestive 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Endocrine disorders
    Hypopituitarism 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Gastrointestinal disorders
    Colitis ischaemic 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Dysphagia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    General disorders
    Death 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Multiple organ dysfunction syndrome 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Hepatobiliary disorders
    Hepatocellular injury 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Liver injury 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Venoocclusive liver disease 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Infections and infestations
    Bacteraemia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Bronchitis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Infection 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Influenza 0/6 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Lower respiratory tract infection 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Pneumonia 1/6 (16.7%) 1 1/3 (33.3%) 3 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 5/45 (11.1%) 6 0/1 (0%) 0 5/10 (50%) 5
    Respiratory tract infection 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Sepsis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Septic shock 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Upper respiratory tract infection 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/1 (100%) 1 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Varicella 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    West Nile viral infection 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Investigations
    Transaminases increased 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Metabolism and nutrition disorders
    Hypercalcaemia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Hyperglycaemia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Tumour lysis syndrome 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Musculoskeletal and connective tissue disorders
    Bone pain 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Musculoskeletal pain 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Nervous system disorders
    Headache 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Ischaemic stroke 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Transient ischaemic attack 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 1/10 (10%) 1
    Renal failure 2/6 (33.3%) 2 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Reproductive system and breast disorders
    Prostatitis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Respiratory, thoracic and mediastinal disorders
    Chronic obstructive pulmonary disease 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Other (Not Including Serious) Adverse Events
    Part 1:Pembro 2mg/kg+Len 25mg+Dex 40 mg Part 1:Pembro 2mg/kg+Len 10 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 2:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 2:Pembro 200 mg+Len 10 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 40 mg Part 3:Pembro 200 mg+Len 25 mg+Dex 20 mg Part 3:Pembro 200 mg+Carf 56 mg/m^2 +Dex 20 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/6 (100%) 3/3 (100%) 6/6 (100%) 1/1 (100%) 1/1 (100%) 44/45 (97.8%) 1/1 (100%) 10/10 (100%)
    Blood and lymphatic system disorders
    Anaemia 4/6 (66.7%) 5 0/3 (0%) 0 2/6 (33.3%) 4 1/1 (100%) 1 0/1 (0%) 0 17/45 (37.8%) 32 1/1 (100%) 1 5/10 (50%) 11
    Neutropenia 4/6 (66.7%) 18 2/3 (66.7%) 4 2/6 (33.3%) 16 1/1 (100%) 5 0/1 (0%) 0 17/45 (37.8%) 45 1/1 (100%) 1 2/10 (20%) 3
    Thrombocytopenia 4/6 (66.7%) 36 1/3 (33.3%) 1 2/6 (33.3%) 5 0/1 (0%) 0 1/1 (100%) 1 18/45 (40%) 38 1/1 (100%) 1 3/10 (30%) 5
    Cardiac disorders
    Atrial fibrillation 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 1/10 (10%) 1
    Cardiac amyloidosis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Cardiomyopathy 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Palpitations 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Ear and labyrinth disorders
    Tinnitus 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 2/10 (20%) 2
    Ear pain 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Vertigo 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Excessive cerumen production 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 1/1 (100%) 1 0/10 (0%) 0
    Endocrine disorders
    Hypothyroidism 1/6 (16.7%) 1 1/3 (33.3%) 2 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 4/45 (8.9%) 4 0/1 (0%) 0 1/10 (10%) 1
    Adrenal insufficiency 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Primary hypothyroidism 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Hyperthyroidism 0/6 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Thyroiditis 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Eye disorders
    Blindness 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Dry eye 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 4/45 (8.9%) 5 0/1 (0%) 0 0/10 (0%) 0
    Eyelid oedema 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Lacrimation increased 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 3/45 (6.7%) 5 0/1 (0%) 0 0/10 (0%) 0
    Vision blurred 0/6 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 3 0/1 (0%) 0 1/1 (100%) 5 4/45 (8.9%) 9 0/1 (0%) 0 0/10 (0%) 0
    Visual acuity reduced 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Ocular hyperaemia 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Eyelid sensory disorder 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 1/1 (100%) 1 0/10 (0%) 0
    Gastrointestinal disorders
    Abdominal pain upper 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Constipation 2/6 (33.3%) 3 0/3 (0%) 0 2/6 (33.3%) 2 1/1 (100%) 1 0/1 (0%) 0 8/45 (17.8%) 21 0/1 (0%) 0 1/10 (10%) 1
    Diarrhoea 1/6 (16.7%) 4 2/3 (66.7%) 2 5/6 (83.3%) 16 0/1 (0%) 0 1/1 (100%) 6 10/45 (22.2%) 22 1/1 (100%) 1 4/10 (40%) 6
    Nausea 1/6 (16.7%) 1 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 1/1 (100%) 1 7/45 (15.6%) 13 0/1 (0%) 0 2/10 (20%) 4
    Vomiting 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 7/45 (15.6%) 12 0/1 (0%) 0 2/10 (20%) 3
    Aerophagia 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Abdominal distension 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Abdominal pain 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Abdominal wall haematoma 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Gastrointestinal pain 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Haematochezia 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Haemorrhoidal haemorrhage 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Oral pain 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 2 1/45 (2.2%) 2 0/1 (0%) 0 0/10 (0%) 0
    Paraesthesia oral 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Rectal haemorrhage 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 2 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Toothache 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    General disorders
    Asthenia 1/6 (16.7%) 4 1/3 (33.3%) 2 2/6 (33.3%) 4 1/1 (100%) 1 0/1 (0%) 0 8/45 (17.8%) 9 0/1 (0%) 0 3/10 (30%) 3
    Chest pain 0/6 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 3 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Face oedema 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Fatigue 1/6 (16.7%) 1 0/3 (0%) 0 3/6 (50%) 5 1/1 (100%) 1 1/1 (100%) 6 11/45 (24.4%) 29 0/1 (0%) 0 1/10 (10%) 1
    Oedema 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 6/45 (13.3%) 9 0/1 (0%) 0 0/10 (0%) 0
    Oedema peripheral 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 5 0/1 (0%) 0 1/1 (100%) 1 7/45 (15.6%) 12 0/1 (0%) 0 0/10 (0%) 0
    Pyrexia 1/6 (16.7%) 1 1/3 (33.3%) 3 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 6/45 (13.3%) 8 0/1 (0%) 0 4/10 (40%) 6
    Chills 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Mucosal inflammation 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 4 0/1 (0%) 0 1/1 (100%) 1 1/45 (2.2%) 2 0/1 (0%) 0 0/10 (0%) 0
    Non-cardiac chest pain 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 1/1 (100%) 1 0/10 (0%) 0
    Pain 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/1 (100%) 1 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Peripheral swelling 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Swelling face 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Injection site bruising 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 1/1 (100%) 1 0/10 (0%) 0
    Hepatobiliary disorders
    Hepatocellular injury 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Hypertransaminasaemia 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Cholelithiasis 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Hyperbilirubinaemia 1/6 (16.7%) 2 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Infections and infestations
    Bronchitis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 2/10 (20%) 3
    Gastroenteritis viral 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Nasopharyngitis 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Pneumonia 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 2 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 2/10 (20%) 3
    Respiratory tract infection 2/6 (33.3%) 2 1/3 (33.3%) 2 1/6 (16.7%) 3 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 7 0/1 (0%) 0 1/10 (10%) 1
    Rhinitis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 2/10 (20%) 2
    Tongue fungal infection 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Tooth infection 2/6 (33.3%) 2 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Upper respiratory tract infection 2/6 (33.3%) 11 0/3 (0%) 0 3/6 (50%) 3 0/1 (0%) 0 0/1 (0%) 0 6/45 (13.3%) 10 0/1 (0%) 0 1/10 (10%) 1
    Viral upper respiratory tract infection 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Candida infection 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Cystitis 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Corona virus infection 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Gastroenteritis 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Herpes zoster 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Infection 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Otitis media 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Viral infection 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Ear infection 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 1/1 (100%) 1 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Oesophageal candidiasis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Oral candidiasis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Pharyngitis 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Skin infection 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 1/1 (100%) 1 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Urinary tract infection 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 3 0/1 (0%) 0 0/10 (0%) 0
    Injury, poisoning and procedural complications
    Accidental overdose 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Contusion 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 1/1 (100%) 1 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Eye contusion 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Face injury 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Fall 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 3 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Lumbar vertebral fracture 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Skin abrasion 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 2 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Spinal fracture 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Tooth fracture 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 3 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Investigations
    Alanine aminotransferase increased 0/6 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 0/1 (0%) 0 5/45 (11.1%) 8 0/1 (0%) 0 1/10 (10%) 1
    Blood creatinine increased 1/6 (16.7%) 2 1/3 (33.3%) 1 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 6/45 (13.3%) 9 0/1 (0%) 0 2/10 (20%) 7
    Gamma-glutamyltransferase increased 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Platelet count decreased 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 1/10 (10%) 3
    Aspartate aminotransferase increased 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 0/10 (0%) 0
    Blood bilirubin increased 1/6 (16.7%) 5 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 5 0/1 (0%) 0 0/10 (0%) 0
    Blood urine present 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Lymphocyte count decreased 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 2 0/1 (0%) 0 0/10 (0%) 0
    Monocyte count increased 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Neutrophil count decreased 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 9 0/1 (0%) 0 0/10 (0%) 0
    Serum ferritin decreased 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Transaminases increased 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Metabolism and nutrition disorders
    Decreased appetite 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 0/10 (0%) 0
    Hyperglycaemia 2/6 (33.3%) 6 0/3 (0%) 0 2/6 (33.3%) 13 1/1 (100%) 2 0/1 (0%) 0 9/45 (20%) 15 0/1 (0%) 0 1/10 (10%) 1
    Hypokalaemia 1/6 (16.7%) 1 0/3 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0 0/1 (0%) 0 4/45 (8.9%) 5 0/1 (0%) 0 1/10 (10%) 1
    Hypomagnesaemia 1/6 (16.7%) 1 0/3 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0 1/1 (100%) 1 6/45 (13.3%) 7 1/1 (100%) 2 0/10 (0%) 0
    Hypercalcaemia 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Hyperuricaemia 2/6 (33.3%) 2 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Hypocalcaemia 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Hyponatraemia 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Hypophosphataemia 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 3 0/1 (0%) 0 0/10 (0%) 0
    Hypoproteinaemia 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 4 0/1 (0%) 0 0/10 (0%) 0
    Back pain 2/6 (33.3%) 2 1/3 (33.3%) 1 3/6 (50%) 4 1/1 (100%) 1 0/1 (0%) 0 4/45 (8.9%) 4 0/1 (0%) 0 1/10 (10%) 2
    Bone pain 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/1 (100%) 2 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Bone swelling 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Muscle spasms 0/6 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 5 1/1 (100%) 1 1/1 (100%) 1 8/45 (17.8%) 9 0/1 (0%) 0 3/10 (30%) 6
    Musculoskeletal chest pain 1/6 (16.7%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Myalgia 0/6 (0%) 0 0/3 (0%) 0 4/6 (66.7%) 10 0/1 (0%) 0 1/1 (100%) 1 7/45 (15.6%) 23 0/1 (0%) 0 0/10 (0%) 0
    Pain in extremity 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 2 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Muscular weakness 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Musculoskeletal discomfort 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Osteonecrosis of jaw 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Nervous system disorders
    Dizziness 0/6 (0%) 0 0/3 (0%) 0 3/6 (50%) 12 1/1 (100%) 1 1/1 (100%) 2 6/45 (13.3%) 20 1/1 (100%) 1 1/10 (10%) 1
    Headache 0/6 (0%) 0 0/3 (0%) 0 3/6 (50%) 3 0/1 (0%) 0 1/1 (100%) 2 5/45 (11.1%) 5 0/1 (0%) 0 3/10 (30%) 3
    Memory impairment 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/1 (100%) 3 2/45 (4.4%) 4 0/1 (0%) 0 0/10 (0%) 0
    Neuropathy peripheral 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 1/10 (10%) 1
    Peripheral sensory neuropathy 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 2 0/1 (0%) 0 0/1 (0%) 0 5/45 (11.1%) 10 0/1 (0%) 0 1/10 (10%) 1
    Sciatica 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Tremor 0/6 (0%) 0 1/3 (33.3%) 1 2/6 (33.3%) 2 0/1 (0%) 0 1/1 (100%) 2 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Cognitive disorder 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Disturbance in attention 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Mental impairment 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Paraesthesia 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Somnolence 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Psychiatric disorders
    Agitation 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 2
    Anxiety 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 0/10 (0%) 0
    Insomnia 0/6 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 2 0/1 (0%) 0 0/1 (0%) 0 7/45 (15.6%) 8 0/1 (0%) 0 2/10 (20%) 2
    Sleep disorder 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 1/10 (10%) 1
    Depression 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Confusional state 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 0/10 (0%) 0
    Renal and urinary disorders
    Acute kidney injury 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 2/10 (20%) 2
    Nephritis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Reproductive system and breast disorders
    Nipple pain 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Chronic obstructive pulmonary disease 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Cough 1/6 (16.7%) 1 0/3 (0%) 0 2/6 (33.3%) 4 1/1 (100%) 1 0/1 (0%) 0 10/45 (22.2%) 14 0/1 (0%) 0 0/10 (0%) 0
    Dysphonia 1/6 (16.7%) 1 1/3 (33.3%) 1 2/6 (33.3%) 2 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Dyspnoea 0/6 (0%) 0 1/3 (33.3%) 2 2/6 (33.3%) 7 0/1 (0%) 0 0/1 (0%) 0 14/45 (31.1%) 19 0/1 (0%) 0 0/10 (0%) 0
    Epistaxis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 3 3/45 (6.7%) 3 0/1 (0%) 0 0/10 (0%) 0
    Nasal congestion 0/6 (0%) 0 1/3 (33.3%) 1 1/6 (16.7%) 3 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 5 1/1 (100%) 1 0/10 (0%) 0
    Pharyngeal erythema 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Productive cough 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 2/45 (4.4%) 2 0/1 (0%) 0 1/10 (10%) 1
    Rhinorrhoea 1/6 (16.7%) 1 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 0/10 (0%) 0
    Hiccups 1/6 (16.7%) 1 1/3 (33.3%) 1 1/6 (16.7%) 6 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Lower respiratory tract congestion 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Lung infiltration 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Oropharyngeal pain 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 1/1 (100%) 1 1/45 (2.2%) 1 0/1 (0%) 0 0/10 (0%) 0
    Pleural effusion 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 1/1 (100%) 1 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Skin and subcutaneous tissue disorders
    Dry skin 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Ecchymosis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Pruritus 2/6 (33.3%) 2 0/3 (0%) 0 2/6 (33.3%) 4 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 4 1/1 (100%) 2 1/10 (10%) 1
    Rash 0/6 (0%) 0 0/3 (0%) 0 2/6 (33.3%) 8 0/1 (0%) 0 1/1 (100%) 2 4/45 (8.9%) 4 0/1 (0%) 0 2/10 (20%) 2
    Skin lesion 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Night sweats 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Skin fissures 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Hyperhidrosis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 3 0/1 (0%) 0 0/10 (0%) 0
    Vascular disorders
    Deep vein thrombosis 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 1/10 (10%) 1
    Haematoma 1/6 (16.7%) 1 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Hypotension 0/6 (0%) 0 1/3 (33.3%) 1 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Flushing 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 1/1 (100%) 1 2/45 (4.4%) 2 0/1 (0%) 0 0/10 (0%) 0
    Phlebitis 0/6 (0%) 0 0/3 (0%) 0 1/6 (16.7%) 1 0/1 (0%) 0 0/1 (0%) 0 0/45 (0%) 0 0/1 (0%) 0 0/10 (0%) 0
    Hypertension 0/6 (0%) 0 0/3 (0%) 0 0/6 (0%) 0 0/1 (0%) 0 0/1 (0%) 0 3/45 (6.7%) 5 0/1 (0%) 0 0/10 (0%) 0

    Limitations/Caveats

    Enrollment of participants into this study was stopped after the FDA implemented a clinical hold after determining the risks of pembrolizumab + pomalidomide or lenalidomide outweighed any potential benefit for participants with multiple myeloma.

    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:
    NCT02036502
    Other Study ID Numbers:
    • 3475-023
    • 2013-003512-44
    • MK-3475-023
    • KEYNOTE-023
    First Posted:
    Jan 15, 2014
    Last Update Posted:
    Apr 8, 2021
    Last Verified:
    Mar 1, 2021