Trial Outcomes & Findings for Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185) (NCT NCT02579863)

Last Updated: 2021-07-20

Results Overview

PFS was defined as the time from randomization to the first documented disease progression (events of new bone lesions, soft tissue plasmacytomas or an increase in existing lesions, or death due to any cause). The median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. Due to the small number of events, the tail of the estimated survival distribution was close to the median for both arms. The higher variability of the tail estimates resulted in observing the median estimate in the experimental arm but not in the standard of care arm even when number of events in 2 arms were similar. The database cutoff date was July 9, 2018.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

310 participants

Primary outcome timeframe

Up to approximately 30 months

Results posted on

2021-07-20

Participant Flow

This study was conducted at 140 centers in 15 countries. The database cutoff date was August 3, 2020.

Note: Due to administrative reasons (a noncompliant site), 2 participants in the Pembrolizumab plus SOC arm and one participant in the SOC arm, were recorded as "Ongoing in Trial" in the CSR Disposition Table and "Final Disposition Unknown" here.

Participant milestones

Participant milestones
Measure	Pembrolizumab + Lenalidomide + Dexamethasone Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Study STARTED	156	154
Overall Study Treated	154	148
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	156	154

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab + Lenalidomide + Dexamethasone Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Study Final Disposition Unknown	2	1
Overall Study Adverse Event	18	11
Overall Study Death	31	29
Overall Study Lost to Follow-up	2	1
Overall Study Physician Decision	1	2
Overall Study Screen Failure	0	2
Overall Study Study Terminated at Selected Sites	82	88
Overall Study Withdrawal by Subject	20	20

Baseline Characteristics

Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=156 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=154 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Total n=310 Participants Total of all reporting groups
Age, Continuous	74.4 Years STANDARD_DEVIATION 6.0 • n=5 Participants	74.3 Years STANDARD_DEVIATION 5.9 • n=7 Participants	74.3 Years STANDARD_DEVIATION 6.0 • n=5 Participants
Sex: Female, Male Female	85 Participants n=5 Participants	81 Participants n=7 Participants	166 Participants n=5 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	73 Participants n=7 Participants	144 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	143 Participants n=5 Participants	136 Participants n=7 Participants	279 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=5 Participants	14 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	27 Participants n=5 Participants	27 Participants n=7 Participants	54 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	3 Participants n=7 Participants	12 Participants n=5 Participants
Race (NIH/OMB) White	115 Participants n=5 Participants	121 Participants n=7 Participants	236 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
International Stage (I, II, III). Stage I	39 Participants n=5 Participants	53 Participants n=7 Participants	92 Participants n=5 Participants
International Stage (I, II, III). Stage II	70 Participants n=5 Participants	66 Participants n=7 Participants	136 Participants n=5 Participants
International Stage (I, II, III). Stage III	46 Participants n=5 Participants	34 Participants n=7 Participants	80 Participants n=5 Participants
International Stage (I, II, III). Missing	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 30 months

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

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=156 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=154 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review	19.6 Months Interval 15.3 to Upper Limit could not be estimated due to an insufficient number of events by the date of data cutoff.	NA Months Interval 15.5 to The Median was not reached, and the Upper Limit could not be estimated due to insufficient number of events by the date of data cutoff.

SECONDARY outcome

Timeframe: Up to approximately 55 months

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

OS was defined as the time from randomization to death due to any cause. OS was calculated from the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. This is an event-driven (events of death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). The database cutoff date was August 3, 2020.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=156 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=154 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Survival (OS)	NA Months Interval 44.6 to The Median was not reached, and the Upper Limit could not be estimated due to insufficient number of events before the date of data cutoff.	NA Months The Median was not reached, and the Upper and Lower Limits could not be estimated due to insufficient number of events before the date of data cutoff.

SECONDARY outcome

Timeframe: Up to approximately 30 months

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

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

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=156 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=154 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review	74.4 Percentage of participants Interval 66.8 to 81.0	68.8 Percentage of participants Interval 60.9 to 76.0

SECONDARY outcome

Timeframe: Up to approximately 30 months

Population: The analysis population included all randomized participants who demonstrated at least a partial response. Participants were included in the treatment group to which they were randomized.

Response duration was defined as the time from first documented evidence of at least a partial response (sCR+CR+VGPR+PR\]), until confirmed disease progression or death. DOR was calculated from product-limit (Kaplan-Meier) method for censored data. This is an event-driven (events of disease progression and death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). Full Range is the minimum and maximum of the observed duration of response. The data cutoff date was July 9, 2018.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=116 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=106 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review	NA Months The Median was not reached, and the limits could not be estimated due to the lack of progressive disease by the time of last disease assessment.	NA Months The Median was not reached, and the limits could not be estimated due to the lack of progressive disease by the time of last disease assessment.

SECONDARY outcome

Timeframe: Up to approximately 30 months

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

Disease control rate was defined as the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, or have demonstrated SD for at least 12 weeks prior to any evidence of progression. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND \<5% plasmacytomas in the bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component \<100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 hours; SD = not meeting the criteria for CR, VGPR, PR, or PD; PD = development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Data cutoff date was July 9, 2018.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=156 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=154 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review	89.1 Percentage of participants Interval 83.1 to 93.5	91.6 Percentage of participants Interval 86.0 to 95.4

SECONDARY outcome

Timeframe: Up to approximately 55 months

Population: The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized. PFS2 was not completed due to incomplete enrollment for a clinical hold and study cancellation.

PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. PFS was assessed by Clinical Adjudication Committee (CAC) blinded central review according to the IMWG response criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. PFS2 was not completed due to incomplete enrollment for a clinical hold and study cancellation.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to approximately 55 months

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

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

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=154 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=148 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Number of Participants Who Experienced One or More Adverse Events (AEs)	152 Participants	141 Participants

SECONDARY outcome

Timeframe: Up to approximately 55 months

Population: The analysis population consisted of all randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenalidomide + Dexamethasone n=154 Participants Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Lenolidomide + Dexamethasone n=148 Participants Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Number of Participants Discontinuing Study Treatment Due to an AE	44 Participants	26 Participants

Adverse Events

Pembrolizumab + Lenalidomide + Dexamethasone

Serious events: 91 serious events

Other events: 143 other events

Deaths: 51 deaths

Lenolidomide + Dexamethasone

Serious events: 65 serious events

Other events: 129 other events

Deaths: 43 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER