Description:
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.
Title
- 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)
Clinical Trial IDs
- ORG STUDY ID:
3475-119
- SECONDARY ID:
2015-001020-27
- SECONDARY ID:
153082
- SECONDARY ID:
MK-3475-119
- SECONDARY ID:
KEYNOTE-119
- NCT ID:
NCT02555657
Conditions
- Metastatic Triple Negative Breast Cancer
Interventions
| Drug | Synonyms | Arms |
|---|
| pembrolizumab | MK-3475, KEYTRUDA® | Pembrolizumab |
| capecitabine | XELODA® | Chemotherapy |
| eribulin | HALAVEN® | Chemotherapy |
| gemcitabine | GEMZAR® | Chemotherapy |
| vinorelbine | NAVELBINE® | Chemotherapy |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Pembrolizumab | Experimental | Participants receive pembrolizumab 200 mg intravenously (IV) every 3 weeks (Q3W) for up to 35 administrations. | |
| Chemotherapy | Active Comparator | Participants receive capecitabine, eribulin, gemcitabine, or vinorelbine as TPC in accordance with local regulations and guidelines. | - capecitabine
- eribulin
- gemcitabine
- vinorelbine
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | Overall survival (OS) was defined as the time from randomization to death due to any cause. |
Secondary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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). |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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). |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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). |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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.]) |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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.]) |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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.]) |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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) |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Merck Sharp & Dohme Corp. |
Trial Keywords
- programmed cell death receptor 1 (PD-1)
- programmed cell death ligand 1 (PD-L1)
- anti-PD-1
- anti-PD-L1
Last Updated
January 8, 2021
