Triple Negative Breast NeoplasmsPhase 3NCT03036488
Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy in Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-522/KEYNOTE-522)
A Phase 3 study testing Pembrolizumab, Carboplatin and Paclitaxel in people with Triple Negative Breast Neoplasms, run by Merck Sharp & Dohme LLC at 193 sites in 21 countries.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Triple Negative Breast Neoplasms
- What is being tested?
- Pembrolizumab, Carboplatin and Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,174 participants
- Where
- 193 sitesin 21 countries
- Study dates
- 7 Mar 2017to 14 Oct 2025
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has newly diagnosed, locally advanced, centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
- Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as assessed by the investigator based on radiological and/or clinical assessment:
- T1c, N1-N2
- T2, N0-N2
- T3, N0-N2
- T4a-d, N0-N2
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- Provides a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory.
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
- Demonstrates adequate organ function.
- Males and female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and 6 months after the last dose of study treatment for participants who did not.
Who cannot join
- Has a history of invasive malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
- Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
- Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death - ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen-4 [CTLA-4], OX-40, CD137 [tumor necrosis factor receptor superfamily member 9 (TNFRSF9)]) or has previously participated in a pembrolizumab (MK-3475) clinical study.
- Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 4 weeks of the first dose of treatment in this current study.
- Has received a live vaccine within 30 days of the first dose of study treatment.
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
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- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (i.e., dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
- Has a known history of Human Immunodeficiency Virus (HIV).
- Has known active Hepatitis B or Hepatitis C.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has significant cardiovascular disease, such as: history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months OR congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
- Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the study, starting with the screening visit through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and for 6 months after the last dose of study treatment for participants who have not.
- Has a known hypersensitivity to the components of the study treatment or its analogs.
- Has a known history of active tuberculosis (TB, Bacillus Tuberculosis).
Trial locations and contacts
193 sites in 21 countries.
193 sites in 21 countries
United States47 sites
University of Colorado Cancer Center ( Site 0021)
Aurora, Colorado, 80045
Texas Oncology-Austin Central ( Site 8005)
Austin, Texas, 78731
University of Virginia ( Site 0022)
Charlottesville, Virginia, 22903
The University of Chicago Medical Center ( Site 0047)
Chicago, Illinois, 60637-1447
TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0044)
Cincinnati, Ohio, 45220
Oncology Hematology Care, Inc. ( Site 8011)
Cincinnati, Ohio, 45242
Parkland Health and Hospital System ( Site 0093)
Dallas, Texas, 75235
Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8006)
Dallas, Texas, 75246
Simmons Cancer Center ( Site 0094)
Dallas, Texas, 75390-9015
UT Southwestern Medical Center ( Site 0030)
Dallas, Texas, 75390-9179
Henry Ford Hospital ( Site 0003)
Detroit, Michigan, 48202
North Shore University Health System ( Site 0081)
Evanston, Illinois, 60201
Virginia Cancer Specialists, PC ( Site 8009)
Fairfax, Virginia, 22031
Moncrief Cancer Institute ( Site 0092)
Fort Worth, Texas, 76104
The West Clinic, P.C. ( Site 0078)
Germantown, Tennessee, 38138
Goshen Center for Cancer Care ( Site 0010)
Goshen, Indiana, 46526
Texas Oncology-Memorial City ( Site 8003)
Houston, Texas, 77024
Houston Methodist Cancer Center ( Site 0013)
Houston, Texas, 77030
University of Iowa Hospital and Clinics ( Site 0038)
Iowa City, Iowa, 52242
Broome Oncology, LLC ( Site 8002)
Johnson City, New York, 13790
Kadlec Clinic Hematology and Oncology ( Site 0087)
Kennewick, Washington, 99336
Cedars Sinai Medical Center ( Site 0091)
Los Angeles, California, 90048
Univ of Miami-Sylvester Comprehensive Cancer Center- Kendall satellite ( Site 0079)
Miami, Florida, 33176
Bon Secours Cancer Institute Medical Oncology at St. Mary's ( Site 0033)
Midlothian, Virginia, 23114
Minnesota Oncology Hematology, PA ( Site 8013)
Minneapolis, Minnesota, 55404
Pacific Cancer Care ( Site 0069)
Monterey, California, 93940
Rutgers Cancer Institute of New Jersey ( Site 0073)
New Brunswick, New Jersey, 08903
Yale University School of Medicine ( Site 0054)
New Haven, Connecticut, 06510
Christiana Hospital ( Site 0029)
Newark, Delaware, 19713
Peninsula Cancer Institute, LLC ( Site 0041)
Newport News, Virginia, 23601
Virginia Oncology Associates ( Site 8000)
Norfolk, Virginia, 23502
Nyack Hospital Infusion Center ( Site 0059)
Nyack, New York, 10960
Magee - Women's Hospital ( Site 0011)
Pittsburgh, Pennsylvania, 15213
Texas Oncology- Plano East ( Site 8010)
Plano, Texas, 75075
Providence Portland Medical Center ( Site 0052)
Portland, Oregon, 97213
Northwest Cancer Specialists, P.C. ( Site 8008)
Portland, Oregon, 97227
Rhode Island Hospital ( Site 0060)
Providence, Rhode Island, 02903
Texas Oncology-San Antonio Northeast ( Site 8012)
San Antonio, Texas, 78217
New England Cancer Specialists ( Site 0005)
Scarborough, Maine, 04074
Virginia G. Piper Cancer Center Pharmacy - Scottsdale Healthcare ( Site 0089)
Scottsdale, Arizona, 85268
Seattle Cancer Care Alliance ( Site 0068)
Seattle, Washington, 98109
Orchard Healthcare Research Inc. ( Site 0049)
Skokie, Illinois, 60077
Medical Oncology Associates (Summit Cancer Centers) ( Site 0014)
Spokane, Washington, 99208
Arizona Oncology Associates PC- HOPE ( Site 8001)
Tucson, Arizona, 85711
Texas Oncology-Tyler ( Site 8007)
Tyler, Texas, 75702
ICRI ( Site 0072)
Whittier, California, 90603
YVMH dba Vrigina Mason Memorial/North Star Lodge Cancer Center ( Site 8004)
Yakima, Washington, 98902
Japan19 sites
Chiba Cancer Center ( Site 2519)
Chiba, 260-8717
Saitama Medical University International Medical Center ( Site 2513)
Hidaka, Saitama, 350-1298
Hiroshima City Hiroshima Citizens Hospital ( Site 2501)
Hiroshima, 730-8518
Tokai University Hospital ( Site 2517)
Isehara, Kanagawa, 259-1193
Social medical corporation Hakuaikai Sagara Hospital ( Site 2508)
Kagoshima, 892-0833
National Cancer Center Hospital East ( Site 2518)
Kashiwa, Chiba, 277-8577
St. Marianna University School of Medicine Hospital ( Site 2516)
Kawasaki, Kanagawa, 216-8511
Saitama Cancer Center ( Site 2510)
Kitaadachi-gun, Saitama, 362-0806
Kumamoto University Hospital ( Site 2515)
Kumamoto, 860-8556
Aichi Cancer Center Hospital ( Site 2502)
Nagoya, Aichi-ken, 464-8681
Hyogo College of Medicine Hospital ( Site 2506)
Nishinomiya, Hyōgo, 663-8501
National Hospital Organization Osaka National Hospital ( Site 2505)
Osaka, 540-0006
National Hospital Organization Hokkaido Cancer Center ( Site 2512)
Sapporo, Hokkaido, 003-0804
Kindai University Hospital ( Site 2507)
Sayama, Osaka, 589-8511
Shizuoka Cancer Center Hospital and Research Institute ( Site 2514)
Sunto-gun, Shizuoka, 411-8777
National Cancer Center Hospital ( Site 2500)
Tokyo, 104-0045
St.Luke's International Hospital ( Site 2511)
Tokyo, 104-8560
Toranomon Hospital ( Site 2503)
Tokyo, 105-8470
The Cancer Institute Hospital of JFCR ( Site 2509)
Tokyo, 135-8550
Turkey (Türkiye)14 sites
Adana Acıbadem Hospital Department of Medical Oncology ( Site 1906)
Adana, 01130
Baskent Unıversity Adana Kısla Hospital ( Site 1903)
Adana, 01250
Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1912)
Ankara, 06100
Abdurrahman Yurtaslan Oncology Training and Research Hospital ( Site 1909)
Ankara, 06200
Ozel Medicana International Ankara Hastanesi ( Site 1915)
Ankara, 06510
Antalya Memorial Hospital Department of Medical Oncology ( Site 1908)
Antalya, 07020
Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1901)
Edirne, 22030
İstanbul University Cerrahpaşa Medical Faculty ( Site 1904)
Istanbul, 34098
Amerikan Hospital Medical ( Site 1902)
Istanbul, 34365
Memorial Sisli Hastanesi ( Site 1913)
Istanbul, 34384
Acibadem Altunizade Hastanesi ( Site 1900)
Istanbul, 34662
Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1905)
Izmir, 35040
Izmir Medical Park Hospital Department of Medical Oncology ( Site 1907)
Izmir, 35575
Samsun Ondokuz Mayıs Universitesi Tıp Fakultesi Hastanesi ( Site 1910)
Samsun, Atakum, 55280
France11 sites
CHU Jean Minjoz ( Site 0917)
Besançon, 25000
Polyclinique Bordeaux Nord Aquitaine ( Site 0911)
Bordeaux, 33077
Centre Francois Baclesse ( Site 0907)
Caen, 14000
Centre Jean Perrin ( Site 0903)
Clermont-Ferrand, 63001
Clinique Victor Hugo ( Site 0901)
Le Mans, 72015
Hopital prive du Confluent ( Site 0902)
Nantes, 44277
Institut Curie ( Site 0909)
Paris, 75005
Hopital Saint Louis ( Site 0908)
Paris, 75010
Hopital Diaconesses Croix Saint Simon ( Site 0905)
Paris, 75020
CHU de la Miletrie Poitiers ( Site 0913)
Poitiers, 86021
Institut Claudius Regaud IUCT Oncopole ( Site 0914)
Toulouse, 31059
Spain10 sites
Hospital del Mar ( Site 1306)
Barcelona, 08003
Instituto Oncologico Baselga.Hospital Quiron. ( Site 1312)
Barcelona, 08023
Hospital General Universitari Vall d Hebron ( Site 1301)
Barcelona, 08035
Hospital Universitario Reina Sofia ( Site 1304)
Córdoba, 14004
ICO L Hospitalet ( Site 1305)
L'Hospitalet de Llobregat, Barcelona, 08908
Hospital Universitario Ramon y Cajal ( Site 1300)
Madrid, 28034
Hospital Quiron de Madrid ( Site 1303)
Pozuelo de Alarcón, Madrid, 28223
Complejo Hospitalario Universitario de Santiago ( Site 1308)
Santiago de Compostela, 15706
Hospital Universitario Virgen del Rocio ( Site 1314)
Seville, 41013
Hospital Clinico Univ de Valencia ( Site 1313)
Valencia, 46011
Brazil9 sites
UOPECCAN - Uniao Oeste Paranaense de Estudos e Combate ao Cancer ( Site 0206)
Cascavel, 85806-300
Universidade de Caxias do Sul ( Site 0201)
Caxias do Sul, 95070-560
Hospital Erasto Gaertner ( Site 0207)
Curitiba, 81520-060
Instituto do Cancer do Ceara ( Site 0205)
Fortaleza, 60430-230
Hospital Araujo Jorge ( Site 0204)
Goiânia, 74605-070
Hospital Nossa Senhora da Conceicao ( Site 0203)
Porto Alegre, Rio Grande do Sul, 91350-200
Hospital Sao Lucas da PUCRS ( Site 0200)
Porto Alegre, 90610-900
Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0208)
São José do Rio Preto, 15090-000
Instituto do Cancer de Sao Paulo - ICESP ( Site 0211)
São Paulo, 01246-000
Germany9 sites
HELIOS Klinikum Berlin-Buch ( Site 1005)
Berlin, 13125
Gynaekologisches Zentrum ( Site 1004)
Bonn, 53111
Universitaetsklinikum Erlangen ( Site 1001)
Erlangen, 91054
Kliniken Essen Mitte ( Site 1012)
Essen, 45136
Universitaetsklinik und Poliklinik Halle/Saale ( Site 1008)
Halle, 06120
Universitaetsklinikum Hamburg-Eppendorf ( Site 1007)
Hamburg, 20246
Klinikum der Universit. Muenchen ( Site 1002)
München, 80337
Caritasklinik St. Theresia ( Site 1011)
Saarbrücken, 66113
Universitaets-Frauenklinik Tuebingen ( Site 1003)
Tübingen, 72076
Poland8 sites
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1708)
Bydgoszcz, 85-796
Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1712)
Bydgoszcz, 85-796
Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1701)
Gdynia, 81-519
Centrum Onkologii Instytut im. Marii Skłodowskiej Curie ( Site 1717)
Gliwice, Silesian Voivodeship, 44-101
Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1719)
Krakow, 31-115
Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1700)
Lublin, 20-090
Mazowiecki Szpital Onkologiczny ( Site 1713)
Wieliszew, Masovian Voivodeship, 05-135
Dolnoslaskie Centrum Onkologii. ( Site 1702)
Wroclaw, 53-413
Australia7 sites
Royal Adelaide Hospital ( Site 2008)
Adelaide, South Australia, 5000
Frankston Hospital ( Site 2010)
Franskton, 3199
Royal Brisbane and Women s Hospital ( Site 2003)
Herston, 4029
Cabrini Health ( Site 2009)
Malvern East, Victoria, 3145
St John of God Subiaco Hospital ( Site 2006)
Perth, 6008
Royal North Shore Hospital ( Site 2000)
Sydney, New South Wales, 2065
Westmead Hospital ( Site 2002)
Sydney, New South Wales, 2145
Canada7 sites
Tom Baker Cancer Centre ( Site 0105)
Calgary, Alberta, T2N 4N2
Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)
Montreal, Quebec, H2X 0C1
Jewish General Hospital ( Site 0101)
Montreal, Quebec, H3T 1E2
The Ottawa Hospital - Cancer Care ( Site 0100)
Ottawa, Ontario, K1H 8L6
CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0104)
Québec, Quebec, G1S 4L8
CIUSSS de l'Estrie-CHUS ( Site 0102)
Sherbrooke, Quebec, J1H 5N4
Princess Margaret Cancer Centre ( Site 0103)
Toronto, Ontario, M5G 2M9
Russia7 sites
Arkhangelsk Clinical Oncological Dispensary ( Site 1810)
Arkhangelsk, 163045
Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1805)
Chelyabinsk, 454087
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1806)
Kazan', 420029
Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 1801)
Moscow, 115478
GBU RO Regional Clinical Oncological Dispensary ( Site 1808)
Ryazan, 390046
Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1803)
Saint Petersburg, 197758
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1804)
Ufa, 450054
United Kingdom7 sites
Colchester General Hospital ( Site 1508)
Colchester, Essex, CO4 5JL
Barts Cancer Institute ( Site 1500)
London, EC1M 6BQ
St George s Hospital ( Site 1516)
London, SW17 0QT
Maidstone Hospital ( Site 1511)
Maidstone, ME16 9QQ
The James Cook University Hospital ( Site 1515)
Middlesbrough, TS4 3BW
Nottingham University Hospitals NHS Trust ( Site 1505)
Nottingham, NG5 1PB
Royal Cornwall Hospitals NHS Trust ( Site 1504)
Truro, TR1 3LJ
Colombia6 sites
Hospital Universitario San Ignacio ( Site 0401)
Bogotá, 110231
Instituto Nacional de Cancerologia [Bogota-Colombia] ( Site 0403)
Bogotá, 110411
Hemato Oncologos S.A. ( Site 0400)
Cali, 760001
Instituto De Cancerologia S.A. ( Site 0406)
Medellín, 050024
Oncomedica S.A. ( Site 0404)
Montería, Departamento de Córdoba, 230002
Oncologos del Occidente S.A. ( Site 0405)
Pereira, Risaralda Department, 661002
Israel6 sites
Assaf Harofeh MC ( Site 1605)
Beer Yaakov-Zerifin, 7030001
Oncology institute ( Site 1601)
Beersheba, 8410101
Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1600)
Jerusalem, 9112001
Rabin-Medical Center ( Site 1604)
Petah Tikva, 4941492
Sheba Medical Center ( Site 1602)
Ramat Gan, 5265601
Sourasky Medical Center ( Site 1603)
Tel Aviv, 6423906
Italy6 sites
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 1103)
Brescia, 25100
Ospedale San Luca, AZIENDA USL2 TOSCANA NORD OVEST ( Site 1105)
Lucca, 55100
Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1101)
Meldola, FC, 47014
Istituto Europeo di Oncologia ( Site 1106)
Milan, 20141
Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1102)
Naples, 80131
Ospedale Civile di Macerata ( Site 1104)
Province of Macerata, 62100
Taiwan6 sites
National Cheng Kung University Hospital ( Site 2305)
Tainan, 704
Taipei Veterans General Hospital ( Site 2302)
Taipei, Beitou, 11217
National Taiwan University Hospital ( Site 2301)
Taipei, 100
MacKay Memorial Hospital ( Site 2303)
Taipei, 105
Koo Foundation Sun Yat-Sen Cancer Center ( Site 2304)
Taipei, 11259
Linkou Chang Gung Memorial Hospital ( Site 2300)
Taoyuan, 333
South Korea4 sites
Seoul National University Hospital ( Site 2101)
Seoul, 03080
Severance Hospital Yonsei University Health System ( Site 2100)
Seoul, 03722
Asan Medical Center ( Site 2102)
Seoul, 05505
Samsung Medical Center ( Site 2103)
Seoul, 06351
Sweden4 sites
Linkopings Universitetssjukhus ( Site 1402)
Linköping, 581 85
Karolinska Universitetssjukhuset Solna ( Site 1404)
Solna, 171 64
Norrlands Universitetssjukhus ( Site 1401)
Umeå, 901 85
Akademiska Sjukhuset ( Site 1403)
Uppsala, 751 85
Portugal3 sites
Fundacao Champalimaud ( Site 2444)
Lisbon, 1400-038
Hospital de Santa Maria, E.P.E. ( Site 2445)
Lisbon, 1600-190
Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2446)
Porto, 4200-072
Ireland2 sites
Bon Secours Hospital ( Site 1551)
Cork, T12 DV56
St Vincents University Hospital ( Site 1550)
Dublin, D04 T6F4
Singapore1 site
National Cancer Centre Singapore ( Site 2600)
Singapore, 169610
About this study
Official title: A Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC)
The purpose of this study is to evaluate the efficacy and safety of pembrolizumab (MK-3475) plus chemotherapy vs placebo plus chemotherapy as neoadjuvant therapy and pembrolizumab vs placebo as adjuvant therapy in participants who have triple negative breast cancer (TNBC).
After a screening phase of approximately 28 days, each participant will receive neoadjuvant study treatment (Pembrolizumab + Chemotherapy OR Placebo + Chemotherapy) based on the randomization schedule for approximately 24 weeks (8 cycles). Each participant will then undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant study treatment. After definitive surgery, each participant will receive adjuvant study treatment (Pembrolizumab OR Placebo) for approximately 27 weeks (9 cycles). Following adjuvant study treatment, each participant will be monitored for safety, survival and disease recurrence.
The primary study hypothesis is that pembrolizumab is superior to placebo, in combination with chemotherapy, as measured by the rate of Pathological Complete Response (pCR) and/or Event-free Survival (EFS), in participants with locally advanced TNBC.
- Conditions
- Triple Negative Breast Neoplasms
- Being tested
- Pembrolizumab, Carboplatin, Paclitaxel, Doxorubicin, Epirubicin
- Keywords
- PD1, PD-1, PDL1, PD-L1
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabBiological
Also called MK-3475, KEYTRUDA®
On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; intravenous (IV) infusion.
CarboplatinDrug
Also called PARAPLATIN®
On Day 1 of Cycles 1-4 of the neoadjuvant phase of the study OR on Days 1, 8, 15 of Cycles 1-4 of the neoadjuvant phase of the study; IV infusion.
PaclitaxelDrug
Also called TAXOL®
On Days 1, 8 and 15 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.
DoxorubicinDrug
Also called ADRIAMYCIN®
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
EpirubicinDrug
Also called ELLENCE®
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.
CyclophosphamideDrug
Also called CYTOXAN®
On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.
PlaceboDrug
normal saline solution or dextrose: On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; IV infusion
Granulocyte colony stimulating factor: Filgrastim or PegfilgrastimBiological
Also called NEUPOGEN®, NEULASTA®
For prevention of neutropenia, filgrastim 5 μg/kg/day via subcutaneous (SC) injection administered per standard of care after chemotherapy OR pegfilgrastim 100 µg/kg (individualized) or 6 mg (general approach) via SC injection administered per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab + Chemotherapy | Experimental | Participants receive 200 mg pembrolizumab every 3 weeks (Q3W) + 80 mg/m^2 paclitaxel weekly + carboplatin (Area Under the Curve [AUC]1.5 weekly or AUC5 Q3W) x 4 cycles, followed by 200 mg pembrolizumab Q3W + (60 mg/m^2 doxorubicin OR 90 mg/m^2 epirubicin) + 600 mg/m^2 cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of 200 mg pembrolizumab Q3W as adjuvant therapy post-surgery. Each cycle is 21 days. Receives: Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Cyclophosphamide; Biological: Granulocyte colony stimulating factor: Filgrastim or Pegfilgrastim |
| Placebo + Chemotherapy | Active comparator | Participants receive placebo (normal saline solution) Q3W + 80 mg/m^2 paclitaxel weekly + carboplatin (AUC1.5 weekly or AUC5 Q3W) x 4 cycles, followed by placebo + (60 mg/m^2 doxorubicin OR 90 mg/m^2 epirubicin) + 600 mg/m^2 cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of placebo Q3W as adjuvant therapy post-surgery. Each cycle is 21 days. Receives: Drug: Carboplatin; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Placebo; Biological: Granulocyte colony stimulating factor: Filgrastim or Pegfilgrastim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 (i.e., no Invasive Residual in Breast or Nodes; Noninvasive Breast Residuals Allowed) as Assessed at the Time of Definitive Surgery in All Participants
pCR rate (ypT0/Tis ypN0) was defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.
Measured: Up to approximately 27-30 weeks
Event-free Survival (EFS) in All Participants
EFS was defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes definitive surgery, local or distant recurrence, second primary malignancy, as assessed by Investigator, or death due to any cause.
Measured: Up to approximately 102 months
Secondary outcomes (14)
Overall Survival (OS) in All Participants
OS was defined as the time from randomization to death due to any cause.
Measured: Up to approximately 102 months
pCR Rate Using an Alternative Definition, ypT0 ypN0 (i.e., no Invasive or Noninvasive Residual in Breast or Nodes) at the Time of Definitive Surgery in All Participants
pCR rate (ypT0 ypN0) was defined as the percentage of participants without residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
Measured: Up to approximately 27-30 weeks
pCR Rate Using an Alternative Definition, ypT0 ypN0 (i.e., no Invasive or Noninvasive Residual in Breast or Nodes) at the Time of Definitive Surgery in Participants With Programmed Death Ligand 1 (PD-L1) Positive Tumors (Combined Positive Score [CPS] ≥ 1)
pCR rate (ypT0 ypN0) was defined as the percentage of participants without residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
Measured: Up to approximately 27-30 weeks
pCR Rate Using the Definition of ypT0/Tis ypN0 (i.e., no Invasive Residual in Breast or Nodes; Noninvasive Breast Residuals Allowed) at the Time of Definitive Surgery in Participants With PD-L1 Positive Tumors (CPS ≥ 1)
pCR rate (ypT0/Tis ypN0) was defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
Measured: Up to approximately 27-30 weeks
EFS in Participants With PD-L1 Positive Tumors (CPS ≥ 1)
EFS was defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes definitive surgery, local or distant recurrence, second primary malignancy, as assessed by Investigator, or death due to any cause.
Measured: Up to approximately 102 months
pCR Rate Using an Alternative Definition, ypT0/Tis (i.e., Absence of Invasive Cancer in the Breast Irrespective of Ductal Carcinoma in Situ or Nodal Involvement) at the Time of Definitive Surgery in All Participants
pCR rate (ypT0/Tis) was defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
Measured: Up to approximately 27-30 weeks
pCR Rate Using an Alternative Definition, ypT0/Tis (i.e., Absence of Invasive Cancer in the Breast Irrespective of Ductal Carcinoma in Situ or Nodal Involvement) at the Time of Definitive Surgery in Participants With PD-L1 Positive Tumors (CPS ≥ 1)
pCR rate (ypT0/Tis) was defined as the percentage of participants without invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement following completion of neoadjuvant systemic therapy by current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
Measured: Up to approximately 27-30 weeks
Overall Survival (OS) in Participants With PD-L1 Positive Tumors (CPS ≥ 1)
OS was defined as the time from randomization to death due to any cause.
Measured: Up to approximately 102 months
Number of Participants Who Experienced an Adverse Event (AE)
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product which does not have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the product or procedure. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product was an AE. The number of participants who experienced an AE was reported. AEs were reported for the neoadjuvant phase, adjuvant phase, and combined phases. Each participant is counted a single time for each applicable adverse event per treatment phase (i.e. Neoadjuvant, Adjuvant, Combined).
Measured: Up to approximately 107 weeks
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product which does not have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the product or procedure. Any worsening (clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that is temporally associated with the use of the Sponsor's product was an AE. The number of participants who discontinued study treatment due to an AE was reported for the neoadjuvant phase, adjuvant phase, and combined phases. Each participant is counted a single time for each applicable event per treatment phase (i.e. Neoadjuvant, Adjuvant, Combined).
Measured: Up to approximately 95 weeks
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score in All Participants
The EORTC QLQ-C30 assesses quality of life in cancer patients and includes 30 questions: 1 global scale; 5 functional scales (physical, role, cognitive, emotional, social); 3 symptom scales (fatigue, nausea, pain); 6 symptoms (dyspnea, appetite loss, insomnia, constipation, diarrhea); \& financial impact. Items are scored on a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scale scores are standardized to 0-100. Higher global and functional scores indicate better functioning, while higher symptom scores indicate worse symptoms. Results were presented separately for the neoadjuvant and adjuvant phases, with side-by-side review of phase-specific outputs. A combined phase analysis was not presented because the phases represent distinct clinical settings with different baselines; the adjuvant population is a subset of the neoadjuvant population; and pooling data would introduce substantial missingness, limiting clinical interpretability of the results.
Measured: Neoadjuvant: Baseline and Week 21; Adjuvant: Baseline and Week 24
Change From Baseline in EORTC QLQ-C30 Score in Participants With PD-L1 Positive Tumors (CPS ≥ 1)
The EORTC QLQ-C30 assesses quality of life in cancer patients and includes 30 questions: 1 global scale; 5 functional scales (physical, role, cognitive, emotional, social); 3 symptom scales (fatigue, nausea, pain); 6 symptoms (dyspnea, appetite loss, insomnia, constipation, diarrhea); \& financial impact. Items are scored on a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scale scores are standardized to 0-100. Higher global and functional scores indicate better functioning, while higher symptom scores indicate worse symptoms. Results were presented separately for the neoadjuvant and adjuvant phases, with side-by-side review of phase-specific outputs. A combined phase analysis was not presented because the phases represent distinct clinical settings with different baselines; the adjuvant population is a subset of the neoadjuvant population; and pooling data would introduce substantial missingness, limiting clinical interpretability of the results.
Measured: Neoadjuvant: Baseline and Week 21; Adjuvant: Baseline and Week 24
Change From Baseline in EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23) Breast Symptoms Score in All Participants
The EORTC QLQ-BR23 is a breast-specific module of the EORTC QLQ. It includes 23 items composed of 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and 4 symptom scales (systemic therapy side effects, breast symptoms, arm symptoms and upset by hair loss). Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much). Scores for each scale are standardized into a range of 0 to 100. A higher score on the symptom scale shows a higher ("worse") level of symptoms. Results were presented separately for the neoadjuvant and adjuvant phases, with side-by-side review of phase-specific outputs. A combined phase analysis was not presented because the phases represent distinct clinical settings with different baselines; the adjuvant population is a subset of the neoadjuvant population; and pooling data would introduce substantial missingness, limiting clinical interpretability of the results.
Measured: Neoadjuvant: Baseline and Week 21; Adjuvant: Baseline and Week 24
Change From Baseline in EORTC QLQ-BR23 Breast Symptoms Score in Participants With PD-L1 Positive Tumors (CPS ≥ 1)
The EORTC QLQ-BR23 is a breast-specific module of the EORTC QLQ. It includes 23 items composed of 4 functional scales (body image, sexual functioning, sexual enjoyment, future perspective) and 4 symptom scales (systemic therapy side effects, breast symptoms, arm symptoms and upset by hair loss). Individual responses are given on a 4-point scale (1=Not at All to 4=Very Much). Scores for each scale are standardized into a range of 0 to 100. A higher score on the symptom scale shows a higher ("worse") level of symptoms. Results were presented separately for the neoadjuvant and adjuvant phases, with side-by-side review of phase-specific outputs. A combined phase analysis was not presented because the phases represent distinct clinical settings with different baselines; the adjuvant population is a subset of the neoadjuvant population; and pooling data would introduce substantial missingness, limiting clinical interpretability of the results.
Measured: Neoadjuvant: Baseline and Week 21; Adjuvant: Baseline and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2017 (estimated)
- Study start7 Mar 2017
- Primary completion14 Oct 2025
- Study completion14 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Triple Negative Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,174 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03036488
- Sponsor's protocol ID
- 3475-522
- Other IDs
- 173567, MK-3475-522, KEYNOTE-522, 2022-501382-49-00, U1111-1280-2361, 2016-004740-11, 2016
- Status last verified
- Oct 2026
- First submitted
- 27 Jan 2017
- Last updated
- 22 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Publications
Schmid P, Cortes J, Dent R, McArthur H, Pusztai L, Kummel S, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Im SA, Untch M, Fasching PA, Mouret-Reynier MA, Foukakis T, Ferreira M, Cardoso F, Zhou X, Karantza V, Tryfonidis K, Aktan G, O'Shaughnessy J; KEYNOTE-522 Investigators. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. N Engl J Med. 2024 Nov 28;391(21):1981-1991. doi: 10.1056/NEJMoa2409932. Epub 2024 Sep 15.
PubMed 39282906Kuemmel S, Fasching PA, Schmid P, Harbeck N, Takahashi M, Untch M, Boileau JF, Cortes J, Dent R, O'Shaughnessy J, Pusztai L, Foukakis T, Park YH, Hui R, Cardoso F, Denkert C, Jia L, Pan W, Karantza V, McArthur H. Surgical Outcomes After Neoadjuvant Pembrolizumab Plus Chemotherapy for Triple-Negative Breast Cancer: Results from the Randomized, Placebo-Controlled Phase 3 KEYNOTE-522 Study. Ann Surg Oncol. 2026 Jun;33(6):5550-5557. doi: 10.1245/s10434-026-19121-2. Epub 2026 Feb 25.
PubMed 41739398Takahashi M, Mukai H, Takano T, Tsugawa K, Inoue K, Itoh M, Watanabe J, Tanabe Y, Yamamoto N, Miyoshi Y, Watanabe K, Mukohara T, Kong Y, Shimura M, Beca F, Schmid P, Iwata H. Pembrolizumab for Early-Stage Triple-Negative Breast Cancer: KEYNOTE-522 Japan Subgroup Analysis. Cancer Sci. 2026 Apr;117(4):1106-1116. doi: 10.1111/cas.70307. Epub 2026 Jan 14.
PubMed 41536071Dent R, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Haiderali A, Jia L, Nguyen AM, Pan W, O'Shaughnessy J, Schmid P. Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study. J Natl Cancer Inst. 2024 Oct 1;116(10):1654-1663. doi: 10.1093/jnci/djae129.
PubMed 38913881Favre-Bulle A, Huang M, Haiderali A, Bhadhuri A. Cost-Effectiveness of Neoadjuvant Pembrolizumab plus Chemotherapy Followed by Adjuvant Pembrolizumab in Patients with High-Risk, Early-Stage, Triple-Negative Breast Cancer in Switzerland. Pharmacoecon Open. 2024 Jan;8(1):91-101. doi: 10.1007/s41669-023-00445-8. Epub 2023 Nov 24.
PubMed 37999854Takahashi M, Cortes J, Dent R, Pusztai L, McArthur H, Kummel S, Denkert C, Park YH, Im SA, Ahn JH, Mukai H, Huang CS, Chen SC, Kim MH, Jia L, Li XT, Tryfonidis K, Karantza V, Iwata H, Schmid P. Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Nov 1;6(11):e2342107. doi: 10.1001/jamanetworkopen.2023.42107.
PubMed 37966841Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Andersen J, Patt D, Danso M, Ferreira M, Mouret-Reynier MA, Im SA, Ahn JH, Gion M, Baron-Hay S, Boileau JF, Ding Y, Tryfonidis K, Aktan G, Karantza V, O'Shaughnessy J; KEYNOTE-522 Investigators. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. N Engl J Med. 2022 Feb 10;386(6):556-567. doi: 10.1056/NEJMoa2112651.
PubMed 35139274Perez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.
PubMed 32450725Schmid P, Cortes J, Pusztai L, McArthur H, Kummel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Foukakis T, Fasching PA, Cardoso F, Untch M, Jia L, Karantza V, Zhao J, Aktan G, Dent R, O'Shaughnessy J; KEYNOTE-522 Investigators. Pembrolizumab for Early Triple-Negative Breast Cancer. N Engl J Med. 2020 Feb 27;382(9):810-821. doi: 10.1056/NEJMoa1910549.
PubMed 32101663