Study of Pembrolizumab (MK-3475) Versus Placebo in Combination With Neoadjuvant Chemotherapy & Adjuvant Endocrine Therapy in the Treatment of Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (MK-3475-756/KEYNOTE-756)

July 8, 2025 updated by: Merck Sharp & Dohme LLC

A Randomized, Double-Blind, Phase III Study of Pembrolizumab Versus Placebo in Combination With Neoadjuvant Chemotherapy and Adjuvant Endocrine Therapy for the Treatment of High-Risk Early-Stage Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (KEYNOTE-756)

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in the treatment of adults who have high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.

The primary study hypotheses are: 1) pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pathological Complete Response (pCR) rate defined by the local pathologist, and 2) pembrolizumab is superior to placebo (both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies) as assessed by Event-Free Survival (EFS) as determined by the investigator. The study is considered to have met its primary objective if pembrolizumab is superior to placebo with respect to either pCR (ypT0/Tis ypN0) or EFS.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Study participants will receive 8 cycles of neoadjuvant study treatment and then will undergo surgery for their breast cancer. After surgery, participants will receive 9 cycles of study treatment and up to 10 years of variable endocrine therapy. Each cycle is 21 days long.

Study Type

Interventional

Enrollment (Estimated)

1240

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
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Chris OBrien Lifehouse ( Site 2107)
      • Sydney, New South Wales, Australia, 2065
        • Royal North Shore Hospital ( Site 2100)
      • Sydney, New South Wales, Australia, 2145
        • Westmead Hospital ( Site 2101)
    • Queensland
      • South Brisbane, Queensland, Australia, 4101
        • Mater Misericordiae Ltd ( Site 2106)
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Frankston Hospital ( Site 2103)
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre ( Site 2102)
  • Belgium
    • Antwerpen
      • Bonheiden, Antwerpen, Belgium, 2820
        • Imelda Ziekenhuis Bonheiden ( Site 0703)
      • Edegem, Antwerpen, Belgium, 2650
        • UZ Antwerpen - Medical Oncology ( Site 0709)
    • Bruxelles-Capitale, Region De
      • Anderlecht, Bruxelles-Capitale, Region De, Belgium, 1070
        • Institut Jules Bordet ( Site 0710)
      • Brussels, Bruxelles-Capitale, Region De, Belgium, 1200
        • Cliniques Universitaires Saint-Luc ( Site 0701)
    • Liege
      • Liège, Liege, Belgium, 4000
        • CHC MontLegia ( Site 0707)
    • Limburg
      • Hasselt, Limburg, Belgium, 3500
        • Jessa Ziekenhuis Campus Virga Jesse ( Site 0704)
    • Namur
      • Yvoir, Namur, Belgium, 5530
        • CHU UCL Namur Site de Godinne ( Site 0706)
    • Oost-Vlaanderen
      • Gent, Oost-Vlaanderen, Belgium, 9000
        • AZ Maria Middelares Gent ( Site 0700)
    • Vlaams-Brabant
      • Leuven, Vlaams-Brabant, Belgium, 3000
        • UZ Leuven ( Site 0702)
    • West-Vlaanderen
      • Kortrijk, West-Vlaanderen, Belgium, 8500
        • AZ Groeninge ( Site 0705)
  • Brazil
      • Rio de Janeiro, Brazil, 20560121
        • Instituto Nacional de Câncer - INCA-Pesquisa Clinica HC3 ( Site 0200)
      • Sao Paulo, Brazil, 01317-001
        • Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 0204)
      • Sao Paulo, Brazil, 12460-000
        • Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0209)
      • Sao Paulo, Brazil, 04014-002
        • Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0210)
    • Goias
      • Goiania, Goias, Brazil, 74605-070
        • Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 0205)
    • Rio Grande Do Sul
      • Ijui, Rio Grande Do Sul, Brazil, 98700-000
        • ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0206)
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-001
        • Associacao Hospitalar Moinhos de Vento ( Site 0201)
      • Porto Alegre, Rio Grande Do Sul, Brazil, 90610-000
        • Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0202)
    • Santa Catarina
      • Florianopolis, Santa Catarina, Brazil, 88034-000
        • CEPON - Centro de Pesquisas Oncologicas ( Site 0208)
      • Itajai, Santa Catarina, Brazil, 88301-220
        • Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0207)
  • Canada
      • Quebec, Canada, G1S 4L8
        • CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0101)
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute ( Site 0115)
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • BC Cancer-Vancouver Center ( Site 0116)
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre ( Site 0112)
    • Quebec
      • Greenfield Park, Quebec, Canada, J4V 2H1
        • CISSS de la Monteregie-Centre ( Site 0108)
      • Montreal, Quebec, Canada, H1T 2M4
        • Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0111)
      • Montreal, Quebec, Canada, H2X 3E4
        • Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0114)
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital ( Site 0103)
      • Trois-Rivières, Quebec, Canada, G8Z 3R9
        • Centre Hospitalier Regional de Trois-Rivieres ( Site 0106)
  • China
    • Anhui
      • Heifei, Anhui, China, 230001
        • Anhui Provincial Hospital ( Site 3224)
      • Shanghai, Anhui, China, 200025
        • Ruijin Hosp,Shanghai Jiao Tong University School of Medicine ( Site 3215)
    • Beijing
      • Beijing, Beijing, China, 100021
        • Cancer Hospital Chinese Academy of Medical Sciences ( Site 3208)
    • Fujian
      • Fuzhou Fujian, Fujian, China, 350001
        • Fujian Medical University Union Hospital-1 Bingfanglou-Oncology ( Site 3207)
    • Guangdong
      • Guangzhou, Guangdong, China, 510289
        • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 3213)
    • Hebei
      • Shijia Zhuang, Hebei, China, 050019
        • Fourth Hospital Of Hebei Medical University ( Site 3216)
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Harbin Medical University Cancer Hospital ( Site 3200)
    • Henan
      • Zhengzhou, Henan, China, 450008
        • Henan Cancer Hospital ( Site 3212)
    • Hubei
      • Wuhan, Hubei, China, 430079
        • Hubei Cancer Hospital ( Site 3211)
    • Hunan
      • Changsha, Hunan, China, 410013
        • Hunan Cancer Hospital ( Site 3214)
    • Jiangsu
      • Hangzhou, Jiangsu, China, 310003
        • The First Affiliated Hospital of Zhejiang University ( Site 3203)
    • Jilin
      • Changchun, Jilin, China, 130021
        • The First Hospital of Jilin University ( Site 3201)
    • Shanghai
      • Shanghai, Shanghai, China, 200032
        • Fudan University Shanghai Cancer Center ( Site 3205)
    • Shanxi
      • XI An, Shanxi, China, 710061
        • The First Affiliated Hospital of Xi an Jiaotong University ( Site 3220)
    • Tianjin
      • Tianjin, Tianjin, China, 300060
        • Tianjin Medical University Cancer Institute & Hospital ( Site 3209)
    • Xinjiang
      • Urumqi, Xinjiang, China, 830000
        • The Affiliated Cancer Hospital of Xinjiang Medical ( Site 3219)
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310014
        • Zhejiang Provincial People's Hospital ( Site 3225)
      • Hangzhou, Zhejiang, China, 310022
        • Zhejiang Cancer Hospital ( Site 3210)
  • Colombia
    • Antioquia
      • Medellin, Antioquia, Colombia, 050030
        • Fundacion Colombiana de Cancerología Clinica Vida ( Site 0405)
      • Medellin, Antioquia, Colombia, 50030
        • Rodrigo Botero SAS ( Site 0407)
    • Atlantico
      • Barranquilla, Atlantico, Colombia, 080020
        • Clinica de la Costa S.A.S. ( Site 0400)
    • Cordoba
      • Monteria, Cordoba, Colombia, 230002
        • IMAT S.A.S ( Site 0401)
    • Distrito Capital De Bogota
      • Bogota, Distrito Capital De Bogota, Colombia, 110221
        • Centro de Investigacion Clinica del Country ( Site 0402)
      • Bogota, Distrito Capital De Bogota, Colombia, 111221
        • Fundacion Universitaria Sanitas ( Site 0403)
    • Valle Del Cauca
      • Cali, Valle Del Cauca, Colombia, 760042
        • Clínica Imbanaco S.A.S ( Site 0406)
  • Costa Rica
    • San Jose
      • Santa Ana, San Jose, Costa Rica, 10903
        • Hospital Metropolitano - Sede Lindora ( Site 4203)
  • France
      • Paris, France, 75005
        • Institut Curie ( Site 0900)
      • Paris, France, 75010
        • Hopital Saint-Louis ( Site 0908)
      • Paris, France, 75020
        • Hopital Tenon ( Site 0914)
    • Calvados
      • Caen, Calvados, France, 14076
        • Centre Francois Baclesse ( Site 0927)
    • Cote-d Or
      • Dijon, Cote-d Or, France, 21079
        • Centre Georges Francois Leclerc ( Site 0920)
    • Haute-Garonne
      • Toulouse, Haute-Garonne, France, 31059
        • Institut Claudius Regaud IUCT Oncopole ( Site 0903)
    • Hauts-de-Seine
      • Saint-Cloud, Hauts-de-Seine, France, 92210
        • Institut Curie - Centre Rene Huguenin ( Site 0917)
    • Herault
      • Montpellier, Herault, France, 34070
        • Centre de Cancerologie du Grand Montpellier ( Site 0925)
    • Moselle
      • Metz, Moselle, France, 57085
        • CHR-METZ-THIONVILLE - Hopital de Mercy ( Site 0919)
    • Nord-Pas-de-Calais
      • Lille, Nord-Pas-de-Calais, France, 59000
        • Centre Oscar Lambret ( Site 0911)
    • Provence-Alpes-Cote-d Azur
      • Avignon, Provence-Alpes-Cote-d Azur, France, 84918
        • Institut Sainte Catherine ( Site 0916)
    • Puy-de-Dome
      • Clermont Ferrand Cedex, Puy-de-Dome, France, 63011
        • Centre Jean Perrin ( Site 0909)
    • Sarthe
      • Le Mans, Sarthe, France, 72000
        • Clinique Victor Hugo Le Mans ( Site 0906)
    • Val-de-Marne
      • Villejuif, Val-de-Marne, France, 94800
        • Institut Gustave Roussy ( Site 0926)
  • Germany
    • Baden-Wurttemberg
      • Friedrichshafen, Baden-Wurttemberg, Germany, 88045
        • Medizinische Management GmbH ( Site 1012)
    • Bayern
      • Erlangen, Bayern, Germany, 91054
        • Universitaetsklinikum Erlangen ( Site 1001)
      • Muenchen, Bayern, Germany, 80336
        • Klinikum der Universitaet Muenchen - Grosshadern ( Site 1000)
    • Hessen
      • Offenbach, Hessen, Germany, 63069
        • Sana Klinikum Offenbach GmbH ( Site 1002)
      • Wiesbaden, Hessen, Germany, 65199
        • HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 1004)
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30177
        • MVZ Onko Medical GmbH Hannover ( Site 1013)
    • Nordrhein-Westfalen
      • Bonn, Nordrhein-Westfalen, Germany, 53111
        • Gynaekologisches Zentrum ( Site 1003)
      • Essen, Nordrhein-Westfalen, Germany, 45136
        • Kliniken Essen Mitte Gmbh Evang. Huyssens Stiftung ( Site 1006)
      • Paderborn., Nordrhein-Westfalen, Germany, 33098
        • Frauenklinik St. Louise ( Site 1014)
    • Saarland
      • Saarbruecken, Saarland, Germany, 66113
        • Caritas Klinikum Saarbruecken St. Theresia ( Site 1009)
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Universitaetsklinikum Carl Gustav Carus ( Site 1008)
    • Thuringen
      • Nordhausen, Thuringen, Germany, 99734
        • MVZ Nordhausen gGmbH - Praxis Dr. Grafe ( Site 1005)
  • Hungary
      • Budapest, Hungary, 1122
        • Orszagos Onkologiai Intezet ( Site 2908)
      • Budapest, Hungary, 1032
        • Budapesti Szent Margit Korhaz ( Site 2901)
      • Budapest, Hungary, 1145
        • Budapesti Uzsoki Utcai Kórház-Onkoradiológiai Osztály ( Site 2902)
      • Debrecen, Hungary, 4032
        • Debreceni Egyetem Klinikai Kozpont ( Site 2907)
      • Kaposvar, Hungary, 7400
        • Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 2915)
    • Bacs-Kiskun
      • Kecskemét, Bacs-Kiskun, Hungary, 6000
        • Bacs-Kiskun Varmegyei Oktatokorhaz-Onkoradiologiai Kozpont ( Site 2913)
    • Baranya
      • Pecs, Baranya, Hungary, 7621
        • Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 2905)
    • Borsod-Abauj-Zemplen
      • Miskolc, Borsod-Abauj-Zemplen, Hungary, 3526
        • Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 2904)
  • Ireland
      • Cork, Ireland, T12 DV56
        • Bon Secours Hospital ( Site 1554)
      • Dublin, Ireland, Dublin 8
        • St. James s Hospital ( Site 1553)
  • Israel
      • Afula, Israel, 1834111
        • HaEmek Medical Center ( Site 1712)
      • Ashdod, Israel, 7747629
        • Assuta Ashdod Public ( Site 1704)
      • Beer Sheva, Israel, 8410101
        • Soroka Medical Center ( Site 1701)
      • Haifa, Israel, 3109601
        • Rambam Health Care Campus-Oncology Division ( Site 1705)
      • Jerusalem, Israel, 9103102
        • Shaare Zedek Medical Center ( Site 1708)
      • Jerusalem, Israel, 9112001
        • Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1700)
      • Kfar-Saba, Israel, 4428164
        • Meir Medical Center ( Site 1710)
      • Nazareth, Israel, 1641101
        • Holy Family Hospital ( Site 1711)
      • Petah Tikva, Israel, 4941 492
        • Rabin Medical Center ( Site 1702)
      • Ramat Gan, Israel, 5262000
        • Chaim Sheba Medical Center. ( Site 1707)
      • Rehovot, Israel, 76100
        • Kaplan Medical Center ( Site 1703)
      • Tel Aviv, Israel, 6423906
        • Sourasky Medical Center ( Site 1706)
      • Tel Aviv, Israel, 6789140
        • Assuta Medical Center ( Site 1709)
  • Japan
      • Chiba, Japan, 260-8717
        • Chiba Cancer Center ( Site 2605)
      • Fukushima, Japan, 960-1295
        • Fukushima Medical University Hospital ( Site 2610)
      • Hiroshima, Japan, 730-8518
        • Hiroshima City Hiroshima Citizens Hospital ( Site 2603)
      • Osaka, Japan, 540-0006
        • National Hospital Organization Osaka National Hospital ( Site 2614)
      • Tokyo, Japan, 105-8470
        • Toranomon Hospital ( Site 2608)
      • Tokyo, Japan, 135-8550
        • Cancer Institute Hospital of JFCR ( Site 2604)
      • Tokyo, Japan, 142-8666
        • Showa Medical University Hospital ( Site 2615)
    • Aichi
      • Nagoya, Aichi, Japan, 464-8681
        • Aichi Cancer Center ( Site 2601)
    • Chiba
      • Kashiwa, Chiba, Japan, 2778577
        • National Cancer Center Hospital East ( Site 2613)
    • Hokkaido
      • Sapporo, Hokkaido, Japan, 003-0804
        • National Hospital Organization Hokkaido Cancer Center ( Site 2607)
    • Hyogo
      • Nishinomiya, Hyogo, Japan, 663-8501
        • Hyogo Medical University Hospital ( Site 2600)
    • Kanagawa
      • Sagamihara, Kanagawa, Japan, 252-0375
        • Kitasato University Hospital ( Site 2616)
    • Kumamoto
      • Kumamoto-shi, Kumamoto, Japan, 860-8556
        • Kumamoto University Hospital ( Site 2602)
    • Saitama
      • Hidaka, Saitama, Japan, 350-1298
        • Saitama Medical University International Medical Center ( Site 2606)
      • Kitaadachi-gun, Saitama, Japan, 362-0806
        • Saitama Prefectural Cancer Center ( Site 2612)
    • Shizuoka
      • Suntogun, Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center ( Site 2611)
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital ( Site 2200)
      • Seoul, Korea, Republic of, 03722
        • Severance Hospital Yonsei University Health System ( Site 2201)
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center ( Site 2203)
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center ( Site 2202)
    • Kyonggi-do
      • Goyang-si, Kyonggi-do, Korea, Republic of, 10408
        • National Cancer Center ( Site 2204)
  • New Zealand
      • Wellington, New Zealand, 6021
        • Capital & Coast District Health Board - Wellington Hospital ( Site 2301)
    • Bay Of Plenty
      • Tauranga, Bay Of Plenty, New Zealand, 3112
        • Tauranga Hospital ( Site 2302)
    • Canterbury
      • Christchurch, Canterbury, New Zealand, 8011
        • Canterbury Regional Cancer & Blood Services ( Site 2303)
  • Poland
    • Dolnoslaskie
      • Wrocław, Dolnoslaskie, Poland, 53-413
        • Dolnoslaskie Centrum Onkologii. ( Site 1820)
    • Kujawsko-pomorskie
      • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
        • Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1800)
    • Lodzkie
      • Lodz, Lodzkie, Poland, 93-338
        • Instytut Centrum Zdrowia Matki Polki ( Site 1821)
    • Mazowieckie
      • Ostroleka, Mazowieckie, Poland, 07-410
        • Mazowiecki Szpital Specjalistyczny im. dr Jozefa Psarskiego ( Site 1814)
      • Warszawa, Mazowieckie, Poland, 02-781
        • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 1899)
      • Wieliszew, Mazowieckie, Poland, 05-135
        • Mazowiecki Szpital Onkologiczny ( Site 1803)
    • Podlaskie
      • Bialystok, Podlaskie, Poland, 15-027
        • Bialostockie Centrum Onkologii ( Site 1819)
    • Pomorskie
      • Gdansk, Pomorskie, Poland, 80-219
        • Wojewodzkie Centrum Onkologii Copernicus ( Site 1817)
      • Gdynia, Pomorskie, Poland, 81-519
        • Szpitale Pomorskie Sp. z o.o. ( Site 1818)
    • Slaskie
      • Bielsko-Biala, Slaskie, Poland, 43-300
        • Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1810)
      • Bytom, Slaskie, Poland, 41-900
        • Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1807)
      • Gliwice, Slaskie, Poland, 44-101
        • Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1801)
  • Portugal
      • Lisboa, Portugal, 1649-035
        • Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 2501)
      • Porto, Portugal, 4200-072
        • Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 2502)
      • Porto, Portugal, 4099-001
        • Unidade Local de Saude de Santo António - Hospital Santo António ( Site 2503)
    • Aveiro
      • Lisboa, Aveiro, Portugal, 1400-038
        • Fundacao Champalimaud ( Site 2500)
  • Puerto Rico
      • San Juan, Puerto Rico, 00935
        • UPR Comprehensive Cancer Center ( Site 6200)
  • Russian Federation
    • Arkhangel Skaya Oblast
      • Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation, 163045
        • Arkhangelsk Clinical Oncological Dispensary ( Site 1901)
    • Baskortostan, Respublika
      • Ufa, Baskortostan, Respublika, Russian Federation, 450054
        • Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1909)
    • Moskva
      • Moscow, Moskva, Russian Federation, 115478
        • N.N. Blokhin NMRCO ( Site 1908)
      • Moscow, Moskva, Russian Federation, 121359
        • Central Clinical Hospital with outpatient Clinic ( Site 1907)
      • Moscow, Moskva, Russian Federation, 125367
        • Medical Rehabilitation Center ( Site 1912)
    • Ryazanskaya Oblast
      • Ryazan, Ryazanskaya Oblast, Russian Federation, 390046
        • Ryazan Regional Clinical Oncology Dispensary ( Site 1910)
    • Sankt-Peterburg
      • Saint Petersburg, Sankt-Peterburg, Russian Federation, 195271
        • Railway Hospital of OJSC ( Site 1913)
      • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197758
        • Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1900)
    • Tatarstan, Respublika
      • Kazan, Tatarstan, Respublika, Russian Federation, 420029
        • Republican Clinical Oncology Dispensary of Tatarstan MoH named after professor M.Z. Sigal ( Site 1903)
    • Tomskaya Oblast
      • Tomsk, Tomskaya Oblast, Russian Federation, 634028
        • Tomsk Scientific Research Institute of Oncology ( Site 1905)
  • Spain
      • Barcelona, Spain, 08023
        • Instituto Oncologico Baselga.Hospital Quiron. ( Site 1352)
      • Barcelona, Spain, 08035
        • Hospital Vall D Hebron ( Site 1357)
      • Barcelona, Spain, 08036
        • Hospital Clinic I Provincial de Barcelona ( Site 1353)
      • Jaen, Spain, 23007
        • Complejo Hospitalario de Jaen ( Site 1364)
      • Madrid, Spain, 28040
        • Hospital Clinico San Carlos ( Site 1354)
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre ( Site 1356)
      • Madrid, Spain, 28007
        • Hospital Beata María Ana-oncology ( Site 1370)
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen del Rocio ( Site 1360)
      • Valencia, Spain, 46015
        • Hospital General Arnau de Vilanova de Valencia ( Site 1369)
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08908
        • Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1363)
    • La Coruna
      • A Coruna, La Coruna, Spain, 15006
        • Hospital Teresa Herrera - Chuac ( Site 1358)
    • Madrid
      • Pozuelo de Alarcon, Madrid, Spain, 28223
        • Hospital Quiron de Madrid ( Site 1351)
    • Madrid, Comunidad De
      • Madrid, Madrid, Comunidad De, Spain, 28007
        • Hospital General Universitario Gregorio Maranon ( Site 1367)
    • Valenciana, Comunitat
      • Valencia, Valenciana, Comunitat, Spain, 46011
        • Hospital Clinico Universitario de Valencia ( Site 1355)
  • Taiwan
      • Taichung, Taiwan, 40447
        • China Medical University Hospital ( Site 2401)
      • Tainan, Taiwan, 70457
        • National Cheng Kung University Hospital ( Site 2400)
      • Taipei, Taiwan, 11259
        • Koo Foundation Sun Yat-Sen Cancer Center ( Site 2403)
      • Taipei, Taiwan, 100225
        • National Taiwan University Hospital ( Site 2404)
      • Taoyuan, Taiwan, 333
        • Linkou Chang Gung Memorial Hospital ( Site 2402)
  • Ukraine
      • Kyiv, Ukraine, 03115
        • Kyiv City Clinical Oncology Centre ( Site 2716)
    • Dnipropetrovska Oblast
      • Dnipro, Dnipropetrovska Oblast, Ukraine, 49102
        • MNPE City Clinical Hospital #4 of Dnipro Regional Council ( Site 2702)
      • Kryviy Rih, Dnipropetrovska Oblast, Ukraine, 50048
        • MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2700)
    • Ivano-Frankivska Oblast
      • Ivano-Frankivsk, Ivano-Frankivska Oblast, Ukraine, 76018
        • MI Precarpathian Clinical Oncology Center ( Site 2707)
    • Kharkivska Oblast
      • Kharkiv, Kharkivska Oblast, Ukraine, 61070
        • Communal non profit enterprise Regional Clinical Oncology Center ( Site 2721)
    • Khersonska Oblast
      • Antonivka Village, Khersonska Oblast, Ukraine, 73000
        • Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council ( Site 2713)
    • Khmelnytska Oblast
      • Khmelnitskiy, Khmelnytska Oblast, Ukraine, 29000
        • Khmelnitskiy Regional Onkology Dispensary ( Site 2704)
    • Kyivska Oblast
      • Kyiv, Kyivska Oblast, Ukraine, 03022
        • SNPE National Cancer Institute ( Site 2719)
    • Odeska Oblast
      • Odesa, Odeska Oblast, Ukraine, 65025
        • MI Odesa Regional Clinical Hospital ( Site 2701)
      • Odesa, Odeska Oblast, Ukraine, 65055
        • MI Odessa Regional Oncological Centre ( Site 2714)
    • Zaporizka Oblast
      • Zaporizhzhia, Zaporizka Oblast, Ukraine, 69035
        • Medical center of the Limited Liability Company Yulis ( Site 2720)
  • United Kingdom
      • Solihull, United Kingdom, B91 2JL
        • Birmingham & Solihull Heartlands Hospital NHS ( Site 1506)
      • Truro, United Kingdom, TR1 3LJ
        • Royal Cornwall Hospital ( Site 1502)
    • Bristol, City Of
      • Bristol, Bristol, City Of, United Kingdom, BS2 8ED
        • University Hospitals Bristol NHS Foundation Trust ( Site 1503)
    • England
      • Nottingham, England, United Kingdom, NG5 1PF
        • Nottingham University Hospitals NHS Trust ( Site 1504)
    • Essex
      • Colchester, Essex, United Kingdom, CO4 5JL
        • Colchester General Hospital ( Site 1508)
    • London, City Of
      • London, London, City Of, United Kingdom, EC1A 7BE
        • Barts Health NHS Trust ( Site 1500)
      • London, London, City Of, United Kingdom, SE1 9RY
        • Guy's Hospital ( Site 1501)
      • London, London, City Of, United Kingdom, SW17 0QT
        • St. Georges University Hospital NHS Foundation Trust ( Site 1505)
  • United States
    • Alabama
      • Daphne, Alabama, United States, 36526
        • Southern Cancer Center, PC ( Site 8003)
    • Arizona
      • Goodyear, Arizona, United States, 85338
        • Cancer Treatment Centers of America at Western Regional Medical Center ( Site 0001)
      • Tucson, Arizona, United States, 85704
        • Arizona Oncology Associates PC- HOPE ( Site 8008)
    • California
      • Los Angeles, California, United States, 90048
        • Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0079)
      • Mountain View, California, United States, 94040
        • El Camino Hospital Cancer Center ( Site 0004)
      • Palo Alto, California, United States, 94304
        • Stanford Cancer Center ( Site 0072)
      • Sacramento, California, United States, 95817
        • UC Davis Comprehensive Cancer Center ( Site 0073)
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado, Anschutz Cancer Pavilion ( Site 0008)
    • Florida
      • Jacksonville, Florida, United States, 32207
        • Baptist MD Anderson Cancer Center ( Site 0014)
    • Georgia
      • Newnan, Georgia, United States, 30265
        • Southeastern Regional Medical Center, Inc. ( Site 0075)
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center ( Site 0080)
      • Skokie, Illinois, United States, 60077
        • Orchard Healthcare Research Inc. ( Site 0020)
      • Zion, Illinois, United States, 60099
        • Midwestern Regional Medical Center, Inc. ( Site 0077)
    • Indiana
      • Goshen, Indiana, United States, 46526
        • Goshen Center for Cancer Care ( Site 0021)
    • Iowa
      • Waterloo, Iowa, United States, 50702
        • MercyOne Waterloo Cancer Center ( Site 0016)
    • Kentucky
      • Louisville, Kentucky, United States, 40202
        • James Graham Brown Cancer Center ( Site 0022)
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • Maryland Oncology Hematology, P.A. ( Site 8007)
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ( Site 0024)
      • Danvers, Massachusetts, United States, 01923
        • MGH - North Shore Cancer Center ( Site 0081)
      • Newton, Massachusetts, United States, 02462
        • MGH Newton-Wellesley Hospital's Vernon Cancer Center ( Site 0082)
    • Michigan
      • Detroit, Michigan, United States, 48202
        • Henry Ford Health System ( Site 0028)
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic and Medical School (Rochester) ( Site 0029)
    • Montana
      • Billings, Montana, United States, 59102
        • St. Vincent Frontier Cancer Center ( Site 0033)
    • Nebraska
      • Omaha, Nebraska, United States, 68130
        • Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0039)
    • New Jersey
      • Teaneck, New Jersey, United States, 07666
        • Holy Name Medical Center ( Site 0041)
    • New York
      • New York, New York, United States, 10065
        • Weill Cornell Medical College ( Site 0043)
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74133
        • CTCA Southwestern ( Site 0074)
    • Oregon
      • Portland, Oregon, United States, 97239
        • OHSU Knight Cancer Institute ( Site 0051)
      • Tigard, Oregon, United States, 97223
        • Northwest Cancer Specialists, P.C. ( Site 8000)
    • Pennsylvania
      • Danville, Pennsylvania, United States, 17822
        • Geisinger Medical Center ( Site 0052)
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center ( Site 0078)
      • Philadelphia, Pennsylvania, United States, 19124
        • Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0076)
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Medical University of South Carolina ( Site 0053)
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000)
    • Texas
      • Austin, Texas, United States, 78731
        • Texas Oncology-Austin Central ( Site 8004)
      • Dallas, Texas, United States, 75231
        • Texas Oncology-Dallas Presbyterian Hospital ( Site 8002)
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8009)
      • Houston, Texas, United States, 77024
        • Texas Oncology-Memorial City ( Site 8012)
      • Houston, Texas, United States, 77030
        • University of Texas-MD Anderson Cancer Center ( Site 0083)
      • Plano, Texas, United States, 75075
        • Texas Oncology- Plano East ( Site 8010)
      • Tyler, Texas, United States, 75702
        • Texas Oncology - Northeast Texas ( Site 8006)
    • Virginia
      • Midlothian, Virginia, United States, 23114
        • Bon Secours St. Francis Medical Center Oncology Research ( Site 0064)
      • Norfolk, Virginia, United States, 23502
        • Virginia Oncology Associates ( Site 8001)
    • Washington
      • Kennewick, Washington, United States, 99336
        • Kadlec Clinic Hematology and Oncology ( Site 0070)
      • Spokane, Washington, United States, 99208
        • Medical Oncology Associates (Summit Cancer Centers) ( Site 0066)

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

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Has a localized invasive breast ductal adenocarcinoma, confirmed by the local pathologist, that includes either T1c-T2 (tumor size ≥2 cm), clinical node stage (cN)1-cN2, or T3-T4, cN0-cN2. Note: Inflammatory breast cancer is allowed.
  • Has centrally confirmed ER+/HER2-, Grade 3 breast cancer of ductal histology, according to the most recent American Society of Clinical Oncology/College of American Pathologist guidelines.
  • Provides a new or recently obtained core needle biopsy, consisting of multiple cores, taken from the primary breast tumor(s) for central determination of HR status (ER and progesterone receptor), HER2, grade, and PD-L1 status.

Note: Sponsor agreement is required for formalin-fixed paraffin-embedded (FFPE) tumor tissue sample or slides that were obtained greater than 60 days prior to the date that the documented informed consent was obtained.

  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment.
  • Male participants must agree to use contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment and refrain from donating sperm during this period.
  • Female participants must agree to use effective contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment with pembrolizumab or placebo.
  • Has adequate organ function.

Exclusion Criteria:

  • Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis.
  • Has breast cancer with lobular histology.
  • Has bilateral invasive breast cancer.
  • Has metastatic (Stage IV) breast cancer.
  • Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast).
  • Has any of the following clinical lymph node staging per current American Joint Committee on Cancer (AJCC) staging criteria for breast cancer staging based on radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c.
  • Has ER-, progesterone receptor positive breast cancer.
  • Has undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment.
  • Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years.

Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal breast carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded.

  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
  • Has a known history of active tuberculosis (Bacillus tuberculosis).
  • Has an active infection requiring systemic therapy.
  • Has left ventricular ejection fraction (LVEF) of <50% or below the institution limit of normal, as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
  • Has other significant cardiac disease, such as: 1) History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months. or 2) Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a known history of hepatitis B or known active hepatitis C virus infection.
  • Has received prior treatment for breast cancer.
  • Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
  • Has received a live vaccine within 30 days prior to the first dose of study treatment.
  • Has severe hypersensitivity (≥Grade 3) to any of the components or excipients used in the study treatments.
  • Is/was enrolled in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks (12 months for an investigational agent or device with anticancer or antiproliferative properties) prior to the first dose of study treatment.
  • Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment.

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pembrolizumab+Chemotherapy (KX/KA[E]C)
In the neoadjuvant setting, participants receive pembrolizumab (K) 200 mg via intravenous (IV) infusion once every 3 weeks (Q3W) + paclitaxel (X) 80 mg/m^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by pembrolizumab 200 mg via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m^2 or 100 mg/m^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive pembrolizumab 200 mg via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.
Procedure: Surgery
Surgery for breast cancer
Biological: Pembrolizumab (K)
IV infusion Q3W
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Paclitaxel (X)
IV infusion QW
Other Names:
  • TAXOL®
Drug: Doxorubicin (A)
IV infusion either in Q2W or Q3W
Other Names:
  • ADRIAMYCIN®
Drug: Epirubicin (E)
IV infusion either in Q2W or Q3W
Other Names:
  • ELLENCE®
Drug: Cyclophosphamide (C)
IV infusion either in Q2W or Q3W
Other Names:
  • CYTOXAN®
Drug: Endocrine therapy
Variable endocrine therapy for up 10 years
Radiation: Radiation therapy
Variable radiation therapy per local standard of care
Placebo Comparator: Placebo+Chemotherapy (PX/PA[E]C)
In the neoadjuvant setting, participants receive placebo (P; normal saline or dextrose) via IV infusion Q3W + paclitaxel (X) 80 mg/m^2 via IV infusion once weekly (QW) for 4 cycles (Treatment 1), followed by placebo via IV infusion + doxorubicin or epirubicin (A or E; 60 mg/m^2 or 100 mg/m^2) via IV infusion either in Q2W or Q3W + cyclophosphamide (C) 600 mg/m^2 via IV infusion either in Q2W or Q3W for 4 cycles (Treatment 2). At no more than 6 weeks after last cycle of neoadjuvant treatment, participants will undergo surgery for their breast cancer. After surgery, participants will begin adjuvant study treatment. In the adjuvant setting, participants receive placebo via IV infusion Q3W for 9 cycles + variable endocrine therapy for up to 10 years. Each cycle is 21 days long.
Procedure: Surgery
Surgery for breast cancer
Drug: Paclitaxel (X)
IV infusion QW
Other Names:
  • TAXOL®
Drug: Doxorubicin (A)
IV infusion either in Q2W or Q3W
Other Names:
  • ADRIAMYCIN®
Drug: Epirubicin (E)
IV infusion either in Q2W or Q3W
Other Names:
  • ELLENCE®
Drug: Cyclophosphamide (C)
IV infusion either in Q2W or Q3W
Other Names:
  • CYTOXAN®
Radiation: Radiation therapy
Variable radiation therapy per local standard of care
Drug: Placebo (P)
Normal saline or dextrose IV infusion Q3W

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
Time Frame: Up to approximately 7 months (Time of surgery)
The 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 American Joint Committee on Cancer (AJCC) staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pathological Complete Response (pCR) using the definition of (ypT0/Tis ypN0) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
Up to approximately 7 months (Time of surgery)
Event-Free Survival (EFS)
Time Frame: Up to approximately 12 years
EFS is defined as the time from randomization to disease progression that: precludes surgery, results in a local or distant recurrence, results in a second primary malignancy, or death due to any cause whichever occurs first. The EFS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator will be presented.
Up to approximately 12 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Up to approximately 12 years
OS is defined as the time from date of randomization to date of death due to any cause. The OS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies will be presented.
Up to approximately 12 years
pCR Rate Using the Definition of ypT0ypN0
Time Frame: Up to approximately 7 months (Time of surgery)
pCR rate (ypT0ypN0) is defined as the percentage of participants without residual invasive or in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy by AJCC staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pCR using the definition of (ypT0ypN0) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
Up to approximately 7 months (Time of surgery)
pCR Rate Using the Definition of ypT0/Tis
Time Frame: Up to approximately 7 months (Time of surgery)
pCR rate (ypT0/Tis) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen (independent of lymph node involvement) after completion of neoadjuvant systemic therapy by AJCC staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pCR using the definition of ypT0/Tis will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
Up to approximately 7 months (Time of surgery)
pCR Rate Using the Definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in Participants With a Combined Positive Score [CPS] ≥1
Time Frame: Up to approximately 7 months (Time of surgery)
pCR rates were calculated using the definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 after completion of neoadjuvant systemic therapy by AJCC staging criteria (8th edition) assessed by the local pathologist at the time of surgery. The percentage of participants with a pCR using the three definitions of ypT0/Tis ypN0, ypT0/Tis, and ypT0 ypN0 in participants with a CPS ≥1 (with a positive Programmed Cell Death-Ligand 1 [PD-L1] tumor status) will be presented for pembrolizumab versus placebo, both in combination with the protocol-specified neoadjuvant anticancer therapies.
Up to approximately 7 months (Time of surgery)
EFS in Participants With a CPS ≥1
Time Frame: Up to approximately 12 years
EFS is defined as the time from randomization to disease progression that: precludes surgery, results in a local or distant recurrence, results in a second primary malignancy, or death due to any cause whichever occurs first. The EFS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies, as determined by the investigator for participants with a CPS ≥1 will be presented.
Up to approximately 12 years
OS in Participants With a CPS ≥1
Time Frame: Up to approximately 12 years
OS is defined as the time from date of randomization to date of death due to any cause. The OS following administration of pembrolizumab and placebo, both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies for participants with a CPS ≥1 will be presented.
Up to approximately 12 years
Number of Participants Experiencing an Adverse Event (AE)
Time Frame: Up to approximately 15 months
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE while receiving pembrolizumab or placebo (including 1 month of safety follow up) will be presented.
Up to approximately 15 months
Number of Participants Experiencing a Serious Adverse Event (SAE)
Time Frame: Up to approximately 17 months
An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, Is life-threatening, Requires inpatient hospitalization or prolongation of existing hospitalization, Results in persistent or significant disability/incapacity or Is a congenital anomaly/birth defect. The number of participants who experience an SAE while receiving pembrolizumab or placebo (including 3 months of safety follow up) will be presented.
Up to approximately 17 months
Number of Participants Experiencing an Immune-related AE (irAE)
Time Frame: Up to approximately 15 months
Some AEs that may occur in this study that are known to be related to pembrolizumab immunotherapy treatment and may include: pneumonitis, diarrhea/colitis, aspartate aminotransferase/alanine aminotransferase (AST/ALT) elevation or increased bilirubin, Type 1 diabetes mellitus or hyperglycemia, hypophysitis, hyperthyroidism, hypothyroidism, nephritis and renal dysfunction, and myocarditis. The number of participants who experience an irAE while receiving pembrolizumab or placebo (including 1 month of safety follow up) will be presented.
Up to approximately 15 months
Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Questionnaire Core 30 (QLQ-C30) Score
Time Frame: Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days.
The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Individual responses for each of 28 items are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome, and responses for each of 2 items (overall health and overall quality of life) are given on a 7-point scale (1=Very poor to 7=Excellent), with a higher score indicating a better outcome. The change from Baseline to end of treatment (up to Cycle 4 Day 1) in EORTC-QLQ-C30 scores for participants will be presented.
Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days.
Change from Baseline in EORTC Breast Cancer-Specific QoL Questionnaire (QLQ-BR23) Score
Time Frame: Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days.
The EORTC QLQ-BR23 is a 23-item questionnaire developed to assess the quality of life in women with breast cancer. Responses for each item are given on a 4-point scale (1=Not at All to 4=Very Much), with a lower score indicating a better outcome. The change from Baseline to end of treatment (up to Cycle 4 Day 1) in EORTC QLQ-BR23 score for participants will be presented.
Baseline (Cycle 1 Day 1 in Treatment 1) and Cycles 1 and 4 Day 1 in Treatment 2 (Up to approximately 5 months) Each cycle is 21 days.
Number of Participants who Discontinued Study Treatment Due to an AE
Time Frame: Up to approximately 14 months
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment (pembrolizumab or placebo) due to an AE will be presented.
Up to approximately 14 months

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)

December 27, 2018

Primary Completion (Estimated)

January 24, 2031

Study Completion (Estimated)

January 24, 2031

Study Registration Dates

First Submitted

October 29, 2018

First Submitted That Met QC Criteria

October 29, 2018

First Posted (Actual)

October 30, 2018

Study Record Updates

Last Update Posted (Actual)

July 11, 2025

Last Update Submitted That Met QC Criteria

July 8, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3475-756
  • MK-3475-756 (Other Identifier: MSD)
  • 194604 (Registry Identifier: Japic-CTI)
  • KEYNOTE-756 (Other Identifier: MSD)
  • 2017-004869-27 (EudraCT Number)
  • jRCT2080224535 (Other Identifier: jRCT)
  • 2023-506921-12-00 (Registry Identifier: EU CT)
  • U1111-1294-6352 (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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