Clinical trial NCT02555657: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Metastatic Triple Negative Breast Cancer
Keywords: Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-09-21
Enrollment: 622
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall Survival in Participants With Programmed Cell Death Ligand 1 (PD-L1) With Combined Positive Score (CPS) ≥10
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Overall Survival in Participants With PD-L1 CPS ≥1
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Overall Survival in All Participants
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
Secondary outcomes:
measure: Overall Response Rate Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With PD-L1 CPS ≥10
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Overall Response Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Overall Response Rate Per RECIST 1.1 in All Participants
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥10
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Progression-Free Survival Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Progression-Free Survival Per RECIST 1.1 in All Participants
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥10 Who Had a Confirmed Response
timeFrame: 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)
measure: Duration of Response Per RECIST 1.1 in Participants With PD-L1 CPS ≥1 Who Had a Confirmed Response
timeFrame: 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)
measure: Duration of Response Per RECIST 1.1 in All Participants Who Had a Confirmed Response
timeFrame: 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)
measure: Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥10
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Disease Control Rate Per RECIST 1.1 in Participants With PD-L1 CPS ≥1
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Disease Control Rate Per RECIST 1.1 in All Participants
timeFrame: Up to approximately 36 months (through Final Analysis database cutoff date of 11-April-2019)
measure: Number of Participants Who Experienced One or More Adverse Events
timeFrame: Up to approximately 60 months
measure: Number of Participants Who Discontinued Study Treatment Due to an Adverse Event
timeFrame: Up to approximately 60 months
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.