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NCT02447003

Study of Pembrolizumab (MK-3475) Monotherapy for Metastatic Triple-Negative Breast Cancer (MK-3475-086/KEYNOTE-086)

Completed Phase 2 Results posted Last updated 16 December 2020
What this trial tests

Phase 2 trial testing Pembrolizumab in Breast Cancer in 254 participants. Completed in 31 January 2020.

Timeline
11 June 2015
Primary endpoint
18 February 2019
31 January 2020

Quick facts

Lead sponsorMerck Sharp & Dohme LLC
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment254
Start date11 June 2015
Primary completion18 February 2019
Estimated completion31 January 2020

Drugs / interventions tested

Conditions studied

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Breast Cancer. 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.

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Central Imaging Vendor (CIV) in All Cohort A Participants Primary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

ORR was defined as the percentage of participants who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in sum of diameters \[SOD\] of target lesions) per RECIST 1.1 by CIV. ORR was estimated by Agresti-Coull (A-C) method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort, for all participants in Cohort A. Per protocol final ORR analysis in all Cohort A participants was done at the time of

GroupValue95% CI
Cohort A: Pembrolizumab5.32.7 – 9.9
ORR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With Programmed Cell Death- Ligand 1 (PD-L1) Positive Tumor Expression Primary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for the subgroup of Cohort A participants with tumor immunohistochemistry (IHC) defined-PD-L1 positive expression (PD-L1+). Per protocol final ORR analysis in the Cohort A PD-L1+ subgroup was do

GroupValue95% CI
Cohort A: Pembrolizumab5.72.4 – 12.2
Number of Participants Who Experienced at Least One Adverse Event (AE) Primary · Up to ~31 months

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who experienced at least one AE, for the first

GroupValue95% CI
Cohort A: Pembrolizumab161
Cohort B: Pembrolizumab83
Number of Participants Who Discontinued Study Drug Due to an AE Primary · Up to ~31 months

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom or disease temporally associated with the use of a medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that is temporally associated with the use of the Sponsor's product is also an AE. Per protocol the number of participants who discontinued study drug due to an AE, in th

GroupValue95% CI
Cohort A: Pembrolizumab8
Cohort B: Pembrolizumab3
ORR Per RECIST 1.1 by CIV in All Cohort B Participants Secondary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

ORR was defined as the percentage of participants who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in SOD of target lesions) per RECIST 1.1 by CIV. ORR was estimated by A-C method. The percentage of participants who had CR or PR is reported here as the protocol-specified ORR, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort for all participants in Cohort B. Per protocol final ORR analysis in all Cohort B participants was done at the time of final statistical efficacy analysis, with a 10-Nov-2017 cutoff. Per protoco

GroupValue95% CI
Cohort B: Pembrolizumab21.413.9 – 31.4
Duration of Response (DOR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants Secondary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until progressive disease (PD: ≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by Kaplan-Meier (KM) method and analyzed by cohort is reported here fo

GroupValue95% CI
Cohort A: PembrolizumabNANA – NA
Cohort B: Pembrolizumab10.44.2 – NA
DOR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression Secondary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

For participants who had CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) per RECIST 1.1 by CIV, DOR was defined as time from first documented CR or PR until PD (≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance) or death. DOR for those who didn't progress/die at time of analysis was censored at last tumor assessment. Per protocol DOR for first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by KM method and analyzed by Cohort is reported here for subgroup of Cohort A participants with

GroupValue95% CI
Cohort A: PembrolizumabNA6.3 – NA
Disease Control Rate (DCR) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants Secondary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

DCR was defined as the percentage of participants in the analysis population who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD \[≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance\]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR, for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyz

GroupValue95% CI
Cohort A: Pembrolizumab7.64.4 – 12.7
Cohort B: Pembrolizumab23.815.9 – 34.0
DCR Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression Secondary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

DCR was defined as the percentage of participants who have CR (disappearance of all target lesions) or PR (≥30% target lesion SOD decrease) or SD (not sufficient shrinkage for PR or sufficient increase for PD \[≥20% target lesion SOD increase, ≥5 mm absolute SOD increase; PD is also ≥1 new lesion appearance\]) for ≥24 weeks per RECIST 1.1 by CIV. Per protocol percentage of participants who had CR, PR or SD per RECIST 1.1 by CIV is reported here as DCR for the first pembrolizumab course, assessed from enrolment/treatment initiation, estimated by A-C method and analyzed by Cohort for subgroup of

GroupValue95% CI
Cohort A: Pembrolizumab9.55.1 – 16.8
Progression Free Survival (PFS) Per RECIST 1.1 by CIV in All Cohort A and Cohort B Participants Secondary · Up to ~28 months (through pre-specified final statistical analysis cut-off date of 10-Nov-2017)

PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final PFS analysis in all Cohort A and Cohort B participants

GroupValue95% CI
Cohort A: Pembrolizumab2.01.9 – 2.0
Cohort B: Pembrolizumab2.12.0 – 2.2
PFS Per RECIST 1.1 by CIV in Subgroup of Cohort A Participants With PD-L1 Positive Tumor Expression Secondary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

PFS was defined as the time from first dose of study drug to the first documented PD per RECIST 1.1 by CIV, or death due to any cause, whichever occurred first. Per RECIST 1.1 PD was defined as ≥20% increase in SOD of target lesions and absolute SOD increase of ≥5 mm. Appearance of ≥1 new lesion is also PD. PFS was estimated by KM method. Per protocol PFS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for the subgroup of Cohort A participants with tumor IHC defined-PD-L1 positive expression (PD-L1+). Per protocol final

GroupValue95% CI
Cohort A: Pembrolizumab2.01.9 – 2.1
Overall Survival (OS) in All Cohort A and Cohort B Participants Secondary · Up to ~28 months (through pre-specified statistical analysis cut-off date of 10-Nov-2017)

OS was defined as the time from the first dose of study drug to death due to any cause. OS was estimated by KM method. Per protocol OS, for the first pembrolizumab course, assessed from enrolment/treatment initiation and analyzed by Cohort is reported here for all participants in Cohort A and Cohort B. Per protocol final OS analysis in all Cohort A and Cohort B participants was done at the time of final statistical efficacy analysis with a 10-Nov-2017 cutoff.

GroupValue95% CI
Cohort A: Pembrolizumab9.07.6 – 11.2
Cohort B: Pembrolizumab18.012.9 – 23.0

Adverse events — posted to ClinicalTrials.gov

Time frame: Safety: Up to ~31 months for pembrolizumab first course and up to additional ~15 months for pembrolizumab second course (AEs were collected through 90 days post treatment for SAEs and 30 days post treatment for NSAEs); All-cause mortality (ACM): Up to ~54 months for pembrolizumab first and second course. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Cohort A: Pembrolizumab First Course
Serious: 46/170 (27%)
Deaths: 154/170
Cohort A: Pembrolizumab Second Course
Serious: 0/1 (0%)
Deaths: 0/1
Cohort B: Pembrolizumab First Course
Serious: 19/84 (23%)
Deaths: 63/84
Cohort B: Pembrolizumab Second Course
Serious: 2/4 (50%)
Deaths: 0/4

Serious adverse events (68 terms)

ReactionSystemCohort A: Pembrolizumab Fi…Cohort A: Pembrolizumab Se…Cohort B: Pembrolizumab Fi…Cohort B: Pembrolizumab Se…
Pleural effusionRespiratory, thoracic and mediastinal disorders
PneumoniaInfections and infestations
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Pericardial effusionCardiac disorders
General physical health deteriorationGeneral disorders
AppendicitisInfections and infestations
Urinary tract infectionInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
Cardiac tamponadeCardiac disorders
MyocarditisCardiac disorders
PericarditisCardiac disorders
ColitisGastrointestinal disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Gastroenteritis eosinophilicGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
NauseaGastrointestinal disorders
SubileusGastrointestinal disorders
PainGeneral disorders
PyrexiaGeneral disorders
CholangitisHepatobiliary disorders
Other adverse events (52 terms — click to expand)

ReactionSystemCohort A: Pembrolizumab Fi…Cohort A: Pembrolizumab Se…Cohort B: Pembrolizumab Fi…Cohort B: Pembrolizumab Se…
FatigueGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Decreased appetiteMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DiarrhoeaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
HypothyroidismEndocrine disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
AnaemiaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Oedema peripheralGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
RashSkin and subcutaneous tissue disorders
Musculoskeletal chest painMusculoskeletal and connective tissue disorders
Aspartate aminotransferase increasedInvestigations
Musculoskeletal painMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Dry mouthGastrointestinal disorders
Chest painGeneral disorders
DizzinessNervous system disorders
AnxietyPsychiatric disorders
Weight decreasedInvestigations
HyperthyroidismEndocrine disorders
Abdominal painGastrointestinal disorders
ParaesthesiaNervous system disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
LymphoedemaVascular disorders
DepressionPsychiatric disorders
Hot flushVascular disorders
Urinary tract infectionInfections and infestations
InsomniaPsychiatric disorders
Upper respiratory tract infectionInfections and infestations
Alanine aminotransferase increasedInvestigations
Vision blurredEye disorders

Most-reported serious reactions: Pleural effusion, Pneumonia, Pulmonary embolism, Pericardial effusion, General physical health deterioration, Appendicitis, Urinary tract infection, Hyponatraemia.

Data from ClinicalTrials.gov NCT02447003 adverse events section.

Sponsor's own description

This is a two-part study of pembrolizumab monotherapy in participants with metastatic triple-negative breast cancer (mTNBC). Part 1 of the study will examine the efficacy and safety of pembrolizumab monotherapy as first line or above treatment in participants who have received either no prior systemic treatment or at least one prior systemic treatment for metastatic breast cancer. Part 2 of the study, if done, will expand the investigation of pembrolizumab treatment in a subgroup of participants from Part 1 and will only start after enrollment in Part 1 has been completed. There will be no hypothesis testing in this study.

Publications & conference data

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

  1. Triple-negative breast cancer: challenges and opportunities of a heterogeneous disease.
    Bianchini G, Balko JM, Mayer IA, Sanders ME, et al · · 2016 · cited 2163× · PMID 27184417 · DOI 10.1038/nrclinonc.2016.66
  2. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study.
    Nanda R, Chow LQ, Dees EC, Berger R, et al · · 2016 · cited 1133× · PMID 27138582 · DOI 10.1200/jco.2015.64.8931
  3. Pembrolizumab monotherapy for previously treated metastatic triple-negative breast cancer: cohort A of the phase II KEYNOTE-086 study.
    Adams S, Schmid P, Rugo HS, Winer EP, et al · · 2019 · cited 609× · PMID 30475950 · DOI 10.1093/annonc/mdy517
  4. Pembrolizumab monotherapy for previously untreated, PD-L1-positive, metastatic triple-negative breast cancer: cohort B of the phase II KEYNOTE-086 study.
    Adams S, Loi S, Toppmeyer D, Cescon DW, et al · · 2019 · cited 500× · PMID 30475947 · DOI 10.1093/annonc/mdy518
  5. Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer.
    Ye F, Dewanjee S, Li Y, Jha NK, et al · · 2023 · cited 361× · PMID 37415164 · DOI 10.1186/s12943-023-01805-y
  6. The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers.
    Tang Q, Chen Y, Li X, Long S, et al · · 2022 · cited 360× · PMID 36177034 · DOI 10.3389/fimmu.2022.964442
  7. Breast Cancer Treatments: Updates and New Challenges.
    Burguin A, Diorio C, Durocher F. · · 2021 · cited 297× · PMID 34442452 · DOI 10.3390/jpm11080808
  8. Recent advances in triple negative breast cancer: the immunotherapy era.
    Marra A, Viale G, Curigliano G. · · 2019 · cited 260× · PMID 31068190 · DOI 10.1186/s12916-019-1326-5

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