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Study of Single Agent Pembrolizumab (MK-3475) Versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer (MK-3475-119/KEYNOTE-119)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02555657
Recruitment Status : Completed
First Posted : September 21, 2015
Results First Posted : May 4, 2020
Last Update Posted : January 8, 2021
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE September 18, 2015
First Posted Date  ICMJE September 21, 2015
Results First Submitted Date  ICMJE March 27, 2020
Results First Posted Date  ICMJE May 4, 2020
Last Update Posted Date January 8, 2021
Actual Study Start Date  ICMJE October 13, 2015
Actual Primary Completion Date April 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Overall survival (OS) was defined as the time from randomization to death due to any cause.
  • Overall Survival in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Overall survival (OS) was defined as the time from randomization to death due to any cause.
  • Overall Survival in All Participants [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Overall survival (OS) was defined as the time from randomization to death due to any cause.
Original Primary Outcome Measures  ICMJE
 (submitted: September 18, 2015)
  • Progression Free Survival (PFS) [ Time Frame: Up to 28 months ]
  • Overall Survival (OS) [ Time Frame: Up to 28 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 22, 2020)
  • Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Overall Response Rate (ORR), based on a Blinded Independent Central Review (BICR) assessment per RESIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
  • Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Overall Response Rate (ORR), based on BICR assessment per RESIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
  • Overall Response Rate Per RECIST 1.1 in All Participants [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Overall Response Rate (ORR), based on BICR assessment per RESIST 1.1, was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions).
  • Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Progression-Free Survival (PFS), based on BICR assessment per RESIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
  • Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Progression-Free Survival (PFS), based on BICR assessment per RESIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
  • Progression-Free Survival Per RECIST 1.1 in All Participants [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Progression-Free Survival (PFS), based on BICR assessment per RESIST 1.1, was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
  • Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response [ Time Frame: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019) ]
    For participants with PD-L1 CPS ≥10 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
  • Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response [ Time Frame: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019) ]
    For participants with PD-L1 CPS ≥1 who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
  • Duration of Response Per RESIST 1.1 in All Participants Who Had a Confirmed Response [ Time Frame: Up to approximately 36 months (from time of first documented evidence of CR or PR through Final Analysis database cutoff date of 11-April-2019) ]
    For participants who demonstrated a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, Duration of Response (DOR) was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions as well as an absolute increase of at least a 5 mm in the sum of diameters. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BICR.
  • Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Disease Control Rate (DCR), based on BICR assessment per RESIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.])
  • Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Disease Control Rate (DCR), based on BICR assessment per RESIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.])
  • Disease Control Rate Per RECIST 1.1 in All Participants [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    Disease Control Rate (DCR), based on BICR assessment per RESIST 1.1, was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) or Stable Disease for at least 24 weeks (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.])
  • Number of Participants Who Experienced One or More Adverse Events [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that 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, whether or not related to the medicinal product.
  • Number of Participants Who Discontinued Study Due to an Adverse Event [ Time Frame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) ]
    An adverse event (AE) is any untoward medical occurrence in a study participant administered a pharmaceutical product that 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, whether or not related to the medicinal product.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2015)
  • Overall Response Rate (ORR) [ Time Frame: Up to 28 months ]
  • Disease Control Rate (DCR) [ Time Frame: Up to 28 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Single Agent Pembrolizumab (MK-3475) Versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer (MK-3475-119/KEYNOTE-119)
Official Title  ICMJE A Randomized Open-Label Phase III Study of Single Agent Pembrolizumab Versus Single Agent Chemotherapy Per Physician's Choice for Metastatic Triple Negative Breast Cancer (mTNBC) - (KEYNOTE-119)
Brief Summary In this study, participants with metastatic triple negative breast cancer (mTNBC) will be randomly assigned to receive either single agent pembrolizumab or single agent chemotherapy chosen by the treating physician (Treatment of Physician's Choice, TPC) in accordance with local regulations and guidelines, consisting of either capecitabine, eribulin, gemcitabine, or vinorelbine. The primary study hypothesis is that pembrolizumab extends overall survival compared to TPC.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Triple Negative Breast Cancer
Intervention  ICMJE
  • Biological: pembrolizumab
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: capecitabine
    Other Name: XELODA®
  • Drug: eribulin
    Other Name: HALAVEN®
  • Drug: gemcitabine
    Other Name: GEMZAR®
  • Drug: vinorelbine
    Other Name: NAVELBINE®
Study Arms  ICMJE
  • Experimental: Pembrolizumab
    Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations.
    Intervention: Biological: pembrolizumab
  • Active Comparator: Chemotherapy
    Participants receive capecitabine, eribulin, gemcitabine, or vinorelbine as TPC in accordance with local regulations and guidelines.
    Interventions:
    • Drug: capecitabine
    • Drug: eribulin
    • Drug: gemcitabine
    • Drug: vinorelbine
Publications * Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J; KEYNOTE-119 investigators. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Apr;22(4):499-511. doi: 10.1016/S1470-2045(20)30754-3. Epub 2021 Mar 4.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2019)
622
Original Estimated Enrollment  ICMJE
 (submitted: September 18, 2015)
600
Actual Study Completion Date  ICMJE November 10, 2020
Actual Primary Completion Date April 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Centrally confirmed Stage IV/M1 mTNBC
  • Newly obtained tumor biopsy from metastatic site
  • Central determination of programmed cell death ligand 1 (PD-L1) tumor status
  • Received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on or after the most recent therapy
  • Previously treated with an anthracycline and/or taxane in the neoadjuvant/adjuvant or metastatic setting
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
  • Adequate organ function

Exclusion Criteria:

  • Participation in another clinical trial within 4 weeks
  • Monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks
  • Chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks
  • Active autoimmune disease that required systemic treatment in the past 2 years
  • Diagnosed with immunodeficiency or receiving systemic steroid therapy or another form of immunosuppressive therapy within 7 days
  • Known additional malignancy that required treatment or progressed in last 5 years
  • Known active brain metastases and/or carcinomatous meningitis
  • Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand-1 (anti-PD-L1), anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte associated protein 4 [CTLA-4], OX-40, CD137) or previously participated in any pembrolizumab (MK-3475) clinical studies
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Argentina,   Australia,   Belgium,   Brazil,   Colombia,   France,   Germany,   Guatemala,   Hong Kong,   Ireland,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Peru,   Philippines,   Poland,   Russian Federation,   Singapore,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02555657
Other Study ID Numbers  ICMJE 3475-119
2015-001020-27 ( EudraCT Number )
153082 ( Registry Identifier: JAPIC-CTI )
MK-3475-119 ( Other Identifier: Merck Protocol Number )
KEYNOTE-119 ( Other Identifier: Merck )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP