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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Metastatic Triple Negative Breast Cancer

Intervention / Treatment
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* Biological: pembrolizumab
* Drug: capecitabine
* Drug: eribulin
* Drug: gemcitabine
* Drug: vinorelbine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pembrolizumab<br>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). | Biological: pembrolizumab<br> <br> * Other names: KEYTRUDA®;|
| Active Comparator: Chemotherapy<br>Participants receive capecitabine, eribulin, gemcitabine, or vinorelbine as TPC in accordance with local regulations and guidelines. | Drug: capecitabine<br> <br> * Other names: XELODA®;Drug: eribulin<br> <br> * Other names: HALAVEN®;Drug: gemcitabine<br> <br> * Other names: GEMZAR®;Drug: vinorelbine<br> <br> * Other names: NAVELBINE®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10 | Overall survival (OS) was defined as the time from randomization to death due to any cause. | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Overall Survival in Participants With PD-L1 CPS ≥1 | Overall survival (OS) was defined as the time from randomization to death due to any cause. | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Overall Survival in All Participants | Overall survival (OS) was defined as the time from randomization to death due to any cause. | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10 | 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). | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 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). | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Overall Response Rate Per RECIST 1.1 in All Participants | 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). | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | 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. | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 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. | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Progression-Free Survival Per RECIST 1.1 in All Participants | 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. | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response | 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. | 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) | 
| Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response | 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. | 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) | 
| Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response | 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. | 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) | 
| Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 | 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.]) | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 | 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.]) | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Disease Control Rate Per RECIST 1.1 in All Participants | 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.]) | Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019) | 
| Number of Participants Who Experienced One or More Adverse Events | 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. | Up to approximately 60 months | 
| Number of Participants Who Discontinued Study Treatment Due to an Adverse Event | 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. | Up to approximately 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)