Study of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy for HR+/HER2- Locally Recurrent Inoperable or Metastatic Breast Cancer (MK-3475-B49/KEYNOTE-B49)

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study of Pembrolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy for the Treatment of Chemotherapy-Candidate Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative (HR+/HER2-) Locally Recurrent Inoperable or Metastatic Breast Cancer (KEYNOTE-B49)

The safety and efficacy of pembrolizumab plus the investigator's choice of chemotherapy will be assessed compared to placebo plus the investigator's choice of chemotherapy in the treatment of chemotherapy-candidate hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) locally recurrent inoperable or metastatic breast cancer.

The primary hypotheses are that the combination of pembrolizumab and chemotherapy is superior to placebo and chemotherapy in regards to Progression-Free Survival (PFS) or overall survival (OS) in participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 and ≥10.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Neoplasms
• Intervention / Treatment: Drug: paclitaxel; Biological: pembrolizumab; Drug: nab-paclitaxel; Drug: liposomal doxorubicin; Drug: capecitabine; Drug: normal saline; Drug: dextrose

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Hospital Italiano de Córdoba ( Site 0409)
  • Cordoba, Argentina, X5008HHW
    • Fundación CEMAIC ( Site 0410)
  • San Juan, Argentina, J5400EBB
    • Instituto San Marcos ( Site 0408)
  • Buenos Aires
    • Berazategui, Buenos Aires, Argentina, 1884
      • Centro de Oncología e Investigación de Buenos Aires ( Site 0400)
    • Ciudad autónoma de Buenos Aires, Buenos Aires, Argentina, 1280
      • Hospital Británico de Buenos Aires-Oncology ( Site 0404)
    • Mar del Plata, Buenos Aires, Argentina, B7600FZO
      • Instituto de Investigaciones Clínicas Mar del Plata ( Site 0412)
  • Caba
    • Buenos Aires, Caba, Argentina, C1118AAT
      • Hospital Aleman-Oncology ( Site 0402)
    • Buenos Aires, Caba, Argentina, C1431FWO
      • Centro de Educación Médica e Investigaciones Clínicas (CEMIC) ( Site 0403)
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • Sanatorio de La Mujer ( Site 0405)
    • Rosario, Santa Fe, Argentina, S2000DSV
      • Sanatorio Parque ( Site 0407)
    • Rosario, Santa Fe, Argentina, S2000KZE
      • Instituto de Oncología de Rosario ( Site 0401)
• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University-MQ Health Clinical Trials Unit ( Site 2102)
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital-Department of Medical Oncology ( Site 2101)
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Frankston Hospital-Oncology and Haematology ( Site 2103)
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Breast Cancer Research Centre-WA ( Site 2104)
• Austria
  • Salzburg, Austria, 5020
    • Uniklinikum Salzburg-Universitätsklinik für Innere Medizin III der PMU mit Hämatologie, internistis
  • Niederosterreich
    • Wiener Neustadt, Niederosterreich, Austria, 2700
      • Landesklinikum Wiener Neustadt-Innere Medizin, Hämatologie und internistische Onkologie ( Site 1604)
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Universität Graz-Innere Medizin Klin. Abt. Onkologie ( Site 1609)
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
      • Medizinische Universitaet Innsbruck ( Site 1602)
  • Wien
    • Vienna, Wien, Austria, 1090
      • Medizinische Universität Wien ( Site 1601)
• Brazil
  • Rio de Janeiro, Brazil, 20560121
    • Instituto Nacional de Câncer - INCA-Pesquisa Clinica HC3 ( Site 0208)
  • Rio de Janeiro, Brazil, 20775-001
    • Instituto de Educação, Pesquisa e Gestão em Saúde ( Site 0202)
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50040-000
      • Hospital de Câncer de Recife ( Site 0211)
  • Rio Grande Do Sul
    • Santa Cruz do Sul, Rio Grande Do Sul, Brazil, 96830-180
      • Instituto de Oncologia Saint Gallen ( Site 0206)
  • Santa Catarina
    • Blumenau, Santa Catarina, Brazil, 89010-340
      • Clínica de Oncologia Reichow ( Site 0210)
    • Florianópolis, Santa Catarina, Brazil, 88020210
      • YNOVA Pesquisa Clínica ( Site 0203)
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Center ( Site 0107)
  • Ontario
    • Toronto, Ontario, Canada, M2K 1E1
      • North York General Hospital ( Site 0108)
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre ( Site 0101)
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital ( Site 0110)
    • Montréal, Quebec, Canada, H2X 3E4
      • Centre Hospitalier de l'Université de Montréal ( Site 0105)
    • Quebec City, Quebec, Canada, G1S 4L8
      • Hopital Du Saint-Sacrement ( Site 0109)
    • Trois-Rivières, Quebec, Canada, G8Z 3R9
      • Centre integre universitaire de sante et de services sociaux de la Mauricie-et-du-centre-du-quebec (
• Chile
  • Araucania
    • Temuco, Araucania, Chile, 4800827
      • Centro Investigación del Cáncer James Lind ( Site 0513)
  • Region M. De Santiago
    • Santiago, Region M. De Santiago, Chile, 7500921
      • FALP ( Site 0501)
    • Santiago, Region M. De Santiago, Chile, 7510032
      • Oncovida ( Site 0514)
    • Santiago, Region M. De Santiago, Chile, 7650018
      • Clínica RedSalud Vitacura ( Site 0515)
    • Santiago, Region M. De Santiago, Chile, 8380455
      • Instituto Nacional del Cancer-CR Investigación ( Site 0511)
    • Santiago, Region M. De Santiago, Chile, 8420383
      • Bradfordhill ( Site 0500)
• China
  • Anhui
    • Hefei, Anhui, China, 230031
      • Anhui Cancer Hospital-medical oncology ( Site 2632)
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital Chinese Academy of Medical Science ( Site 2635)
    • Beijing, Beijing, China, 100142
      • Beijing Cancer hospital-Department of Breast Cancer ( Site 2605)
    • Beijing, Beijing, China, 100730
      • Beijing Peking Union Medical College Hospital-Medical Oncology ( Site 2610)
  • Fujian
    • Xiamen, Fujian, China, 361003
      • The First Affiliated hospital of Xiamen University-Breast Surgery ( Site 2613)
  • Guangdong
    • Foshan, Guangdong, China, 528041
      • The First People's Hospital of Foshan-Oncology Department of Breast Cancer ( Site 2620)
    • Guangzhou, Guangdong, China, 510060
      • SUN YAT-SEN UNIVERSITY CANCER CENTRE-oncology breast ( Site 2616)
    • Guangzhou, Guangdong, China, 510289
      • Sun Yat-sen Memorial Hospital, Sun Yat-sen University-Breast Oncology Center ( Site 2641)
    • Shenzhen, Guangdong, China, 518036
      • Peking University Shenzhen Hospital-Oncology Department ( Site 2601)
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Affiliated Tumor Hospital-Oncology Dept. of Breast and Bone Soft Tissue (
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital-Galactophore Department ( Site 2615)
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Wuhan Union Hospital Cancer Center-Cancer Center ( Site 2629)
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital Central South University-Breast department ( Site 2621)
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital ( Site 2608)
  • Jiangsu
    • Nanjing, Jiangsu, China, 210036
      • Jiangsu provincial people's hospital-Oncology Department ( Site 2607)
  • Jiangxi
    • Nanchang, Jiangxi, China, 330009
      • The Third Hospital of Nanchang-Oncology Dept ( Site 2628)
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital-oncology department ( Site 2619)
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • The First Affiliated Hospital of Xian Jiaotong University wa-Oncology ( Site 2604)
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital-Breast surgery ( Site 2623)
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center-Oncology ( Site 2600)
    • Shanghai, Shanghai, China, 200120
      • Renji Hospital Shanghai Jiao Tong University School of Medicine-Breast surgery ( Site 2626)
  • Sichuan
    • Cheng Du, Sichuan, China, 610041
      • West China Hospital Sichuan University-Head and Neck Oncology ( Site 2630)
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital-Department of Breast Cancer ( Site 2612)
  • Xinjiang
    • Urumqi, Xinjiang, China, 830000
      • Xinjiang Medical University Cancer Hospital - Urumqi-galactophore department ( Site 2624)
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital-Breast Oncology ( Site 2622)
    • Linhai, Zhejiang, China, 317000
      • Taizhou Hospital of Zhejiang Province ( Site 2636)
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University-Thyroid and breast surgery ( Site 2625)
• Colombia
  • Antioquia
    • Medellín, Antioquia, Colombia, 050021435
      • Fundación Colombiana de Cancerología Clínica Vida ( Site 0605)
    • Medellín, Antioquia, Colombia, 050024
      • Instituto de Cancerología-Oncology ( Site 0606)
  • Atlantico
    • Barranquilla, Atlantico, Colombia, 080020
      • Clinica de la Costa S.A.S. ( Site 0601)
  • Cesar
    • Valledupar, Cesar, Colombia, 200001
      • Sociedad De Oncologia Y Hematologia Del Cesar-Oncology ( Site 0603)
  • Cordoba
    • Montería, Cordoba, Colombia, 230002
      • Oncomedica S.A.-Oncomedica S.A ( Site 0604)
  • Distrito Capital De Bogota
    • Bogota, Distrito Capital De Bogota, Colombia, 111321
      • Clinica Colsanitas S.A, Sede Clínica Universitaria Colombia ( Site 0607)
• France
  • Paris, France, 75248
    • Institut Curie ( Site 0900)
  • Bouches-du-Rhone
    • Marseille, Bouches-du-Rhone, France, 13009
      • Institut Paoli-Calmettes ( Site 0913)
  • Calvados
    • Caen, Calvados, France, 14076
      • Centre François Baclesse ( Site 0920)
  • Franche-Comte
    • Besançon, Franche-Comte, France, 25000
      • CHU Besançon ( Site 0918)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • Institut Claudius Regaud ( Site 0902)
  • Ile-de-France
    • Villejuif, Ile-de-France, France, 94805
      • Gustave Roussy ( Site 0914)
  • Languedoc-Roussillon
    • Montpellier, Languedoc-Roussillon, France, 34070
      • Centre de Cancérologie du Grand Montpellier ( Site 0912)
  • Loire-Atlantique
    • Saint Herblain, Loire-Atlantique, France, 44805
      • Institut de Cancérologie de l'Ouest ( Site 0907)
  • Maine-et-Loire
    • ANGERS cedex 02, Maine-et-Loire, France, 49055
      • Institut de Cancérologie de l'Ouest ( Site 0915)
  • Nord
    • Lille, Nord, France, 59000
      • Centre Oscar Lambret ( Site 0921)
  • Puy-de-Dome
    • Clermont-Ferrand, Puy-de-Dome, France, 63011
      • Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne ( Site 0901)
  • Rhone-Alpes
    • Lyon, Rhone-Alpes, France, 69008
      • CENTRE LEON BERARD ( Site 0919)
  • Seine-Maritime
    • Rouen, Seine-Maritime, France, 76038
      • Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen ( Site 0904)
  • Vienne
    • Poitiers, Vienne, France, 86021
      • Centre Hospitalier Universitaire de Poitiers-Pôle régional de cancérologie ( Site 0922)
• Germany
  • Berlin, Germany, 10967
    • Vivantes Klinikum Am Urban-Haematologie und Onkologie ( Site 1203)
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Universitaetsklinikum Erlangen-Klinik für Gynäkologie und Geburtshilfe ( Site 1202)
  • Nordrhein-Westfalen
    • Bonn, Nordrhein-Westfalen, Germany, 53111
      • Gynaekologisches Zentrum Bonn ( Site 1201)
    • Düsseldorf, Nordrhein-Westfalen, Germany, 40225
      • Universitaetsklinikum Duesseldorf-Klinik für Frauenheilkunde & Geburtshilfe ( Site 1204)
    • Essen, Nordrhein-Westfalen, Germany, 45136
      • Kliniken Essen-Mitte, Evangelische Huyssens-Stiftung-Klinike für Senologie/ Brustzentrum ( Site 1200
  • Sachsen
    • Dresden, Sachsen, Germany, 01307
      • Universitaetsklinikum Carl Gustav Carus Dresden-Klinik und Poliklinik für Frauenheilkunde und Gebur
• Greece
  • Thessaloniki, Greece, 546 45
    • Euromedica General Clinic Thessaloniki-Oncology Unit ( Site 0301)
  • Attiki
    • Athens, Attiki, Greece, 115 26
      • General Hospital of Athens Laiko-First Department of Internal Medicine ( Site 0305)
    • Athens, Attiki, Greece, 115 28
      • Alexandra Hospital-ONCOLGOY DEPT. ( Site 0302)
    • Marousi, Attiki, Greece, 151 23
      • Hygeia Hospital-3rd Oncology Department ( Site 0304)
  • Irakleio
    • Heraklion, Irakleio, Greece, 715 00
      • University General Hospital of Heraklion-Internal Medicine-Oncology ( Site 0303)
• Guatemala
  • Guatemala, Guatemala, 01010
    • CELAN,S.A ( Site 0151)
  • Guatemala, Guatemala, 01010
    • Gastrosoluciones ( Site 0156)
  • Guatemala, Guatemala, 01010
    • INTEGRA Cancer Institute ( Site 0155)
  • Quetzaltenango, Guatemala, 09002
    • Centro Medico Integral De Cancerología (CEMIC) ( Site 0154)
• Hungary
  • Bacs-Kiskun
    • Kecskemét, Bacs-Kiskun, Hungary, 6000
      • Bacs-Kiskun Megyei Korhaz-Onkoradiologiai Kozpont ( Site 2804)
  • Baranya
    • Pécs, Baranya, Hungary, 7624
      • Pécsi Tudományegyetem Klinikai Központ-Onkoterápiás Intézet ( Site 2807)
  • Csongrad
    • Szeged, Csongrad, Hungary, 6725
      • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ-Onkoterapias Klinika ( Site 2805)
• Ireland
  • Dublin, Ireland, D08 E9P6
    • St. James's Hospital ( Site 1530)
  • Dublin, Ireland, D4 YN63
    • St. Vincent's University Hospital-Medical Oncology Research Department ( Site 1531)
• Israel
  • Ashdod, Israel, 7747629
    • Assuta Ashdod Medical Center ( Site 1703)
  • Be'er Sheva, Israel, 8400000
    • Soroka Medical Center-Oncology ( Site 1702)
  • Haifa, Israel, 3339419
    • Bnai Zion Medical Center-Oncology ( Site 1704)
  • Ramat Gan, Israel, 5265601
    • Sheba Medical Center-ONCOLOGY ( Site 1700)
  • Tel Aviv, Israel, 6423906
    • Sourasky Medical Center-Oncology ( Site 1701)
• Italy
  • Bari, Italy, 70124
    • Instituto Tumori Giovanni Paolo II-ONCOLOGIA MEDICA ( Site 1112)
  • Catania, Italy, 95126
    • Ospedale Cannizzaro ( Site 1118)
  • Milano, Italy, 20141
    • Istituto Europeo di Oncologia IRCCS-Divisione di Senologia Medica ( Site 1111)
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1116)
  • Padova, Italy, 35128
    • Istituto Oncologico Veneto IRCCS ( Site 1117)
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli-Medical Oncology ( Site 1113)
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Ospedale San Raffaele-Oncologia Medica ( Site 1110)
    • Monza, Lombardia, Italy, 20900
      • Ospedale San Gerardo-ASST Monza-Research Unit Phase 1 ( Site 1115)
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Humanitas-U.O di Oncologia medica ed Ematologia ( Site 1114)
• Japan
  • Chiba, Japan, 260-8677
    • Chiba University Hospital ( Site 2212)
  • Fukuoka, Japan, 811-1395
    • National Hospital Organization Kyushu Cancer Center ( Site 2209)
  • Fukushima, Japan, 960-1295
    • Fukushima Medical University ( Site 2200)
  • Kumamoto, Japan, 860-8556
    • Kumamoto University ( Site 2203)
  • Tokyo, Japan, 104-8560
    • St. Luke's International Hospital ( Site 2207)
  • Tokyo, Japan, 113-8431
    • Juntendo University Hospital ( Site 2210)
  • Hyogo
    • Nishinomiya, Hyogo, Japan, 663-8501
      • Hyogo Medical University Hospital ( Site 2201)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 216-8511
      • St. Marianna University School of Medicine Hospital ( Site 2205)
    • Sagamihara, Kanagawa, Japan, 252-0375
      • Kitasato University Hospital ( Site 2204)
  • Osaka
    • Suita, Osaka, Japan, 565-0871
      • Osaka University Hospital ( Site 2211)
  • Saitama
    • Hidaka-city, Saitama, Japan, 350-1298
      • Saitama Medical University International Medical Center ( Site 2208)
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Tokyo Medical University Hospital ( Site 2206)
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center ( Site 2402)
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital-Internal Medicine ( Site 2403)
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System ( Site 2400)
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center-Division of Hematology/Oncology ( Site 2401)
  • Kyonggi-do
    • Goyang-si, Kyonggi-do, Korea, Republic of, 10408
      • National Cancer Center-Center for Breast Cancer ( Site 2404)
    • Seongnam, Kyonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital ( Site 2406)
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur-Radiotherapy and Oncology ( Site 2506)
  • Kuala Lumpur, Malaysia, 59100
    • Pantai Hospital Kuala Lumpur-Cancer Centre ( Site 2503)
  • Kuala Lumpur
    • Lembah Pantai, Kuala Lumpur, Malaysia, 59100
      • University Malaya Medical Centre ( Site 2505)
  • Pulau Pinang
    • George Town, Pulau Pinang, Malaysia, 10990
      • Hospital Pulau Pinang ( Site 2504)
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Sarawak General Hospital-Radiotherapy Unit ( Site 2501)
• Mexico
  • Chihuahua, Mexico, 31000
    • Centro Estatal de Cancerologia-Investigación ( Site 0256)
  • Oaxaca, Mexico, 68020
    • Centro de Investigacion Clinica de Oaxaca ( Site 0252)
  • Distrito Federal
    • México, Distrito Federal, Mexico, 04739
      • Samadhi Centro Oncológico ( Site 0258)
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44280
      • Hospital Civil Fray Antonio Alcalde-Oncology ( Site 0262)
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
      • Filios Alta Medicina ( Site 0253)
• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525 GA
      • Radboudumc-Medical Oncology ( Site 1360)
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 HX
      • Maastricht UMC+-Medical Oncology ( Site 1353)
  • Noord-Brabant
    • Den Bosch, Noord-Brabant, Netherlands, 5223 GZ
      • Jeroen Bosch Hospital ( Site 1359)
    • Tilburg, Noord-Brabant, Netherlands, 5022 GC
      • Elisabeth-TweeSteden Ziekenhuis-Internal Medicine ( Site 1357)
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066 CX
      • Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 1351)
  • Utrecht
    • Amersfoort, Utrecht, Netherlands, 3813TZ
      • Meander Medisch Centrum ( Site 1358)
  • Zuid-Holland
    • Leiden, Zuid-Holland, Netherlands, 2333 ZA
      • Leids Universitair Medisch Centrum-Medical Oncology ( Site 1356)
    • Leidschendam, Zuid-Holland, Netherlands, 2501 ck
      • Haaglanden MC - locatie Antoniushove-Medical oncology ( Site 1355)
    • Schiedam, Zuid-Holland, Netherlands, 3118JH
      • Franciscus Gasthuis & Vlietland, Locatie Vlietland ( Site 1354)
• Philippines
  • National Capital Region
    • Quezon City, National Capital Region, Philippines, 1500
      • East Avenue Medical Center ( Site 0802)
    • San Juan, National Capital Region, Philippines, 1502
      • CARDINAL SANTOS MEDICAL CENTER-Research Room ( Site 0800)
• Poland
  • Kujawsko-pomorskie
    • Bydgoszcz, Kujawsko-pomorskie, Poland, 85-796
      • Centrum Onkologii im. Prof. Franciszka Lukaszczyka-Ambulatorium Chemioterapii ( Site 1813)
  • Malopolskie
    • Krakow, Malopolskie, Poland, 30-727
      • Pratia MCM Krakow ( Site 1809)
  • Mazowieckie
    • Siedlce, Mazowieckie, Poland, 08-110
      • Mazowiecki Szpital Wojewódzki w Siedlcach-Siedleckie Centrum Onkologii ( Site 1818)
    • Warsaw, Mazowieckie, Poland, 04-125
      • Lux med onkologia sp. z o.o. ( Site 1808)
    • Warszawa, Mazowieckie, Poland, 01-748
      • Luxmed Onkologia sp. z o. o. ( Site 1820)
    • Warszawa, Mazowieckie, Poland, 02-781
      • Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Klinika Nowotworów Piersi i Chirurgii (
    • Warszawa, Mazowieckie, Poland, 04-141
      • Wojskowy Instytut Medyczny-Klinika Onkologii ( Site 1803)
    • Wieliszew, Mazowieckie, Poland, 05-135
      • Mazowiecki Szpital Onkologiczny-BREAST CANCER ( Site 1821)
  • Podkarpackie
    • Przemysl, Podkarpackie, Poland, 37-700
      • Wojewodzki Szpital im. Sw. Ojca Pio w Przemyslu ( Site 1819)
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-027
      • Bialostockie Centrum Onkologii-Oddzial Onkologii Klinicznej ( Site 1812)
  • Slaskie
    • Gliwice, Slaskie, Poland, 44-101
      • Narodowy Instytut Onkologii - Oddzial w Gliwicach-Breast Unit ( Site 1811)
  • Zachodniopomorskie
    • Koszalin, Zachodniopomorskie, Poland, 75-581
      • Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie-Oddzial Dzienny Chemioterapii ( Site 1815)
• Portugal
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto - Hospital de Santo António-Oncology Service ( Site 1003)
  • Porto, Portugal, 4200-072
    • Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 1005)
  • Lisboa
    • Lisbon, Lisboa, Portugal, 1400-038
      • Champalimaud Foundation ( Site 1006)
    • Lisbon, Lisboa, Portugal, 1649-035
      • Centro Hospitalar Universitário Lisboa Norte, E.P.E. - Hospital de Santa Maria ( Site 1004)
  • Porto
    • Matosinhos, Porto, Portugal, 4464-513
      • UNIDADE LOCAL DE SAUDE DE MATOSINHOS ( Site 1007)
• Romania
  • Suceava, Romania, 720214
    • Sigmedical Services SRL ( Site 2904)
  • Cluj
    • Cluj-Napoca, Cluj, Romania, 400015
      • Cardiomed SRL Cluj-Napoca ( Site 2902)
    • Cluj-Napoca, Cluj, Romania, 400015
      • Institutul Oncologic-Day Hospital Unit ( Site 2905)
  • Dolj
    • Craiova, Dolj, Romania, 200542
      • Centrul de Oncologie "Sfântul Nectarie"-Medical Oncology ( Site 2901)
  • Maramures
    • Baia Mare, Maramures, Romania, 430291
      • Oncopremium Team-Oncology ( Site 2903)
• Russian Federation
  • Arkhangel Skaya Oblast
    • Arkhangelsk, Arkhangel Skaya Oblast, Russian Federation, 163045
      • Arkhangelsk Clinical Oncological Dispensary-Chemotherapy department ( Site 1902)
  • Moskovskaya Oblast
    • Podolsk, Moskovskaya Oblast, Russian Federation, 142110
      • Podolsk Regional Clinical Hospital ( Site 1907)
  • Moskva
    • Moscow, Moskva, Russian Federation, 111123
      • Moscow Clinical Research Center-Chemotherapy department ( Site 1903)
    • Moscow, Moskva, Russian Federation, 115478
      • Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 1901)
    • Moscow, Moskva, Russian Federation, 121359
      • Central Clinical Hospital of the Presidential Administrative Department ( Site 1904)
  • Nizhegorodskaya Oblast
    • Nizhniy Novgorod, Nizhegorodskaya Oblast, Russian Federation, 603081
      • Nizhegorodsky Regional Oncology Dispensary-chemotherapy ( Site 1912)
  • Ryazanskaya Oblast
    • Ryazan, Ryazanskaya Oblast, Russian Federation, 390046
      • Ryazan Regional Clinical Oncology Center-Oncology #1 ( Site 1906)
  • Sankt-Peterburg
    • Saint Petersburg, Sankt-Peterburg, Russian Federation, 197758
      • N.N.Petrov Research Institute of Oncology ( Site 1900)
    • St. Petersburg, Sankt-Peterburg, Russian Federation, 194017
      • St. Petersburg Clinical Hospital of Russian Academy Of Sciences-Medical Oncology ( Site 1905)
• Spain
  • Cataluna
    • Barcelona, Cataluna, Spain, 08023
      • Hospital Quiron Barcelona ( Site 1326)
  • Madrid
    • Pozuelo de Alarcon, Madrid, Spain, 28223
      • HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID-ONCOLOGIA MEDICA ( Site 1323)
  • Madrid, Comunidad De
    • Madrid, Madrid, Comunidad De, Spain, 28007
      • HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1333)
    • Madrid, Madrid, Comunidad De, Spain, 28034
      • Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 1320)
  • Valenciana, Comunitat
    • Valencia, Valenciana, Comunitat, Spain, 46009
      • Fundación Instituto Valenciano de Oncología-Oncologico ( Site 1332)
• Sweden
  • Stockholms Lan
    • Stockholm, Stockholms Lan, Sweden, 171 76
      • Karolinska Universitetssjukhuset Solna-Tema Cancer - ME Bröst- endokrina tumörer och sarkom ( Site 1
  • Vastra Gotalands Lan
    • Borås, Vastra Gotalands Lan, Sweden, 501 82
      • Södra Älvsborg Sjukhus ( Site 1406)
• Turkey
  • Adana, Turkey, 01250
    • Baskent University Dr. Turgut Noyan Research and Training Center ( Site 2013)
  • Ankara, Turkey, 06230
    • Hacettepe Universitesi-oncology hospital ( Site 2000)
  • Ankara, Turkey, 06520
    • Memorial Ankara Hastanesi-Medical Oncology ( Site 2002)
  • Ankara, Turkey, 06560
    • Gazi Universitesi-Oncology ( Site 2010)
  • Ankara, Turkey, 06800
    • ANKARA ŞEHİR HASTANESİ-Medical Oncology ( Site 2014)
  • Antalya, Turkey, 07059
    • Akdeniz Universitesi Hastanesi-Medical Oncology ( Site 2009)
  • Istanbul, Turkey, 34668
    • Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 2012)
  • Istanbul, Turkey, 34722
    • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 2005)
  • Malatya, Turkey, 44280
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi Eğitim ve Araştırma Hastanesi-Medical Oncology Department
  • Izmir
    • Bornova, Izmir, Turkey, 35100
      • Ege University Medicine of Faculty ( Site 2004)
    • Izmir, Karsiyaka, Izmir, Turkey, 009035575
      • I.E.U. Medical Point Hastanesi-Oncology ( Site 2016)
• United Kingdom
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • The Royal Cornwall Hospital ( Site 1507)
  • England
    • Leicester, England, United Kingdom
      • Leicester Royal Infirmary-HOPE Clinical Trials Unit ( Site 1502)
    • London, England, United Kingdom, EC1A 7BE
      • St Bartholomew's Hospital ( Site 1508)
    • Manchester, England, United Kingdom, M20 4BX
      • The Christie ( Site 1510)
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY38NR
      • Blackpool Victoria Hospital ( Site 1503)
  • London, City Of
    • London, London, City Of, United Kingdom, SE1 9RT
      • Guy's & St Thomas' NHS Foundation Trust ( Site 1501)
    • Londonderry, London, City Of, United Kingdom, BT47 6SB
      • North West Cancer Centre ( Site 1511)
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham-Medicine ( Site 0065)
  • Arizona
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates-Arizona Oncology ( Site 0049)
  • California
    • Monterey, California, United States, 93940
      • Pacific Cancer Care ( Site 0023)
    • San Francisco, California, United States, 94158
      • UCSF Medical Center at Mission Bay ( Site 0043)
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center-Department of Medicine and Oncology ( Site 0026)
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center ( Site 0063)
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist MD Anderson Cancer Center ( Site 0013)
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc. ( Site 0070)
    • Plantation, Florida, United States, 33324
      • Miami Cancer Institute - Plantation ( Site 0076)
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center, LLC ( Site 0032)
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0028)
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago ( Site 0061)
    • Elmhurst, Illinois, United States, 60126
      • Edward-Elmhurst Healthcare, Elmhurst Hospital-Nancy W. Knowles Cancer Center ( Site 0067)
    • Naperville, Illinois, United States, 60540
      • Edward-Elmhurst Healthcare, Edward Hospital-Edward Cancer Center ( Site 0066)
    • Plainfield, Illinois, United States, 60585
      • Edward-Elmhurst Healthcare, Edward Hospital - Plainfield-Edward Cancer Center - Plainfield ( Site 00
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research Inc. ( Site 0037)
  • Indiana
    • Fort Wayne, Indiana, United States, 46845
      • Parkview Research Center at Parkview Regional Medical Center ( Site 0071)
  • Iowa
    • Ames, Iowa, United States, 50010-3014
      • McFarland Clinic, PC ( Site 0041)
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University Health Sciences Shreveport ( Site 0072)
    • Shreveport, Louisiana, United States, 71105
      • CHRISTUS Highland-Oncology Research ( Site 0073)
  • Maine
    • Scarborough, Maine, United States, 04074
      • New England Cancer Specialists ( Site 0007)
  • Maryland
    • Baltimore, Maryland, United States, 21204
      • Greater Baltimore Medical Center-Medical Oncology/Hematology ( Site 0062)
    • Baltimore, Maryland, United States, 21237
      • MFSMC-HJWCI ( Site 0064)
    • Baltimore, Maryland, United States, 21239
      • MedStar Good Samaritan Hospital-Oncology Research ( Site 0069)
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Medical School-Division of Hematology/Oncology ( Site 0052)
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital ( Site 0003)
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0009)
  • New York
    • Johnson City, New York, United States, 13790
      • Broome Oncology ( Site 0018)
    • Nyack, New York, United States, 10960
      • Hematology Oncology Associates of Rockland ( Site 0044)
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hematology Oncology ( Site 0015)
  • North Dakota
    • Fargo, North Dakota, United States, 58102
      • Sanford Fargo Medical Center ( Site 0040)
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center ( Site 0038)
    • Portland, Oregon, United States, 97239-3011
      • Oregon Health and Science University ( Site 0031)
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • St Francis Cancer Center ( Site 0058)
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Sanford Cancer Center ( Site 0021)
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center ( Site 0039)
  • Virginia
    • Midlothian, Virginia, United States, 23114
      • Bon Secours St. Francis Medical Center-Oncology Research ( Site 0020)
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology ( Site 0055)
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates, PS ( Site 0010)
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC ( Site 0008)
    • Yakima, Washington, United States, 98902
      • North Star Lodge ( Site 0035)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

• Has locally recurrent inoperable or metastatic HR+/HER2- breast cancer, which has not been previously treated with cytotoxic chemotherapy in the noncurative setting
• Has progressed on prior endocrine therapy and is now a chemotherapy candidate, meeting the characteristics in regard to previous treatments of one of the following 4 groups:
• Group 1: Has progressed on 2 or more lines of endocrine therapy for advanced/metastatic HR+/HER2-disease, with at least given in combination with a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor. Prior treatment with mTOR and/or PI3-K inhibitors is allowed. OR
• GROUP 2a: Has progressed on 1 line of previous endocrine therapy for advanced/metastatic disease AND had a disease recurrence within 24 months of definitive surgery for the primary tumor and while on adjuvant endocrine therapy. Prior use of CDK4/6 inhibitors is required, either in the adjuvant and/or metastatic setting. Prior treatment with mTOR and/or PI3-K inhibitors is allowed. OR
• GROUP 2b: Has progressed within 12 months of starting 1 line of endocrine therapy with a CDK4/6 inhibitor for advanced/metastatic HR+/HER2- disease. OR
• GROUP 3: If no prior treatment with a CDK4/6 inhibitor, for advanced/metastatic disease and/or early stage disease (adjuvant), participants must have progressed within 6 months of starting 1 line of endocrine therapy with or without an mTOR or PI3-K inhibitor for metastatic disease AND had a relapse within 24 months of definitive surgery for primary tumor and while receiving adjuvant endocrine therapy.
• Has presented a documented radiographic disease progression (as assessed by the investigator and/or histology [biopsy or cytology] for participants presenting with new metastatic lesions) during or after the last administered endocrine therapy prior to entering the study.
• Is a chemotherapy candidate that meets the criteria specified in the protocol
• Provides a new or the last obtained core biopsy, preferably consisting of multiple cores, taken from a locally recurrent or a distant (metastatic) lesion not previously irradiated
• Has centrally confirmed PD-L1 CPS ≥1 and HR+ (estrogen receptor [ER] and/or progesterone receptor [PgR]) /HER2- breast cancer as defined by the most recent American Society of Clinical Oncology (ASCO)/(College of American Pathologists) CAP guidelines on most recent tumor biopsy
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 7 days prior to the first dose of study treatment
• Has adequate organ function within 10 days prior to the start of study
• Male participants must agree to the following during the treatment period and for at least 6 months after the last dose of chemotherapy: refrain from donating sperm PLUS either be abstinent from heterosexual intercourse as their preferred and usual lifestyle or use contraception and agree to use a male condom plus partner use of an additional contraceptive
• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a highly-effective contraceptive method during the treatment period and for at least 120 days after the last dose of pembrolizumab and 180 days after the last dose of chemotherapy (whichever occurs last), AND agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period
• A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention
• Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiologist
• If receiving bisphosphonates or RANK ligand inhibitors, with stable doses for ≥4 weeks prior to the date of randomization, the participant may continue receiving this therapy during the study treatment. If participant needs to initiate these agents during the screening period, a bone scan to evaluate bone disease should be performed prior to randomization.
• Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks prior to the first dose of study intervention and have undetectable HBV viral load prior to randomization
• Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

Exclusion Criteria:

• Has breast cancer amenable to treatment with curative intent
• Has a history or current evidence of any condition (e.g., transfusion-dependent anemia or thrombocytopenia), therapy, or laboratory abnormality that is specifically contraindicated per the current locally-approved labeling, that might confound the results of the study, interfere with the participant's involvement for the full duration of the study, or is not in the best interest of the participant to be involved, in the opinion of the treating investigator
• Has significant cardiac disease, such as: history of myocardial infarction, acute coronary syndrome, coronary angioplasty/stenting/bypass within the last 6 months, congestive heart failure (CHF) New York Heart association (NYHA) Class II-IV, or history of CHF NYHA Class III or IV
• Has advanced/metastatic, symptomatic visceral spread at risk of rapidly evolving into life-threatening complications, such as lymphangitic lung metastases, bone marrow replacement, carcinomatous meningitis, significant symptomatic liver metastases, shortness of breath requiring supplemental oxygen, symptomatic pleural effusion requiring supplemental oxygen, symptomatic pericardial effusion, symptomatic peritoneal carcinomatosis, or the need to achieve rapid symptom control
• Has skin only disease
• Has a known germline BRCA mutation (deleterious or suspected deleterious) and has not received previous treatment with PARP inhibition. either in the adjuvant or metastatic setting (where available and not medically contraindicated). Single-agent PARP inhibitor therapy does not count as a line of endocrine therapy.
• Has received prior chemotherapy for locally recurrent inoperable or metastatic breast cancer
• Has received prior therapy with an anti- programmed cell death 1 (PD-1), anti- programmed cell death ligand 1 (PD-L1), or anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX-40, CD137)
• Has received prior systemic anticancer therapy with other investigational agents within 4 weeks prior to randomization
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.
• Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ excluding cancer in situ of bladder that have undergone potentially curative therapy
• Has known active central nervous system (CNS) metastases
• Has diagnosed carcinomatous meningitis
• Has severe hypersensitivity to pembrolizumab and/or any of its excipients or has any hypersensitivity to the planned chemotherapy agent (paclitaxel, nab-paclitaxel, liposomal doxorubicin, or capecitabine) and/or any of their excipients
• Has an active autoimmune disease that has required systemic treatment in past 2 years
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active infection requiring systemic therapy
• Has a known history of Human Immunodeficiency Virus (HIV) infection
• Has a known COVID-19 infection (symptomatic or asymptomatic)
• Has a known history of active tuberculosis (TB)
• Has a known psychiatric or substance abuse disorder including alcohol or drug dependency that would interfere with the participant's ability to cooperate with the requirements of the study
• Is breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days (or longer as specified by local institutional guidelines) after the last dose of study treatment
• Has had an allogenic tissue/solid organ transplant

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Chemotherapy; Participants receive pembrolizumab 200 mg administered by intravenous infusion (IV) on Day 1 of each 21-day cycle (Q3W) PLUS one of four chemotherapy regimens: 1) paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 of each 28-day cycle (Q4W), 2) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8, and 15 Q4W, 3) liposomal doxorubicin 50 mg/m^2 IV on Day 1 Q4W, OR 4) capecitabine 1000 mg/m^2 by oral administration (PO) twice a day (BID) on Days 1-14 Q3W for up to 35 administrations.	Drug: paclitaxel; IV infusion; Other Names: TAXOL®; Biological: pembrolizumab; Intravenous (IV) infusion; Other Names: MK-3475; KEYTRUDA®; Drug: nab-paclitaxel; IV infusion; Other Names: ABRAXANE®; Drug: liposomal doxorubicin; IV infusion; Other Names: DOXIL®; Drug: capecitabine; oral administration; Other Names: XELODA®
Active Comparator: Placebo + Chemotherapy; Participants receive placebo (normal saline or dextrose) IV on Day 1 Q3W PLUS one of four chemotherapy regimens: 1) paclitaxel 90 mg/m^2 IV on Days 1, 8, and 15 Q4W, 2) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8, and 15 Q4W, 3) liposomal doxorubicin 50 mg/m^2 IV on Day 1 Q4W, OR 4) capecitabine 1000 mg/m^2 PO BID on Days 1-14 Q3W for up to 35 administrations.	Drug: paclitaxel; IV infusion; Other Names: TAXOL®; Drug: nab-paclitaxel; IV infusion; Other Names: ABRAXANE®; Drug: liposomal doxorubicin; IV infusion; Other Names: DOXIL®; Drug: capecitabine; oral administration; Other Names: XELODA®; Drug: normal saline; IV infusion; Drug: dextrose; IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10	PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥10, as assessed by BICR, will be presented.	Up to approximately 33 months
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1	PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥1, as assessed by BICR, will be presented.	Up to approximately 33 months
Overall Survival (OS) in Participants With Combined Positive Score (CPS) ≥10	OS is defined as the time from randomization to death due to any cause. OS for participants with a CPS of ≥10 will be presented.	Up to approximately 75 months
OS in Participants With CPS ≥1	OS is defined as the time from randomization to death due to any cause. OS for participants with a CPS of ≥1 will be presented.	Up to approximately 75 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator in Participants With Combined Positive Score (CPS) ≥10	PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥10, as assessed by investigator, will be presented.	Up to approximately 75 months
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator in Participants With Combined Positive Score (CPS) ≥1	PFS is defined as the time from randomization to the first documented disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. The PFS in participants with a CPS of ≥1, as assessed by investigator, will be presented.	Up to approximately 75 months
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10	ORR is defined as the percentage of participants in the analysis population who achieve confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR for participants with a CPS of ≥10 will be presented.	Up to approximately 75 months
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1	ORR is defined as the percentage of participants in the analysis population who achieve confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR for participants with a CPS of ≥1 will be presented.	Up to approximately 75 months
Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10	DCR is defined as the percentage of participants who achieve Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks. The percentage of participants who experience a confirmed CR, PR, or SD with a CPS of ≥10 will be presented.	Up to approximately 75 months
Disease Control Rate (DCR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1	DCR is defined as the percentage of participants who achieve Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks. The percentage of participants who experience a confirmed CR, PR, or SD with a CPS of ≥1 will be presented.	Up to approximately 75 months
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥10	For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. DOR for participants with a CPS of ≥10 will be presented.	Up to approximately 75 months
Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With Combined Positive Score (CPS) ≥1	For participants who demonstrate CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until disease progression (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. DOR for participants with a CPS of ≥1 will be presented.	Up to approximately 75 months
Change From Baseline in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented in participants with a CPS of ≥10. A higher score indicates a better outcome.	Baseline and up to approximately 75 months
Change From Baseline in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score will be presented in participants with a CPS of ≥1. A higher score indicates a better outcome.	Baseline and up to approximately 75 months
Change From Baseline in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the physical functioning score will be presented in participants with a CPS of ≥10. A higher score indicates a better level of function.	Baseline and up to approximately 75 months
Change From Baseline in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the physical functioning score will be presented in participants with a CPS of ≥1. A higher score indicates a better level of function.	Baseline and up to approximately 75 months
Change From Baseline in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the emotional functioning score will be presented in participants with a CPS of ≥10. A higher score indicates a better level of function.	Baseline and up to approximately 75 months
Change From Baseline in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 4 questions about their emotional functioning (Items 21-24) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the emotional functioning score will be presented in participants with a CPS of ≥1. A higher score indicates a better level of function.	Baseline and up to approximately 75 months
Change From Baseline in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 3 questions about their fatigue (Items 10, 12, 18) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the fatigue score will be presented in participants with a CPS of ≥10. A lower score indicates a better outcome.	Baseline and up to approximately 75 months
Change From Baseline in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 3 questions about their fatigue (Items 10, 12, 18) are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the fatigue score will be presented in participants with a CPS of ≥1. A lower score indicates a better outcome.	Baseline and up to approximately 75 months
Change From Baseline in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for diarrhea (QLQ-C30 Item 17). For this item, individual responses to the question "Have you had diarrhea?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the diarrhea score will be presented in participants with a CPS of ≥10. A lower score indicates a better outcome.	Baseline and up to approximately 75 months
Change From Baseline in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for diarrhea (QLQ-C30 Item 17). For this item, individual responses to the question "Have you had diarrhea?" are given on a 4-point scale (1=Not at all; 4=Very much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the diarrhea score will be presented in participants with a CPS of ≥1. A lower score indicates a better outcome.	Baseline and up to approximately 75 months
Time to Deterioration (TTD) in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in GHS and QoL combined score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Global Health Status/Quality of Life Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) & Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in GHS and QoL combined score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in physical functioning score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Physical Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in physical functioning score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in emotional functioning score (EORTC QLQ-C30 Items 21-24). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in emotional functioning score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Emotional Functioning Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in emotional functioning score (EORTC QLQ-C30 Items 21-24). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in emotional functioning score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in fatigue score (EORTC QLQ-C30 Items 10, 12, 18). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in fatigue score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Fatigue Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in fatigue score (EORTC QLQ-C30 Items 10, 12, 18). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in fatigue score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥10	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in diarrhea score (EORTC QLQ-C30 Item 17). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in diarrhea score, will be presented in participants with a CPS of ≥10. A longer TTD indicates a better outcome.	Up to approximately 75 months
Time to Deterioration (TTD) in Diarrhea Score on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) in Participants with CPS ≥1	TTD is defined as the time to the first onset of a ≥10-point deterioration (decrease) from baseline in diarrhea score (EORTC QLQ-C30 Item 17). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point deterioration (decrease) from baseline in diarrhea score, will be presented in participants with a CPS of ≥1. A longer TTD indicates a better outcome.	Up to approximately 75 months
Percentage of Participants who Experience an Adverse Event (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experience one or more adverse events will be presented.	Up to approximately 75 months
Percentage of Participants who Discontinue Study Drug due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinue study treatment due to an adverse event will be presented.	Up to approximately 75 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2021
• Primary Completion (Estimated): July 21, 2028
• Study Completion (Estimated): July 21, 2028

Study Registration Dates

• First Submitted: May 17, 2021
• First Submitted That Met QC Criteria: May 17, 2021
• First Posted (Actual): May 20, 2021

Study Record Updates

• Last Update Posted (Actual): March 4, 2024
• Last Update Submitted That Met QC Criteria: March 1, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: inoperable; metastatic; programmed cell death receptor 1 (PD-1, PD1); programmed cell death receptor ligand 1 (PD-L1, PDL1); programmed cell death receptor ligand 2 (PD-L2, PDL2); human epidermal growth factor 2 negative (HER2-); hormone receptor positive (HR+); estrogen receptor positive (ER+); progesterone receptor positive (PR+)
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Immune Checkpoint Inhibitors; Paclitaxel; Capecitabine; Pembrolizumab; Albumin-Bound Paclitaxel; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: 3475-B49; MK-3475-B49 (Other Identifier: Merck); KEYNOTE-B49 (Other Identifier: Merck); jRCT2051210049 (Registry Identifier: Japan Registry of Clinical Trials (jRCT)); PHRR210721-003751 (Registry Identifier: Philippine Health Research Registry (PHRR)); 2020-005407-38 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/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