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

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

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Biological: Pembrolizumab; Drug: Pomalidomide; Drug: Dexamethasone	Phase 3

Study Design

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

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab+Pomalidomide+Dexamethasone Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 every 3 weeks (Q3W) PLUS pomalidomide 4 mg orally (PO) on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.	Biological: Pembrolizumab; pembrolizumab 200 mg IV infusion; Other Names: KEYTRUDA® MK-3475 SCH 9000475 ; Drug: Pomalidomide; pomalidomide 4 mg capsules; Other Names: POMALYST® ; Drug: Dexamethasone; dexamethasone 40 mg tablets
Active Comparator: Pomalidomide+Dexamethasone Participants receive pomalidomide 4 mg PO on Days 1 to 21 of each 28-day cycle PLUS dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle.	Drug: Pomalidomide; pomalidomide 4 mg capsules; Other Names: POMALYST® ; Drug: Dexamethasone; dexamethasone 40 mg tablets

Outcome Measures

Primary Outcome Measures

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

   Progression free survival was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. PFS was assessed by CAC blinded central review according to the IMWG criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. The database cutoff date was July 9, 2018.

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

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

Secondary Outcome Measures

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

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

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

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

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

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

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

   Disease control rate was the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, minimal response (MR) or have demonstrated stable disease (SD) for at least 12 weeks prior to any evidence of progression. PD was development of or an increase in the size of bone lesions or soft tissue plasmacytomas. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum FLC assay ratio and absence of clonal cells in bone marrow by immunohistochemistry/fluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018.

5. Second Progression Free Survival (PFS2) [Up to approximately 30 months]

   PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. As a result of a full clinical hold by FDA that led to discontinuation of study enrollment, no data was collected for analysis of PFS2.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has a confirmed diagnosis of active multiple myeloma and measurable disease

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

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

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

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

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

Exclusion Criteria:

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

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

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

• Has received previous therapy with pomalidomide

• Has peripheral neuropathy ≥ Grade 2

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

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

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

• Is pregnant or breast-feeding

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 4, 2020

More Information

Additional Information:

• Merck Oncology Clinical Trials Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02576977
• Other Study ID Numbers: 3475-183; 2015-002509-13; 163146; MK-3475-183; KEYNOTE-183
• First Posted: Oct 15, 2015
• Last Update Posted: Oct 8, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck Sharp & Dohme LLC: PDL1; PD1; Multiple Myeloma
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Pembrolizumab; Pomalidomide

Study Results

Participant Flow

Recruitment Details	Subject Disposition as per database cutoff date of August 3, 2020.
Pre-assignment Detail	Note: For administrative reasons (a noncompliant site), one participant in the SOC arm was recorded as "Ongoing in Trial" in the CSR Disposition Table and "Final Disposition Unknown" here.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Period Title: Overall Study
STARTED	126	125
Treated	122	123
COMPLETED	0	0
NOT COMPLETED	126	125

Baseline Characteristics

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone	Total
Arm/Group 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.	Total of all reporting groups
Overall Participants	126	125	251
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	65.5 (9.3)	66.4 (10.0)	65.9 (9.6)
Sex: Female, Male (Count of Participants)
Female	48 38.1%	46 36.8%	94 37.5%
Male	78 61.9%	79 63.2%	157 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	8 6.3%	5 4%	13 5.2%
Not Hispanic or Latino	110 87.3%	117 93.6%	227 90.4%
Unknown or Not Reported	8 6.3%	3 2.4%	11 4.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	17 13.5%	12 9.6%	29 11.6%
Native Hawaiian or Other Pacific Islander	2 1.6%	1 0.8%	3 1.2%
Black or African American	10 7.9%	14 11.2%	24 9.6%
White	92 73%	95 76%	187 74.5%
More than one race	1 0.8%	2 1.6%	3 1.2%
Unknown or Not Reported	4 3.2%	1 0.8%	5 2%
Disease Status (Refractory vs. Sensitive to Lenalidomide) (Count of Participants)
Refractory to Lenalidomide	108 85.7%	108 86.4%	216 86.1%
Sensitive to Lenalidomide	18 14.3%	17 13.6%	35 13.9%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Measure Participants	126	125
Median (95% Confidence Interval) [Months]	5.7	7.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab+Pomalidomide+Dexamethasone, Standard of Care (SOC) Pomalidomide+Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99324
	Comments
	Method	Log Rank
	Comments	One-sided p-value based on Stratified log-rank test.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 1.08 to 2.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by disease status (refractory vs. sensitive to Lenalidomide) and Lines of previous treatments (two vs. three or more).

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Measure Participants	126	125
Median (95% Confidence Interval) [Months]	21.0	39.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab+Pomalidomide+Dexamethasone, Standard of Care (SOC) Pomalidomide+Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.99989
	Comments
	Method	Log Rank
	Comments	One-sided p-value based on Stratified log-rank test.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.84
	Confidence Interval	(2-Sided) 95%; 1.32 to 2.55
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		The Hazard Ratio and 95% confidence intervals were based on Cox regression model with treatment as a covariate stratified by disease status (refractory vs. sensitive to Lenalidomide) and Lines of previous treatments (two vs. three or more).

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Measure Participants	126	125
Number (95% Confidence Interval) [Percentage of participants]	37.3 29.6%	42.4 33.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab+Pomalidomide+Dexamethasone, Standard of Care (SOC) Pomalidomide+Dexamethasone
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.79921
	Comments
	Method	Miettinen & Nurminen method
	Comments
Method of Estimation	Estimation Parameter	Difference in % vs. SOC
	Estimated Value	-5.2
	Confidence Interval	(2-Sided) 95%; -17.1 to 6.9
	Parameter Dispersion	Type: Value:
	Estimation Comments
Other Statistical Analysis		Based on Miettinen & Nurminen method stratified by disease status (refractory vs. sensitive to Lenalidomide) and Lines of previous treatments (two vs. three or more); If there were no participants in one of the treatment groups involved in a comparison for a particular stratum, then that stratum was excluded from the treatment comparison.

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Measure Participants	122	123
Count of Participants [Participants]	122 96.8%	119 95.2%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants who received at least one dose of study treatment. Participants were included in the treatment group corresponding to the study treatment they actually received.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Measure Participants	122	123
Count of Participants [Participants]	26 20.6%	10 8%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Measure Participants	126	125
Number (95% Confidence Interval) [Percentage of participants]	88.1 69.9%	84.8 67.8%

7. Secondary Outcome

Title	Second Progression Free Survival (PFS2)
Description	PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. 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

Outcome Measure Data

Analysis Population Description

The analysis population was to include all randomized participants. Study treatment was terminated early and no data was collected for analysis of PFS2.

Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone	Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
Measure Participants	0	0

Adverse Events

Time Frame	Up to approximately 54 months
Adverse Event Reporting Description	The analysis population for all-cause mortality was all randomized participants and for adverse events was the treated participants. Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered related to study treatment, therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as AEs. The database cutoff date was August 3, 2020.
Arm/Group Title	Pembrolizumab+Pomalidomide+Dexamethasone		Standard of Care (SOC) Pomalidomide+Dexamethasone
Arm/Group 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.
All Cause Mortality
	Pembrolizumab+Pomalidomide+Dexamethasone		Standard of Care (SOC) Pomalidomide+Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	86/126 (68.3%)		64/125 (51.2%)
Serious Adverse Events
	Pembrolizumab+Pomalidomide+Dexamethasone		Standard of Care (SOC) Pomalidomide+Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/122 (64.8%)		57/123 (46.3%)
Blood and lymphatic system disorders
Anaemia	1/122 (0.8%)	1	4/123 (3.3%)	4
Anaemia of malignant disease	0/122 (0%)	0	1/123 (0.8%)	1
Disseminated intravascular coagulation	1/122 (0.8%)	1	0/123 (0%)	0
Febrile bone marrow aplasia	1/122 (0.8%)	1	0/123 (0%)	0
Febrile neutropenia	4/122 (3.3%)	4	4/123 (3.3%)	5
Pancytopenia	0/122 (0%)	0	1/123 (0.8%)	1
Thrombocytopenia	0/122 (0%)	0	1/123 (0.8%)	1
Cardiac disorders
Atrial fibrillation	2/122 (1.6%)	2	1/123 (0.8%)	1
Cardiac failure	1/122 (0.8%)	1	1/123 (0.8%)	1
Cardiogenic shock	1/122 (0.8%)	1	0/123 (0%)	0
Myocardial infarction	2/122 (1.6%)	2	0/123 (0%)	0
Myocarditis	1/122 (0.8%)	2	0/123 (0%)	0
Pericardial haemorrhage	1/122 (0.8%)	1	0/123 (0%)	0
Supraventricular tachycardia	1/122 (0.8%)	1	0/123 (0%)	0
Ear and labyrinth disorders
Vertigo	1/122 (0.8%)	1	0/123 (0%)	0
Vertigo positional	1/122 (0.8%)	1	0/123 (0%)	0
Endocrine disorders
Adrenal insufficiency	1/122 (0.8%)	1	0/123 (0%)	0
Eye disorders
Cataract	0/122 (0%)	0	1/123 (0.8%)	1
Gastrointestinal disorders
Constipation	1/122 (0.8%)	1	0/123 (0%)	0
Diarrhoea	1/122 (0.8%)	1	1/123 (0.8%)	1
Ileus	1/122 (0.8%)	1	0/123 (0%)	0
Inguinal hernia	1/122 (0.8%)	1	0/123 (0%)	0
Large intestine perforation	1/122 (0.8%)	1	0/123 (0%)	0
Tooth disorder	1/122 (0.8%)	1	0/123 (0%)	0
Upper gastrointestinal haemorrhage	0/122 (0%)	0	1/123 (0.8%)	1
General disorders
Chest pain	1/122 (0.8%)	1	0/123 (0%)	0
Death	3/122 (2.5%)	3	0/123 (0%)	0
Fatigue	0/122 (0%)	0	2/123 (1.6%)	2
Oedema peripheral	0/122 (0%)	0	1/123 (0.8%)	1
Pain	0/122 (0%)	0	1/123 (0.8%)	1
Pyrexia	3/122 (2.5%)	3	5/123 (4.1%)	5
Hepatobiliary disorders
Hepatitis	1/122 (0.8%)	1	0/123 (0%)	0
Infections and infestations
Anal abscess	0/122 (0%)	0	1/123 (0.8%)	1
Arthritis bacterial	1/122 (0.8%)	1	0/123 (0%)	0
Bacteraemia	1/122 (0.8%)	1	0/123 (0%)	0
Bacterial infection	1/122 (0.8%)	1	0/123 (0%)	0
Bacterial sepsis	1/122 (0.8%)	1	0/123 (0%)	0
Bronchitis	1/122 (0.8%)	1	1/123 (0.8%)	1
Bronchitis bacterial	0/122 (0%)	0	1/123 (0.8%)	1
Cellulitis	2/122 (1.6%)	2	0/123 (0%)	0
Clostridium difficile colitis	0/122 (0%)	0	1/123 (0.8%)	1
Clostridium difficile infection	1/122 (0.8%)	1	0/123 (0%)	0
Escherichia bacteraemia	0/122 (0%)	0	1/123 (0.8%)	1
Genital herpes simplex	0/122 (0%)	0	1/123 (0.8%)	1
Infective exacerbation of chronic obstructive airways disease	1/122 (0.8%)	4	0/123 (0%)	0
Influenza	1/122 (0.8%)	1	3/123 (2.4%)	3
Lower respiratory tract infection	1/122 (0.8%)	1	0/123 (0%)	0
Neutropenic sepsis	2/122 (1.6%)	2	0/123 (0%)	0
Parainfluenzae virus infection	1/122 (0.8%)	1	0/123 (0%)	0
Parotitis	1/122 (0.8%)	1	0/123 (0%)	0
Pneumocystis jirovecii pneumonia	3/122 (2.5%)	3	0/123 (0%)	0
Pneumonia	23/122 (18.9%)	29	17/123 (13.8%)	21
Pneumonia bacterial	1/122 (0.8%)	1	0/123 (0%)	0
Pneumonia influenzal	0/122 (0%)	0	1/123 (0.8%)	1
Pneumonia parainfluenzae viral	1/122 (0.8%)	1	0/123 (0%)	0
Pulmonary sepsis	1/122 (0.8%)	1	0/123 (0%)	0
Respiratory tract infection	1/122 (0.8%)	1	1/123 (0.8%)	1
Respiratory tract infection viral	1/122 (0.8%)	1	0/123 (0%)	0
Rhinovirus infection	1/122 (0.8%)	1	0/123 (0%)	0
Sepsis	3/122 (2.5%)	3	3/123 (2.4%)	3
Septic shock	2/122 (1.6%)	2	1/123 (0.8%)	1
Sinusitis	1/122 (0.8%)	1	1/123 (0.8%)	1
Subcutaneous abscess	0/122 (0%)	0	1/123 (0.8%)	1
Upper respiratory tract infection	1/122 (0.8%)	1	3/123 (2.4%)	3
Urinary tract infection	1/122 (0.8%)	1	1/123 (0.8%)	1
Viral infection	1/122 (0.8%)	1	0/123 (0%)	0
Wound infection	1/122 (0.8%)	1	0/123 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	0/122 (0%)	0	1/123 (0.8%)	1
Femoral neck fracture	0/122 (0%)	0	1/123 (0.8%)	1
Femur fracture	1/122 (0.8%)	2	0/123 (0%)	0
Fibula fracture	1/122 (0.8%)	1	0/123 (0%)	0
Hip fracture	1/122 (0.8%)	1	0/123 (0%)	0
Infusion related reaction	1/122 (0.8%)	1	0/123 (0%)	0
Muscle strain	1/122 (0.8%)	1	0/123 (0%)	0
Post procedural fever	1/122 (0.8%)	1	0/123 (0%)	0
Subdural haematoma	1/122 (0.8%)	1	0/123 (0%)	0
Upper limb fracture	0/122 (0%)	0	1/123 (0.8%)	1
Investigations
Alanine aminotransferase increased	1/122 (0.8%)	1	0/123 (0%)	0
Aspartate aminotransferase increased	1/122 (0.8%)	1	0/123 (0%)	0
Neutrophil count decreased	2/122 (1.6%)	2	0/123 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/122 (0%)	0	2/123 (1.6%)	2
Gout	0/122 (0%)	0	1/123 (0.8%)	2
Hypercalcaemia	2/122 (1.6%)	3	1/123 (0.8%)	1
Hypokalaemia	1/122 (0.8%)	1	1/123 (0.8%)	1
Hyponatraemia	1/122 (0.8%)	1	0/123 (0%)	0
Hypovolaemia	0/122 (0%)	0	1/123 (0.8%)	1
Steroid diabetes	0/122 (0%)	0	1/123 (0.8%)	1
Musculoskeletal and connective tissue disorders
Fracture pain	0/122 (0%)	0	1/123 (0.8%)	1
Muscular weakness	1/122 (0.8%)	1	0/123 (0%)	0
Osteonecrosis of jaw	1/122 (0.8%)	1	0/123 (0%)	0
Pathological fracture	1/122 (0.8%)	1	3/123 (2.4%)	4
Polyarthritis	1/122 (0.8%)	1	0/123 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/122 (0.8%)	2	1/123 (0.8%)	1
Basosquamous carcinoma of skin	1/122 (0.8%)	1	0/123 (0%)	0
Colorectal adenocarcinoma	1/122 (0.8%)	1	0/123 (0%)	0
Intestinal adenocarcinoma	1/122 (0.8%)	1	0/123 (0%)	0
Malignant ascites	1/122 (0.8%)	1	0/123 (0%)	0
Squamous cell carcinoma	2/122 (1.6%)	2	1/123 (0.8%)	1
Squamous cell carcinoma of skin	1/122 (0.8%)	1	0/123 (0%)	0
Nervous system disorders
Balance disorder	1/122 (0.8%)	1	0/123 (0%)	0
Central nervous system lesion	0/122 (0%)	0	1/123 (0.8%)	1
Cerebral haemorrhage	1/122 (0.8%)	1	0/123 (0%)	0
Cerebrovascular accident	2/122 (1.6%)	2	1/123 (0.8%)	1
Cognitive disorder	0/122 (0%)	0	1/123 (0.8%)	1
IIIrd nerve disorder	1/122 (0.8%)	1	0/123 (0%)	0
Seizure	0/122 (0%)	0	1/123 (0.8%)	1
Somnolence	0/122 (0%)	0	1/123 (0.8%)	1
Syncope	1/122 (0.8%)	1	0/123 (0%)	0
Psychiatric disorders
Delirium	0/122 (0%)	0	1/123 (0.8%)	1
Renal and urinary disorders
Acute kidney injury	4/122 (3.3%)	4	4/123 (3.3%)	4
Chronic kidney disease	1/122 (0.8%)	1	0/123 (0%)	0
Cystitis haemorrhagic	0/122 (0%)	0	1/123 (0.8%)	1
Renal failure	2/122 (1.6%)	2	2/123 (1.6%)	2
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/122 (0.8%)	1	0/123 (0%)	0
Acute respiratory failure	1/122 (0.8%)	1	1/123 (0.8%)	1
Asthma	1/122 (0.8%)	1	0/123 (0%)	0
Chronic obstructive pulmonary disease	2/122 (1.6%)	2	0/123 (0%)	0
Cough	0/122 (0%)	0	1/123 (0.8%)	1
Dyspnoea	1/122 (0.8%)	1	2/123 (1.6%)	2
Haemoptysis	0/122 (0%)	0	1/123 (0.8%)	1
Hypoxia	1/122 (0.8%)	1	1/123 (0.8%)	1
Interstitial lung disease	1/122 (0.8%)	1	0/123 (0%)	0
Pleural effusion	1/122 (0.8%)	1	0/123 (0%)	0
Pneumonitis	5/122 (4.1%)	5	0/123 (0%)	0
Pulmonary congestion	0/122 (0%)	0	1/123 (0.8%)	1
Pulmonary embolism	0/122 (0%)	0	4/123 (3.3%)	4
Pulmonary haemorrhage	1/122 (0.8%)	1	0/123 (0%)	0
Skin and subcutaneous tissue disorders
Panniculitis	1/122 (0.8%)	1	0/123 (0%)	0
Rash	0/122 (0%)	0	1/123 (0.8%)	1
Stevens-Johnson syndrome	1/122 (0.8%)	1	0/123 (0%)	0
Vascular disorders
Aortic stenosis	0/122 (0%)	0	1/123 (0.8%)	1
Deep vein thrombosis	0/122 (0%)	0	1/123 (0.8%)	1
Hypotension	1/122 (0.8%)	1	1/123 (0.8%)	1
Orthostatic hypotension	0/122 (0%)	0	1/123 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Pembrolizumab+Pomalidomide+Dexamethasone		Standard of Care (SOC) Pomalidomide+Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	115/122 (94.3%)		114/123 (92.7%)
Blood and lymphatic system disorders
Anaemia	34/122 (27.9%)	53	40/123 (32.5%)	57
Leukopenia	10/122 (8.2%)	21	9/123 (7.3%)	16
Neutropenia	49/122 (40.2%)	120	33/123 (26.8%)	63
Thrombocytopenia	26/122 (21.3%)	49	19/123 (15.4%)	27
Gastrointestinal disorders
Constipation	30/122 (24.6%)	37	26/123 (21.1%)	27
Diarrhoea	21/122 (17.2%)	30	27/123 (22%)	35
Gastrooesophageal reflux disease	4/122 (3.3%)	4	7/123 (5.7%)	7
Nausea	23/122 (18.9%)	26	16/123 (13%)	19
Vomiting	10/122 (8.2%)	17	13/123 (10.6%)	14
General disorders
Asthenia	15/122 (12.3%)	21	14/123 (11.4%)	17
Chest pain	9/122 (7.4%)	11	5/123 (4.1%)	6
Fatigue	33/122 (27%)	36	37/123 (30.1%)	44
Oedema peripheral	22/122 (18%)	25	20/123 (16.3%)	23
Pyrexia	26/122 (21.3%)	35	19/123 (15.4%)	23
Infections and infestations
Nasopharyngitis	7/122 (5.7%)	7	6/123 (4.9%)	8
Pneumonia	7/122 (5.7%)	7	2/123 (1.6%)	2
Upper respiratory tract infection	21/122 (17.2%)	27	25/123 (20.3%)	33
Urinary tract infection	1/122 (0.8%)	1	8/123 (6.5%)	9
Investigations
Alanine aminotransferase increased	10/122 (8.2%)	11	4/123 (3.3%)	4
Blood creatinine increased	7/122 (5.7%)	10	4/123 (3.3%)	4
Neutrophil count decreased	16/122 (13.1%)	28	17/123 (13.8%)	26
Platelet count decreased	7/122 (5.7%)	11	10/123 (8.1%)	12
Weight decreased	7/122 (5.7%)	7	5/123 (4.1%)	5
White blood cell count decreased	13/122 (10.7%)	19	11/123 (8.9%)	21
Metabolism and nutrition disorders
Decreased appetite	9/122 (7.4%)	9	8/123 (6.5%)	8
Hyperglycaemia	7/122 (5.7%)	7	5/123 (4.1%)	5
Hypokalaemia	11/122 (9%)	16	8/123 (6.5%)	9
Hypomagnesaemia	3/122 (2.5%)	6	8/123 (6.5%)	8
Musculoskeletal and connective tissue disorders
Arthralgia	10/122 (8.2%)	11	16/123 (13%)	17
Back pain	14/122 (11.5%)	15	21/123 (17.1%)	23
Muscle spasms	15/122 (12.3%)	16	14/123 (11.4%)	15
Muscular weakness	6/122 (4.9%)	10	11/123 (8.9%)	13
Musculoskeletal chest pain	12/122 (9.8%)	14	6/123 (4.9%)	6
Pain in extremity	6/122 (4.9%)	8	7/123 (5.7%)	7
Nervous system disorders
Dizziness	16/122 (13.1%)	19	14/123 (11.4%)	15
Headache	16/122 (13.1%)	20	5/123 (4.1%)	7
Neuropathy peripheral	8/122 (6.6%)	8	5/123 (4.1%)	5
Tremor	10/122 (8.2%)	11	10/123 (8.1%)	10
Psychiatric disorders
Depression	7/122 (5.7%)	7	3/123 (2.4%)	3
Insomnia	10/122 (8.2%)	11	17/123 (13.8%)	18
Respiratory, thoracic and mediastinal disorders
Cough	19/122 (15.6%)	23	18/123 (14.6%)	21
Dyspnoea	21/122 (17.2%)	26	19/123 (15.4%)	25
Epistaxis	9/122 (7.4%)	9	3/123 (2.4%)	5
Skin and subcutaneous tissue disorders
Pruritus	6/122 (4.9%)	6	10/123 (8.1%)	10
Rash	12/122 (9.8%)	13	10/123 (8.1%)	12

Limitations/Caveats

The MK-3475-183 study was stopped/terminated early. Endpoint statistics may be biased due to the incomplete treatment and follow-up of participants after study termination

More Information

Certain Agreements

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

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