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

• ClinicalTrials.gov Identifier: NCT02555657
• Recruitment Status: Completed
• First Posted: September 21, 2015
• Results First Posted: May 4, 2020
• Last Update Posted: December 10, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: September 18, 2015
• First Posted Date: September 21, 2015
• Results First Submitted Date: March 27, 2020
• Results First Posted Date: May 4, 2020
• Last Update Posted Date: December 10, 2021
• Actual Study Start Date: October 13, 2015
• Actual Primary Completion Date: April 11, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: September 18, 2015)

• Progression Free Survival (PFS) [ Time Frame: Up to 28 months ]
• Overall Survival (OS) [ Time Frame: Up to 28 months ]

Current Secondary Outcome Measures (submitted: November 9, 2021)

• 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 RECIST 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 RECIST 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 RECIST 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 RECIST 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 RECIST 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 RECIST 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 RECIST 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 RECIST 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 RECIST 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 RECIST 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 60 months ]
  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 Treatment Due to an Adverse Event [ Time Frame: Up to approximately 60 months ]
  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 (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: Study of Single Agent Pembrolizumab (MK-3475) Versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer (MK-3475-119/KEYNOTE-119)
• Official Title: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Metastatic Triple Negative Breast Cancer

Intervention

• 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

• Experimental: Pembrolizumab
  Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations (up to ~2 years). Qualified participants who receive first course of pembrolizumab but continue to experience disease progression may, at investigator's discretion, initiate a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to ~1 year).
  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, Munoz-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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 10, 2019): 622
• Original Estimated Enrollment (submitted: September 18, 2015): 600
• Actual Study Completion Date: November 10, 2020
• Actual Primary Completion Date: April 11, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT02555657
• Other Study ID Numbers: 3475-119; 2015-001020-27 ( EudraCT Number ); 153082 ( Registry Identifier: JAPIC-CTI ); MK-3475-119 ( Other Identifier: Merck ); 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

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: November 2021