Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522)

October 27, 2025 updated by: Merck Sharp & Dohme LLC

A Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC)

The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC).

After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (Pembrolizumab + Chemotherapy OR Placebo + Chemotherapy) based on the randomization schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment. After definitive surgery, each participant will receive adjuvant study treatment (Pembrolizumab OR Placebo) for approximately 27 weeks (9 cycles). Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence.

The primary study hypothesis is that pembrolizumab is superior to placebo, in combination with chemotherapy, as measured by the rate of Pathological Complete Response (pCR) and/or Event-free Survival (EFS), in participants with locally advanced TNBC.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

1174

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Franskton, Australia, 3199
        • Frankston Hospital ( Site 2010)
      • Herston, Australia, 4029
        • Royal Brisbane and Women s Hospital ( Site 2003)
      • Perth, Australia, 6008
        • St John of God Subiaco Hospital ( Site 2006)
    • New South Wales
      • Sydney, New South Wales, Australia, 2065
        • Royal North Shore Hospital ( Site 2000)
      • Sydney, New South Wales, Australia, 2145
        • Westmead Hospital ( Site 2002)
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Royal Adelaide Hospital ( Site 2008)
    • Victoria
      • Malvern East, Victoria, Australia, 3145
        • Cabrini Health ( Site 2009)
  • Brazil
      • Cascavel, Brazil, 85806-300
        • UOPECCAN - Uniao Oeste Paranaense de Estudos e Combate ao Cancer ( Site 0206)
      • Caxias do Sul, Brazil, 95070-560
        • Universidade de Caxias do Sul ( Site 0201)
      • Curitiba, Brazil, 81520-060
        • Hospital Erasto Gaertner ( Site 0207)
      • Fortaleza, Brazil, 60430-230
        • Instituto do Cancer do Ceara ( Site 0205)
      • Goiânia, Brazil, 74605-070
        • Hospital Araujo Jorge ( Site 0204)
      • Porto Alegre, Brazil, 90610-900
        • Hospital Sao Lucas da PUCRS ( Site 0200)
      • São José do Rio Preto, Brazil, 15090-000
        • Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0208)
      • São Paulo, Brazil, 01246-000
        • Instituto do Cancer de Sao Paulo - ICESP ( Site 0211)
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
        • Hospital Nossa Senhora da Conceicao ( Site 0203)
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre ( Site 0105)
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital - Cancer Care ( Site 0100)
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre ( Site 0103)
    • Quebec
      • Montreal, Quebec, Canada, H2X 0C1
        • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital ( Site 0101)
      • Québec, Quebec, Canada, G1S 4L8
        • CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0104)
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • CIUSSS de l'Estrie-CHUS ( Site 0102)
  • Colombia
      • Bogotá, Colombia, 110231
        • Hospital Universitario San Ignacio ( Site 0401)
      • Bogotá, Colombia, 110411
        • Instituto Nacional de Cancerologia [Bogota-Colombia] ( Site 0403)
      • Cali, Colombia, 760001
        • Hemato Oncologos S.A. ( Site 0400)
      • Medellín, Colombia, 050024
        • Instituto De Cancerologia S.A. ( Site 0406)
    • Departamento de Córdoba
      • Montería, Departamento de Córdoba, Colombia, 230002
        • Oncomedica S.A. ( Site 0404)
    • Risaralda Department
      • Pereira, Risaralda Department, Colombia, 661002
        • Oncologos del Occidente S.A. ( Site 0405)
  • France
      • Besançon, France, 25000
        • CHU Jean Minjoz ( Site 0917)
      • Bordeaux, France, 33077
        • Polyclinique Bordeaux Nord Aquitaine ( Site 0911)
      • Caen, France, 14000
        • Centre Francois Baclesse ( Site 0907)
      • Clermont-Ferrand, France, 63001
        • Centre Jean Perrin ( Site 0903)
      • Le Mans, France, 72015
        • Clinique Victor Hugo ( Site 0901)
      • Nantes, France, 44277
        • Hopital prive du Confluent ( Site 0902)
      • Paris, France, 75005
        • Institut Curie ( Site 0909)
      • Paris, France, 75010
        • Hopital Saint Louis ( Site 0908)
      • Paris, France, 75020
        • Hopital Diaconesses Croix Saint Simon ( Site 0905)
      • Poitiers, France, 86021
        • CHU de la Miletrie Poitiers ( Site 0913)
      • Toulouse, France, 31059
        • Institut Claudius Regaud IUCT Oncopole ( Site 0914)
  • Germany
      • Berlin, Germany, 13125
        • HELIOS Klinikum Berlin-Buch ( Site 1005)
      • Bonn, Germany, 53111
        • Gynaekologisches Zentrum ( Site 1004)
      • Erlangen, Germany, 91054
        • Universitaetsklinikum Erlangen ( Site 1001)
      • Essen, Germany, 45136
        • Kliniken Essen Mitte ( Site 1012)
      • Halle, Germany, 06120
        • Universitaetsklinik und Poliklinik Halle/Saale ( Site 1008)
      • Hamburg, Germany, 20246
        • Universitaetsklinikum Hamburg-Eppendorf ( Site 1007)
      • München, Germany, 80337
        • Klinikum der Universit. Muenchen ( Site 1002)
      • Saarbrücken, Germany, 66113
        • Caritasklinik St. Theresia ( Site 1011)
      • Tübingen, Germany, 72076
        • Universitaets-Frauenklinik Tuebingen ( Site 1003)
  • Ireland
      • Cork, Ireland, T12 DV56
        • Bon Secours Hospital ( Site 1551)
      • Dublin, Ireland, D04 T6F4
        • St Vincents University Hospital ( Site 1550)
  • Israel
      • Beer Yaakov-Zerifin, Israel, 7030001
        • Assaf Harofeh MC ( Site 1605)
      • Beersheba, Israel, 8410101
        • Oncology institute ( Site 1601)
      • Jerusalem, Israel, 9112001
        • Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1600)
      • Petah Tikva, Israel, 4941492
        • Rabin-Medical Center ( Site 1604)
      • Ramat Gan, Israel, 5265601
        • Sheba Medical Center ( Site 1602)
      • Tel Aviv, Israel, 6423906
        • Sourasky Medical Center ( Site 1603)
  • Italy
      • Brescia, Italy, 25100
        • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 1103)
      • Lucca, Italy, 55100
        • Ospedale San Luca, AZIENDA USL2 TOSCANA NORD OVEST ( Site 1105)
      • Macerata, Italy, 62100
        • Ospedale Civile di Macerata ( Site 1104)
      • Milan, Italy, 20141
        • Istituto Europeo di Oncologia ( Site 1106)
      • Napoli, Italy, 80131
        • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1102)
    • FC
      • Meldola, FC, Italy, 47014
        • Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1101)
  • Japan
      • Chiba, Japan, 260-8717
        • Chiba Cancer Center ( Site 2519)
      • Hiroshima, Japan, 730-8518
        • Hiroshima City Hiroshima Citizens Hospital ( Site 2501)
      • Kagoshima, Japan, 892-0833
        • Social medical corporation Hakuaikai Sagara Hospital ( Site 2508)
      • Kumamoto, Japan, 860-8556
        • Kumamoto University Hospital ( Site 2515)
      • Osaka, Japan, 540-0006
        • National Hospital Organization Osaka National Hospital ( Site 2505)
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital ( Site 2500)
      • Tokyo, Japan, 104-8560
        • St.Luke's International Hospital ( Site 2511)
      • Tokyo, Japan, 105-8470
        • Toranomon Hospital ( Site 2503)
      • Tokyo, Japan, 135-8550
        • The Cancer Institute Hospital of JFCR ( Site 2509)
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 464-8681
        • Aichi Cancer Center Hospital ( Site 2502)
    • Chiba
      • Kashiwa, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East ( Site 2518)
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 003-0804
        • National Hospital Organization Hokkaido Cancer Center ( Site 2512)
    • Hyōgo
      • Nishinomiya, Hyōgo, Japan, 663-8501
        • Hyogo College of Medicine Hospital ( Site 2506)
    • Kanagawa
      • Isehara, Kanagawa, Japan, 259-1193
        • Tokai University Hospital ( Site 2517)
      • Kawasaki, Kanagawa, Japan, 216-8511
        • St. Marianna University School of Medicine Hospital ( Site 2516)
    • Osaka
      • Sayama, Osaka, Japan, 589-8511
        • Kindai University Hospital ( Site 2507)
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Saitama Medical University International Medical Center ( Site 2513)
      • Kitaadachi-gun, Saitama, Japan, 362-0806
        • Saitama Cancer Center ( Site 2510)
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center Hospital and Research Institute ( Site 2514)
  • Poland
      • Bydgoszcz, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1708)
      • Bydgoszcz, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1712)
      • Gdynia, Poland, 81-519
        • Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1701)
      • Krakow, Poland, 31-115
        • Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1719)
      • Lublin, Poland, 20-090
        • Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1700)
      • Wroclaw, Poland, 53-413
        • Dolnoslaskie Centrum Onkologii. ( Site 1702)
    • Masovian Voivodeship
      • Wieliszew, Masovian Voivodeship, Poland, 05-135
        • Mazowiecki Szpital Onkologiczny ( Site 1713)
    • Silesian Voivodeship
      • Gliwice, Silesian Voivodeship, Poland, 44-101
        • Centrum Onkologii Instytut im. Marii Skłodowskiej Curie ( Site 1717)
  • Portugal
      • Lisbon, Portugal, 1400-038
        • Fundacao Champalimaud ( Site 2444)
      • Lisbon, Portugal, 1600-190
        • Hospital de Santa Maria, E.P.E. ( Site 2445)
      • Porto, Portugal, 4200-072
        • Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2446)
  • Russia
      • Arkhangelsk, Russia, 163045
        • Arkhangelsk Clinical Oncological Dispensary ( Site 1810)
      • Chelyabinsk, Russia, 454087
        • Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1805)
      • Kazan', Russia, 420029
        • Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1806)
      • Moscow, Russia, 115478
        • Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 1801)
      • Ryazan, Russia, 390046
        • GBU RO Regional Clinical Oncological Dispensary ( Site 1808)
      • Saint Petersburg, Russia, 197758
        • Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1803)
      • Ufa, Russia, 450054
        • Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1804)
  • Singapore
      • Singapore, Singapore, 169610
        • National Cancer Centre Singapore ( Site 2600)
  • South Korea
      • Seoul, South Korea, 03080
        • Seoul National University Hospital ( Site 2101)
      • Seoul, South Korea, 03722
        • Severance Hospital Yonsei University Health System ( Site 2100)
      • Seoul, South Korea, 05505
        • Asan Medical Center ( Site 2102)
      • Seoul, South Korea, 06351
        • Samsung Medical Center ( Site 2103)
  • Spain
      • Barcelona, Spain, 08003
        • Hospital del Mar ( Site 1306)
      • Barcelona, Spain, 08023
        • Instituto Oncologico Baselga.Hospital Quiron. ( Site 1312)
      • Barcelona, Spain, 08035
        • Hospital General Universitari Vall d Hebron ( Site 1301)
      • Córdoba, Spain, 14004
        • Hospital Universitario Reina Sofia ( Site 1304)
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal ( Site 1300)
      • Santiago de Compostela, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago ( Site 1308)
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio ( Site 1314)
      • Valencia, Spain, 46011
        • Hospital Clinico Univ de Valencia ( Site 1313)
    • Barcelona
      • L'Hospitalet de Llobregat, Barcelona, Spain, 08908
        • ICO L Hospitalet ( Site 1305)
    • Madrid
      • Pozuelo de Alarcón, Madrid, Spain, 28223
        • Hospital Quiron de Madrid ( Site 1303)
  • Sweden
      • Linköping, Sweden, 581 85
        • Linkopings Universitetssjukhus ( Site 1402)
      • Solna, Sweden, 171 64
        • Karolinska Universitetssjukhuset Solna ( Site 1404)
      • Umeå, Sweden, 901 85
        • Norrlands Universitetssjukhus ( Site 1401)
      • Uppsala, Sweden, 751 85
        • Akademiska Sjukhuset ( Site 1403)
  • Taiwan
      • Tainan City, Taiwan, 704
        • National Cheng Kung University Hospital ( Site 2305)
      • Taipei, Taiwan, 100
        • National Taiwan University Hospital ( Site 2301)
      • Taipei, Taiwan, 105
        • MacKay Memorial Hospital ( Site 2303)
      • Taipei, Taiwan, 11259
        • Koo Foundation Sun Yat-Sen Cancer Center ( Site 2304)
      • Taoyuan District, Taiwan, 333
        • Linkou Chang Gung Memorial Hospital ( Site 2300)
    • Beitou
      • Taipei, Beitou, Taiwan, 11217
        • Taipei Veterans General Hospital ( Site 2302)
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01130
        • Adana Acıbadem Hospital Department of Medical Oncology ( Site 1906)
      • Adana, Turkey (Türkiye), 01250
        • Baskent Unıversity Adana Kısla Hospital ( Site 1903)
      • Ankara, Turkey (Türkiye), 06100
        • Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1912)
      • Ankara, Turkey (Türkiye), 06200
        • Abdurrahman Yurtaslan Oncology Training and Research Hospital ( Site 1909)
      • Ankara, Turkey (Türkiye), 06510
        • Ozel Medicana International Ankara Hastanesi ( Site 1915)
      • Antalya, Turkey (Türkiye), 07020
        • Antalya Memorial Hospital Department of Medical Oncology ( Site 1908)
      • Edirne, Turkey (Türkiye), 22030
        • Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1901)
      • Istanbul, Turkey (Türkiye), 34098
        • İstanbul University Cerrahpaşa Medical Faculty ( Site 1904)
      • Istanbul, Turkey (Türkiye), 34365
        • Amerikan Hospital Medical ( Site 1902)
      • Istanbul, Turkey (Türkiye), 34384
        • Memorial Sisli Hastanesi ( Site 1913)
      • Istanbul, Turkey (Türkiye), 34662
        • Acibadem Altunizade Hastanesi ( Site 1900)
      • Izmir, Turkey (Türkiye), 35040
        • Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1905)
      • Izmir, Turkey (Türkiye), 35575
        • Izmir Medical Park Hospital Department of Medical Oncology ( Site 1907)
    • Atakum
      • Samsun, Atakum, Turkey (Türkiye), 55280
        • Samsun Ondokuz Mayıs Universitesi Tıp Fakultesi Hastanesi ( Site 1910)
  • United Kingdom
      • London, United Kingdom, EC1M 6BQ
        • Barts Cancer Institute ( Site 1500)
      • London, United Kingdom, SW17 0QT
        • St George s Hospital ( Site 1516)
      • Maidstone, United Kingdom, ME16 9QQ
        • Maidstone Hospital ( Site 1511)
      • Middlesbrough, United Kingdom, TS4 3BW
        • The James Cook University Hospital ( Site 1515)
      • Nottingham, United Kingdom, NG5 1PB
        • Nottingham University Hospitals NHS Trust ( Site 1505)
      • Truro, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospitals NHS Trust ( Site 1504)
    • Essex
      • Colchester, Essex, United Kingdom, CO4 5JL
        • Colchester General Hospital ( Site 1508)
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85268
        • Virginia G. Piper Cancer Center Pharmacy - Scottsdale Healthcare ( Site 0089)
      • Tucson, Arizona, United States, 85711
        • Arizona Oncology Associates PC- HOPE ( Site 8001)
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center ( Site 0091)
      • Monterey, California, United States, 93940
        • Pacific Cancer Care ( Site 0069)
      • Whittier, California, United States, 90603
        • ICRI ( Site 0072)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center ( Site 0021)
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School of Medicine ( Site 0054)
    • Delaware
      • Newark, Delaware, United States, 19713
        • Christiana Hospital ( Site 0029)
    • Florida
      • Miami, Florida, United States, 33176
        • Univ of Miami-Sylvester Comprehensive Cancer Center- Kendall satellite ( Site 0079)
    • Illinois
      • Chicago, Illinois, United States, 60637-1447
        • The University of Chicago Medical Center ( Site 0047)
      • Evanston, Illinois, United States, 60201
        • North Shore University Health System ( Site 0081)
      • Skokie, Illinois, United States, 60077
        • Orchard Healthcare Research Inc. ( Site 0049)
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care ( Site 0010)
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • University of Iowa Hospital and Clinics ( Site 0038)
    • Maine
      • Scarborough, Maine, United States, 04074
        • New England Cancer Specialists ( Site 0005)
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Hospital ( Site 0003)
    • Minnesota
      • Minneapolis, Minnesota, United States, 55404
        • Minnesota Oncology Hematology, PA ( Site 8013)
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Rutgers Cancer Institute of New Jersey ( Site 0073)
    • New York
      • Johnson City, New York, United States, 13790
        • Broome Oncology, LLC ( Site 8002)
      • Nyack, New York, United States, 10960
        • Nyack Hospital Infusion Center ( Site 0059)
    • Ohio
      • Cincinnati, Ohio, United States, 45220
        • TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0044)
      • Cincinnati, Ohio, United States, 45242
        • Oncology Hematology Care, Inc. ( Site 8011)
    • Oregon
      • Portland, Oregon, United States, 97213
        • Providence Portland Medical Center ( Site 0052)
      • Portland, Oregon, United States, 97227
        • Northwest Cancer Specialists, P.C. ( Site 8008)
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Magee - Women's Hospital ( Site 0011)
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hospital ( Site 0060)
    • Tennessee
      • Germantown, Tennessee, United States, 38138
        • The West Clinic, P.C. ( Site 0078)
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology-Austin Central ( Site 8005)
      • Dallas, Texas, United States, 75235
        • Parkland Health and Hospital System ( Site 0093)
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8006)
      • Dallas, Texas, United States, 75390-9015
        • Simmons Cancer Center ( Site 0094)
      • Dallas, Texas, United States, 75390-9179
        • UT Southwestern Medical Center ( Site 0030)
      • Fort Worth, Texas, United States, 76104
        • Moncrief Cancer Institute ( Site 0092)
      • Houston, Texas, United States, 77024
        • Texas Oncology-Memorial City ( Site 8003)
      • Houston, Texas, United States, 77030
        • Houston Methodist Cancer Center ( Site 0013)
      • Plano, Texas, United States, 75075
        • Texas Oncology- Plano East ( Site 8010)
      • San Antonio, Texas, United States, 78217
        • Texas Oncology-San Antonio Northeast ( Site 8012)
      • Tyler, Texas, United States, 75702
        • Texas Oncology-Tyler ( Site 8007)
    • Virginia
      • Charlottesville, Virginia, United States, 22903
        • University of Virginia ( Site 0022)
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists, PC ( Site 8009)
      • Midlothian, Virginia, United States, 23114
        • Bon Secours Cancer Institute Medical Oncology at St. Mary's ( Site 0033)
      • Newport News, Virginia, United States, 23601
        • Peninsula Cancer Institute, LLC ( Site 0041)
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates ( Site 8000)
    • Washington
      • Kennewick, Washington, United States, 99336
        • Kadlec Clinic Hematology and Oncology ( Site 0087)
      • Seattle, Washington, United States, 98109
        • Seattle Cancer Care Alliance ( Site 0068)
      • Spokane, Washington, United States, 99208
        • Medical Oncology Associates (Summit Cancer Centers) ( Site 0014)
      • Yakima, Washington, United States, 98902
        • YVMH dba Vrigina Mason Memorial/North Star Lodge Cancer Center ( Site 8004)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Has newly diagnosed, locally advanced, centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.

  • Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as assessed by the investigator based on radiological and/or clinical assessment:

    • T1c, N1-N2
    • T2, N0-N2
    • T3, N0-N2
    • T4a-d, N0-N2
  • Provides a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory.
  • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
  • Demonstrates adequate organ function.
  • Males and female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and 6 months after the last dose of study treatment for participants who did not.

Exclusion Criteria:

  • Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  • Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
  • Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death - ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a pembrolizumab (MK-3475) clinical study.
  • Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 4 weeks of the first dose of treatment in this current study.
  • Has received a live vaccine within 30 days of the first dose of study treatment.
  • Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e., dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Has a known history of Human Immunodeficiency Virus (HIV).
  • Has known active Hepatitis B or Hepatitis C.
  • Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has significant cardiovascular disease, such as: history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
  • Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and for 6 months after the last dose of study treatment for participants who have not.
  • Has a known hypersensitivity to the components of the study treatment or its analogs.
  • Has a known history of active tuberculosis (TB, Bacillus Tuberculosis).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab + Chemotherapy
Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.
Drug: Doxorubicin
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
Other Names:
  • ADRIAMYCIN®
Drug: Epirubicin
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
Other Names:
  • ELLENCE®
Biological: Pembrolizumab
On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; intravenous (IV) infusion.
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Carboplatin
On Day 1 of Cycles 1-4 of the neoadjuvant phase of the study OR on Days 1, 8, 15 of Cycles 1-4 of the neoadjuvant phase of the study; IV infusion.
Other Names:
  • PARAPLATIN®
Drug: Paclitaxel
On Days 1, 8 and 15 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.
Other Names:
  • TAXOL®
Drug: Cyclophosphamide
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.
Other Names:
  • CYTOXAN®
Biological: Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim
For prevention of neutropenia, filgrastim 5 μg/kg/day via subcutaneous (SC) injection administered per standard of care after chemotherapy OR pegfilgastrim 100 µg/kg (individualized) or 6 mg (general approach) via SC injection administered per standard of care.
Other Names:
  • NEUPOGEN®
  • NEULASTA®
Active Comparator: Placebo + Chemotherapy
Participants receive placebo (normal saline solution) Q3W + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by placebo + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of placebo Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.
Drug: Doxorubicin
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
Other Names:
  • ADRIAMYCIN®
Drug: Epirubicin
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
Other Names:
  • ELLENCE®
Drug: Carboplatin
On Day 1 of Cycles 1-4 of the neoadjuvant phase of the study OR on Days 1, 8, 15 of Cycles 1-4 of the neoadjuvant phase of the study; IV infusion.
Other Names:
  • PARAPLATIN®
Drug: Paclitaxel
On Days 1, 8 and 15 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.
Other Names:
  • TAXOL®
Drug: Cyclophosphamide
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.
Other Names:
  • CYTOXAN®
Biological: Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim
For prevention of neutropenia, filgrastim 5 μg/kg/day via subcutaneous (SC) injection administered per standard of care after chemotherapy OR pegfilgastrim 100 µg/kg (individualized) or 6 mg (general approach) via SC injection administered per standard of care.
Other Names:
  • NEUPOGEN®
  • NEULASTA®
Drug: Placebo
normal saline solution or dextrose: On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
Time Frame: Up to approximately 27-30 weeks
pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.
Up to approximately 27-30 weeks
Event-free Survival (EFS) as assessed by Investigator
Time Frame: Up to approximately 8 years
EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.
Up to approximately 8 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
pCR rate using an alternative definition, ypT0 ypN0 (i.e., no invasive or noninvasive residual in breast or nodes) at the time of definitive surgery
Time Frame: Up to approximately 27-30 weeks
pCR rate (ypT0 ypN0) is defined as the percentage of participants without residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing Programmed Death-Ligand 1 (PD-L1).
Up to approximately 27-30 weeks
pCR rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery
Time Frame: Up to approximately 27-30 weeks
pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in participants with tumors expressing PD-L1.
Up to approximately 27-30 weeks
EFS in participants with tumors expressing PD-L1
Time Frame: Up to approximately 8 years
EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.
Up to approximately 8 years
pCR rate using an alternative definition, ypT0/Tis (i.e., absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement) at the time of definitive surgery
Time Frame: Up to approximately 27-30 weeks
pCR rate (ypT0/Tis) is defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery in all participants and in participants with tumors expressing PD-L1.
Up to approximately 27-30 weeks
Overall survival (OS)
Time Frame: Up to approximately 8 years
OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis will be censored at the date of the last follow-up.
Up to approximately 8 years
Percentage of participants who experience an adverse event (AE)
Time Frame: Up to approximately 61 weeks
An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.
Up to approximately 61 weeks
Percentage of participants who discontinue study treatment due to an AE
Time Frame: Up to approximately 57 weeks
An AE is defined as any untoward medical occurrence in a participant administered study treatment which does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment or protocol-specified procedure, whether or not considered related to study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of study treatment, is also an AE.
Up to approximately 57 weeks
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core 30 Questionnaire (QLQ-C30) score
Time Frame: Up to approximately 27-30 weeks
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-C30 score will be presented for all participants and for participants with tumors expressing PD-L1.
Up to approximately 27-30 weeks
EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) score
Time Frame: Up to approximately 27-30 weeks
The EORTC-QLQ-BR23 is a 23-item questionnaire developed to assess the quality of life of breast cancer patients. Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The EORTC-QLQ-BR23 score will be presented for all participants and for participants with tumors expressing PD-L1.
Up to approximately 27-30 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 7, 2017

Primary Completion (Actual)

October 14, 2025

Study Completion (Actual)

October 14, 2025

Study Registration Dates

First Submitted

January 27, 2017

First Submitted That Met QC Criteria

January 27, 2017

First Posted (Estimated)

January 30, 2017

Study Record Updates

Last Update Posted (Estimated)

October 29, 2025

Last Update Submitted That Met QC Criteria

October 27, 2025

Last Verified

October 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-522
  • 173567 (Registry Identifier: JAPIC-CTI)
  • MK-3475-522 (Other Identifier: MSD)
  • KEYNOTE-522 (Other Identifier: MSD)
  • 2016-004740-11 (EudraCT Number)
  • 2022-501382-49-00 (Registry Identifier: EU CT)
  • U1111-1280-2361 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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