Back to resultsStudy of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (MK-3475-183/KEYNOTE-183)
Primary Purpose
Multiple Myeloma
Status
Terminated
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Pembrolizumab
Pomalidomide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring PDL1, PD1, Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Has a confirmed diagnosis of active multiple myeloma and measurable disease
- Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and must have failed last line of treatment (refractory to last line of treatment)
- Prior anti-myeloma treatments must have included an immunomodulatory drug (IMiD) AND proteasome inhibitor alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor
- Has performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- Female participants of childbearing potential must have 2 negative urine human chorionic gonadotropin tests within 10 to 14 days and within 24 hours prior to receiving study medication
- Female participants of childbearing potential and male participants must agree to use adequate contraception 28 days prior to study start and continuing for up to 28 days after the last dose of pomalidomide (or 120 days after the last dose of pembrolizumab)
Exclusion Criteria:
- Has had prior anti-myeloma therapy within 2 weeks prior to study start and has not recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events due to a previously administered agent
- Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease [GVHD]).
- Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first infusion or is planning for or is eligible for auto-SCT
- Has received previous therapy with pomalidomide
- Has peripheral neuropathy ≥ Grade 2
- Has a known additional malignancy that is progressing or requires active treatment within the last 5 years (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy)
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
- Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways)
- Is pregnant or breast-feeding
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Pembrolizumab+Pomalidomide+Dexamethasone
Pomalidomide+Dexamethasone
Arm Description
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
Outcomes
Primary Outcome Measures
Progression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria
Progression free survival was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS was assessed by CAC blinded central review according to the IMWG criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was July 9, 2018.
Overall Survival (OS)
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Median overall survival was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was August 3, 2020.
Secondary Outcome Measures
Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
ORR was defined as the percentage of the participants in the analysis population who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]) according to the IMWG. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The database cutoff date was July 9, 2018.
Participants Experiencing One or More Adverse Events (AEs)
An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Database cutoff was August 3, 2020.
Participants Discontinuing Study Investigational Product Due to an AE
An adverse event was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Database cutoff was August 3, 2020.
Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
Disease control rate was the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, minimal response (MR) or have demonstrated stable disease (SD) for at least 12 weeks prior to any evidence of progression. PD was development of or an increase in the size of bone lesions or soft tissue plasmacytomas. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry/fluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018.
Second Progression Free Survival (PFS2)
PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. As a result of a full clinical hold by FDA that led to discontinuation of study enrollment, no data was collected for analysis of PFS2.
Full Information
NCT ID
NCT02576977
First Posted
October 14, 2015
Last Updated
September 13, 2021
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT02576977
Brief Title
Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (MK-3475-183/KEYNOTE-183)
Official Title
A Phase III Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (KEYNOTE 183)
Study Type
Interventional
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early due to business reasons
Study Start Date
October 19, 2015 (Actual)
Primary Completion Date
July 9, 2018 (Actual)
Study Completion Date
July 16, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare the efficacy of pomalidomide and low dose dexamethasone with pembrolizumab (MK-3475) to that of pomalidomide and low dose dexamethasone without pembrolizumab in terms of Progression-Free Survival (PFS) in participants with refractory or relapsed and refractory multiple myeloma (rrMM) who have undergone at least 2 lines of prior treatment. The study's 2 primary hypotheses are: 1. Pembrolizumab in combination with pomalidomide and low dose dexamethasone prolongs PFS as assessed by Clinical Adjudication Committee (CAC) blinded central review using International Myeloma Working Group Criteria for Response Assessment in Multiple Myeloma (IMWG) criteria compared to treatment with pomalidomide and low dose dexamethasone standard of care (SOC) alone. 2. Pembrolizumab in combination with pomalidomide and low dose dexamethasone prolongs OS compared to treatment with pomalidomide and low dose dexamethasone (SOC) alone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
PDL1, PD1, Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
251 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Pembrolizumab+Pomalidomide+Dexamethasone
Arm Type
Experimental
Arm Description
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
Arm Title
Pomalidomide+Dexamethasone
Arm Type
Active Comparator
Arm Description
Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.
Intervention Type
Biological
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
KEYTRUDA®, MK-3475, SCH 9000475
Intervention Description
pembrolizumab 200 mg IV infusion
Intervention Type
Drug
Intervention Name(s)
Pomalidomide
Other Intervention Name(s)
POMALYST®
Intervention Description
pomalidomide 4 mg capsules
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
dexamethasone 40 mg tablets
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) Assessed by Clinical Adjudication Committee (CAC) Blinded Central Review According to the International Myeloma Working Group (IMWG) Response Criteria
Description
Progression free survival was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS was assessed by CAC blinded central review according to the IMWG criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was July 9, 2018.
Time Frame
Up to approximately 30 months
Title
Overall Survival (OS)
Description
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Median overall survival was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was August 3, 2020.
Time Frame
Up to approximately 54 months
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
Description
ORR was defined as the percentage of the participants in the analysis population who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]) according to the IMWG. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The database cutoff date was July 9, 2018.
Time Frame
Up to approximately 30 months
Title
Participants Experiencing One or More Adverse Events (AEs)
Description
An adverse event (AE) was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Database cutoff was August 3, 2020.
Time Frame
Up to approximately 54 months
Title
Participants Discontinuing Study Investigational Product Due to an AE
Description
An adverse event was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. Database cutoff was August 3, 2020.
Time Frame
Up to approximately 54 months
Title
Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
Description
Disease control rate was the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, minimal response (MR) or have demonstrated stable disease (SD) for at least 12 weeks prior to any evidence of progression. PD was development of or an increase in the size of bone lesions or soft tissue plasmacytomas. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry/fluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018.
Time Frame
Up to approximately 30 months
Title
Second Progression Free Survival (PFS2)
Description
PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. As a result of a full clinical hold by FDA that led to discontinuation of study enrollment, no data was collected for analysis of PFS2.
Time Frame
Up to approximately 30 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Has a confirmed diagnosis of active multiple myeloma and measurable disease
Must have undergone prior treatment with ≥2 treatment lines of anti-myeloma therapy and must have failed last line of treatment (refractory to last line of treatment)
Prior anti-myeloma treatments must have included an immunomodulatory drug (IMiD) AND proteasome inhibitor alone or in combination and participant must have failed therapy with an IMiD OR proteasome inhibitor
Has performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
Female participants of childbearing potential must have 2 negative urine human chorionic gonadotropin tests within 10 to 14 days and within 24 hours prior to receiving study medication
Female participants of childbearing potential and male participants must agree to use adequate contraception 28 days prior to study start and continuing for up to 28 days after the last dose of pomalidomide (or 120 days after the last dose of pembrolizumab)
Exclusion Criteria:
Has had prior anti-myeloma therapy within 2 weeks prior to study start and has not recovered (i.e., ≤ Grade 1 or at Baseline) from adverse events due to a previously administered agent
Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Participants who have had a transplant greater than 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease [GVHD]).
Has received autologous stem cell transplant (auto-SCT) within 12 weeks before the first infusion or is planning for or is eligible for auto-SCT
Has received previous therapy with pomalidomide
Has peripheral neuropathy ≥ Grade 2
Has a known additional malignancy that is progressing or requires active treatment within the last 5 years (except for basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy)
Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
Has received prior therapy with an anti-programmed cell death 1 receptor (anti-PD-1), antiprogrammed death-ligand 1 (anti-PD-L1), anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways)
Is pregnant or breast-feeding
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
33086159
Citation
Liao JJZ, Farooqui MZH, Marinello P, Hartzel J, Anderson K, Ma J, Gause CK. Using artificial intelligence tools in answering important clinical questions: The KEYNOTE-183 multiple myeloma experience. Contemp Clin Trials. 2020 Dec;99:106179. doi: 10.1016/j.cct.2020.106179. Epub 2020 Oct 18.
Results Reference
derived
PubMed Identifier
31327687
Citation
Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, Goldschmidt H, Larocca A, Chanan-Khan A, Sherbenou D, Avivi I, Benyamini N, Iida S, Matsumoto M, Suzuki K, Ribrag V, Usmani SZ, Jagannath S, Ocio EM, Rodriguez-Otero P, San Miguel J, Kher U, Farooqui M, Liao J, Marinello P, Lonial S; KEYNOTE-183 Investigators. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019 Sep;6(9):e459-e469. doi: 10.1016/S2352-3026(19)30110-3. Epub 2019 Jul 18.
Results Reference
derived
Links:
URL
http://merckoncologyclinicaltrials.com
Description
Merck Oncology Clinical Trials Information
Learn more about this trial
Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab (MK-3475) in Refractory or Relapsed and Refractory Multiple Myeloma (rrMM) (MK-3475-183/KEYNOTE-183)
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