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NCT02579863

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)

Terminated Phase 3 Results posted Last updated 20 July 2021
What this trial tests

Phase 3 trial testing Pembrolizumab in Multiple Myeloma in 310 participants. Terminated before completion.

Timeline
19 October 2015
Primary endpoint
9 July 2018
13 July 2020

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 3
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment310
Start date19 October 2015
Primary completion9 July 2018
Estimated completion13 July 2020

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review Primary · Up to approximately 30 months

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

GroupValue95% CI
Pembrolizumab + Lenalidomide + Dexamethasone19.615.3 – NA
Lenolidomide + DexamethasoneNA15.5 – NA
Overall Survival (OS) Secondary · Up to approximately 55 months

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.

GroupValue95% CI
Pembrolizumab + Lenalidomide + DexamethasoneNA44.6 – NA
Lenolidomide + DexamethasoneNANA – NA
Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review Secondary · Up to approximately 30 months

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 immu

GroupValue95% CI
Pembrolizumab + Lenalidomide + Dexamethasone74.466.8 – 81.0
Lenolidomide + Dexamethasone68.860.9 – 76.0
Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review Secondary · Up to approximately 30 months

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.

GroupValue95% CI
Pembrolizumab + Lenalidomide + DexamethasoneNANA – NA
Lenolidomide + DexamethasoneNANA – NA
Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review Secondary · Up to approximately 30 months

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

GroupValue95% CI
Pembrolizumab + Lenalidomide + Dexamethasone89.183.1 – 93.5
Lenolidomide + Dexamethasone91.686.0 – 95.4
Number of Participants Who Experienced One or More Adverse Events (AEs) Secondary · Up to approximately 55 months

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.

GroupValue95% CI
Pembrolizumab + Lenalidomide + Dexamethasone152
Lenolidomide + Dexamethasone141
Number of Participants Discontinuing Study Treatment Due to an AE Secondary · Up to approximately 55 months

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.

GroupValue95% CI
Pembrolizumab + Lenalidomide + Dexamethasone44
Lenolidomide + Dexamethasone26

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 55 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab + Lenalidomide + Dexamethasone
Serious: 91/154 (59%)
Deaths: 51/156
Lenolidomide + Dexamethasone
Serious: 65/148 (44%)
Deaths: 43/154

Serious adverse events (176 terms)

ReactionSystemPembrolizumab + Lenalidomi…Lenolidomide + Dexamethasone
PneumoniaInfections and infestations
PyrexiaGeneral disorders
SepsisInfections and infestations
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Acute kidney injuryRenal and urinary disorders
AnaemiaBlood and lymphatic system disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Atrial fibrillationCardiac disorders
HyperthyroidismEndocrine disorders
Febrile neutropeniaBlood and lymphatic system disorders
Chest painGeneral disorders
DiverticulitisInfections and infestations
Lower respiratory tract infectionInfections and infestations
Spinal compression fractureInjury, poisoning and procedural complications
Transaminases increasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypotensionVascular disorders
NeutropeniaBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
Cardiac failureCardiac disorders
Cardio-respiratory arrestCardiac disorders
Myocardial infarctionCardiac disorders
Other adverse events (64 terms — click to expand)

ReactionSystemPembrolizumab + Lenalidomi…Lenolidomide + Dexamethasone
ConstipationGastrointestinal disorders
FatigueGeneral disorders
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
RashSkin and subcutaneous tissue disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
PyrexiaGeneral disorders
Oedema peripheralGeneral disorders
InsomniaPsychiatric disorders
Decreased appetiteMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
Weight decreasedInvestigations
ArthralgiaMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
HypocalcaemiaMetabolism and nutrition disorders
TremorNervous system disorders
Oral candidiasisInfections and infestations
Urinary tract infectionInfections and infestations
Muscle spasmsMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
Abdominal painGastrointestinal disorders
Neutrophil count decreasedInvestigations
PruritusSkin and subcutaneous tissue disorders
ThrombocytopeniaBlood and lymphatic system disorders
Dry mouthGastrointestinal disorders
DysgeusiaNervous system disorders
Neuropathy peripheralNervous system disorders
AnxietyPsychiatric disorders
HypotensionVascular disorders
Vision blurredEye disorders
NasopharyngitisInfections and infestations
PneumoniaInfections and infestations

Most-reported serious reactions: Pneumonia, Pyrexia, Sepsis, Pulmonary embolism, Acute kidney injury, Anaemia, Constipation, Diarrhoea.

Data from ClinicalTrials.gov NCT02579863 adverse events section.

Sponsor's own description

The purpose of this study is to compare the efficacy of lenalidomide and low dose dexamethasone with pembrolizumab (MK-3475) to that of lenalidomide and low dose dexamethasone without pembrolizumab in terms of progression-free survival (PFS) in participants with newly diagnosed and treatment-naïve multiple myeloma who are ineligible for autologous stem cell transplant (Auto-SCT). The study's primary hypothesis is that pembrolizumab in dexamethasone prolongs progression free survival (PFS) as assessed by Clinical Adjudication Committee (CAC) blinded central review using International Myeloma Working Group (IMWG) response criteria compared to treatment combination with lenalidomide and low-dose with lenalidomide and low-dose dexamethasone (standard of care, SOC) alone.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Immune checkpoint inhibitors: recent progress and potential biomarkers.
    Darvin P, Toor SM, Sasidharan Nair V, Elkord E. · · 2018 · cited 1495× · PMID 30546008 · DOI 10.1038/s12276-018-0191-1
  2. Genetic, transcriptional and post-translational regulation of the programmed death protein ligand 1 in cancer: biology and clinical correlations.
    Zerdes I, Matikas A, Bergh J, Rassidakis GZ, et al · · 2018 · cited 223× · PMID 29765155 · DOI 10.1038/s41388-018-0303-3
  3. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial.
    Usmani SZ, Schjesvold F, Oriol A, Karlin L, et al · · 2019 · cited 184× · PMID 31327689 · DOI 10.1016/s2352-3026(19)30109-7
  4. The Use of Immune Checkpoint Inhibitors in Oncology and the Occurrence of AKI: Where Do We Stand?
    Franzin R, Netti GS, Spadaccino F, Porta C, et al · · 2020 · cited 142× · PMID 33162990 · DOI 10.3389/fimmu.2020.574271
  5. Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies.
    Wang H, Kaur G, Sankin AI, Chen F, et al · · 2019 · cited 138× · PMID 31186046 · DOI 10.1186/s13045-019-0746-1
  6. Checkpoint inhibitors in hematological malignancies.
    Ok CY, Young KH. · · 2017 · cited 93× · PMID 28482851 · DOI 10.1186/s13045-017-0474-3
  7. Targeting immune checkpoints in hematological malignancies.
    Salik B, Smyth MJ, Nakamura K. · · 2020 · cited 92× · PMID 32787882 · DOI 10.1186/s13045-020-00947-6
  8. Update on PD-1/PD-L1 Inhibitors in Multiple Myeloma.
    Jelinek T, Paiva B, Hajek R. · · 2018 · cited 82× · PMID 30505301 · DOI 10.3389/fimmu.2018.02431

Verify or expand the search:

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Trials testing the same drug.

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