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)

NCT03036488 | Completed Phase 3 DMC FDA Drug

• 7 other identifiers: 3475-522173567MK-3475-522KEYNOTE-5222022-501382-49-00U1111-1280-23612016-004740-11
• Study Type: interventional
• Target: 1,174
• Locations: 21 countries
• Sites: 193

Brief 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). 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

Keywords

PD1; PD-1; PDL1; PD-L1

Outcome Measures

Primary Outcomes (2)

• Pathological complete response (pCR) rate using the definition of ypT0/Tis ypN0 (i.e., no invasive residual in breast or nodes; noninvasive breast residuals allowed) at the time of definitive surgery

  pCR rate (ypT0/Tis ypN0) is defined as the percentage of participants without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.

  Up to approximately 27-30 weeks

• Event-free Survival (EFS) as assessed by Investigator

  EFS is defined as the time from randomization to any of the following events: progression of disease that precludes surgery, local or distant recurrence, second primary malignancy (breast or other cancers) or death due to any cause.

  Up to approximately 8 years

Secondary Outcomes (9)

• 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

  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

  Up to approximately 27-30 weeks

• EFS in participants with tumors expressing PD-L1

  Up to approximately 8 years

• pCR rate using an alternative definition, ypT0/Tis (i.e., absence of invasive cancer in the breast irrespective of ductal carcinoma in situ or nodal involvement) at the time of definitive surgery

  Up to approximately 27-30 weeks

• Overall survival (OS)

  Up to approximately 8 years

Study Arms (2)

Pembrolizumab + Chemotherapy

EXPERIMENTAL

Participants receive pembrolizumab every 3 weeks (Q3W) + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by pembrolizumab Q3W + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of pembrolizumab Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.

Biological: Pembrolizumab; Drug: Carboplatin; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Cyclophosphamide; Biological: Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim

Placebo + Chemotherapy

ACTIVE COMPARATOR

Participants receive placebo (normal saline solution) Q3W + paclitaxel weekly + carboplatin (weekly or Q3W) x 4 cycles, followed by placebo + (doxorubicin OR epirubicin) + cyclophosphamide Q3W x 4 cycles as neoadjuvant therapy prior to surgery; followed by 9 cycles of placebo Q3W as adjuvant therapy post-surgery. Each cycle is 21 days.

Drug: Carboplatin; Drug: Paclitaxel; Drug: Doxorubicin; Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Placebo; Biological: Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim

Interventions

Pembrolizumab BIOLOGICAL

On Day 1 of each cycle in the neoadjuvant and adjuvant phases of the study for a total of 17 cycles; intravenous (IV) infusion.

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + Chemotherapy

Carboplatin DRUG

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.

Also known as: PARAPLATIN®

Pembrolizumab + Chemotherapy; Placebo + Chemotherapy

Paclitaxel DRUG

On Days 1, 8 and 15 of Cycles 1-4 in the neoadjuvant phase of the study; IV infusion.

Also known as: TAXOL®

Pembrolizumab + Chemotherapy; Placebo + Chemotherapy

Doxorubicin DRUG

On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.

Also known as: ADRIAMYCIN®

Pembrolizumab + Chemotherapy; Placebo + Chemotherapy

Epirubicin DRUG

On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV injection.

Also known as: ELLENCE®

Pembrolizumab + Chemotherapy; Placebo + Chemotherapy

Cyclophosphamide DRUG

On Day 1 of Cycles 5-8 of the neoadjuvant phase of the study; IV infusion.

Also known as: CYTOXAN®

Pembrolizumab + Chemotherapy; Placebo + Chemotherapy

Placebo DRUG

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

Placebo + Chemotherapy

Granulocyte colony stimulating factor: Filgrastim or Pegfilgastrim BIOLOGICAL

For prevention of neutropenia, filgrastim 5 μg/kg/day via subcutaneous (SC) injection administered per standard of care after chemotherapy OR pegfilgastrim 100 µg/kg (individualized) or 6 mg (general approach) via SC injection administered per standard of care.

Also known as: NEUPOGEN®, NEULASTA®

Pembrolizumab + Chemotherapy; Placebo + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Has newly diagnosed, locally advanced, centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
• Has previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per current American Joint Committee of Cancer (AJCC) staging criteria for breast cancer as assessed by the investigator based on radiological and/or clinical assessment:
• T1c, N1-N2
• T2, N0-N2
• T3, N0-N2
• T4a-d, N0-N2
• Provides a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory.
• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
• Demonstrates adequate organ function.
• Males and female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 12 months after the last dose of study treatment for participants who have received cyclophosphamide, and 6 months after the last dose of study treatment for participants who did not.

You may not qualify if:

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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (193)

Virginia G. Piper Cancer Center Pharmacy - Scottsdale Healthcare ( Site 0089)

Scottsdale, Arizona, 85268, United States

Location

Arizona Oncology Associates PC- HOPE ( Site 8001)

Tucson, Arizona, 85711, United States

Location

Cedars Sinai Medical Center ( Site 0091)

Los Angeles, California, 90048, United States

Location

Pacific Cancer Care ( Site 0069)

Monterey, California, 93940, United States

Location

ICRI ( Site 0072)

Whittier, California, 90603, United States

Location

University of Colorado Cancer Center ( Site 0021)

Aurora, Colorado, 80045, United States

Location

Yale University School of Medicine ( Site 0054)

New Haven, Connecticut, 06510, United States

Location

Christiana Hospital ( Site 0029)

Newark, Delaware, 19713, United States

Location

Univ of Miami-Sylvester Comprehensive Cancer Center- Kendall satellite ( Site 0079)

Miami, Florida, 33176, United States

Location

The University of Chicago Medical Center ( Site 0047)

Chicago, Illinois, 60637-1447, United States

Location

North Shore University Health System ( Site 0081)

Evanston, Illinois, 60201, United States

Location

Orchard Healthcare Research Inc. ( Site 0049)

Skokie, Illinois, 60077, United States

Location

Goshen Center for Cancer Care ( Site 0010)

Goshen, Indiana, 46526, United States

Location

University of Iowa Hospital and Clinics ( Site 0038)

Iowa City, Iowa, 52242, United States

Location

New England Cancer Specialists ( Site 0005)

Scarborough, Maine, 04074, United States

Location

Henry Ford Hospital ( Site 0003)

Detroit, Michigan, 48202, United States

Location

Minnesota Oncology Hematology, PA ( Site 8013)

Minneapolis, Minnesota, 55404, United States

Location

Rutgers Cancer Institute of New Jersey ( Site 0073)

New Brunswick, New Jersey, 08903, United States

Location

Broome Oncology, LLC ( Site 8002)

Johnson City, New York, 13790, United States

Location

Nyack Hospital Infusion Center ( Site 0059)

Nyack, New York, 10960, United States

Location

TriHealth Cancer Institute-Good Samaritan Hospital ( Site 0044)

Cincinnati, Ohio, 45220, United States

Location

Oncology Hematology Care, Inc. ( Site 8011)

Cincinnati, Ohio, 45242, United States

Location

Providence Portland Medical Center ( Site 0052)

Portland, Oregon, 97213, United States

Location

Northwest Cancer Specialists, P.C. ( Site 8008)

Portland, Oregon, 97227, United States

Location

Magee - Women's Hospital ( Site 0011)

Pittsburgh, Pennsylvania, 15213, United States

Location

Rhode Island Hospital ( Site 0060)

Providence, Rhode Island, 02903, United States

Location

The West Clinic, P.C. ( Site 0078)

Germantown, Tennessee, 38138, United States

Location

Texas Oncology-Austin Central ( Site 8005)

Austin, Texas, 78731, United States

Location

Parkland Health and Hospital System ( Site 0093)

Dallas, Texas, 75235, United States

Location

Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8006)

Dallas, Texas, 75246, United States

Location

Simmons Cancer Center ( Site 0094)

Dallas, Texas, 75390-9015, United States

Location

UT Southwestern Medical Center ( Site 0030)

Dallas, Texas, 75390-9179, United States

Location

Moncrief Cancer Institute ( Site 0092)

Fort Worth, Texas, 76104, United States

Location

Texas Oncology-Memorial City ( Site 8003)

Houston, Texas, 77024, United States

Location

Houston Methodist Cancer Center ( Site 0013)

Houston, Texas, 77030, United States

Location

Texas Oncology- Plano East ( Site 8010)

Plano, Texas, 75075, United States

Location

Texas Oncology-San Antonio Northeast ( Site 8012)

San Antonio, Texas, 78217, United States

Location

Texas Oncology-Tyler ( Site 8007)

Tyler, Texas, 75702, United States

Location

University of Virginia ( Site 0022)

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Specialists, PC ( Site 8009)

Fairfax, Virginia, 22031, United States

Location

Bon Secours Cancer Institute Medical Oncology at St. Mary's ( Site 0033)

Midlothian, Virginia, 23114, United States

Location

Peninsula Cancer Institute, LLC ( Site 0041)

Newport News, Virginia, 23601, United States

Location

Virginia Oncology Associates ( Site 8000)

Norfolk, Virginia, 23502, United States

Location

Kadlec Clinic Hematology and Oncology ( Site 0087)

Kennewick, Washington, 99336, United States

Location

Seattle Cancer Care Alliance ( Site 0068)

Seattle, Washington, 98109, United States

Location

Medical Oncology Associates (Summit Cancer Centers) ( Site 0014)

Spokane, Washington, 99208, United States

Location

YVMH dba Vrigina Mason Memorial/North Star Lodge Cancer Center ( Site 8004)

Yakima, Washington, 98902, United States

Location

Royal North Shore Hospital ( Site 2000)

Sydney, New South Wales, 2065, Australia

Location

Westmead Hospital ( Site 2002)

Sydney, New South Wales, 2145, Australia

Location

Royal Adelaide Hospital ( Site 2008)

Adelaide, South Australia, 5000, Australia

Location

Cabrini Health ( Site 2009)

Malvern East, Victoria, 3145, Australia

Location

Frankston Hospital ( Site 2010)

Franskton, 3199, Australia

Location

Royal Brisbane and Women s Hospital ( Site 2003)

Herston, 4029, Australia

Location

St John of God Subiaco Hospital ( Site 2006)

Perth, 6008, Australia

Location

Hospital Nossa Senhora da Conceicao ( Site 0203)

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

UOPECCAN - Uniao Oeste Paranaense de Estudos e Combate ao Cancer ( Site 0206)

Cascavel, 85806-300, Brazil

Location

Universidade de Caxias do Sul ( Site 0201)

Caxias do Sul, 95070-560, Brazil

Location

Hospital Erasto Gaertner ( Site 0207)

Curitiba, 81520-060, Brazil

Location

Instituto do Cancer do Ceara ( Site 0205)

Fortaleza, 60430-230, Brazil

Location

Hospital Araujo Jorge ( Site 0204)

Goiânia, 74605-070, Brazil

Location

Hospital Sao Lucas da PUCRS ( Site 0200)

Porto Alegre, 90610-900, Brazil

Location

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto ( Site 0208)

São José do Rio Preto, 15090-000, Brazil

Location

Instituto do Cancer de Sao Paulo - ICESP ( Site 0211)

São Paulo, 01246-000, Brazil

Location

Tom Baker Cancer Centre ( Site 0105)

Calgary, Alberta, T2N 4N2, Canada

Location

The Ottawa Hospital - Cancer Care ( Site 0100)

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre ( Site 0103)

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0106)

Montreal, Quebec, H2X 0C1, Canada

Location

Jewish General Hospital ( Site 0101)

Montreal, Quebec, H3T 1E2, Canada

Location

CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0104)

Québec, Quebec, G1S 4L8, Canada

Location

CIUSSS de l'Estrie-CHUS ( Site 0102)

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Oncomedica S.A. ( Site 0404)

Montería, Departamento de Córdoba, 230002, Colombia

Location

Oncologos del Occidente S.A. ( Site 0405)

Pereira, Risaralda Department, 661002, Colombia

Location

Hospital Universitario San Ignacio ( Site 0401)

Bogotá, 110231, Colombia

Location

Instituto Nacional de Cancerologia [Bogota-Colombia] ( Site 0403)

Bogotá, 110411, Colombia

Location

Hemato Oncologos S.A. ( Site 0400)

Cali, 760001, Colombia

Location

Instituto De Cancerologia S.A. ( Site 0406)

Medellín, 050024, Colombia

Location

CHU Jean Minjoz ( Site 0917)

Besançon, 25000, France

Location

Polyclinique Bordeaux Nord Aquitaine ( Site 0911)

Bordeaux, 33077, France

Location

Centre Francois Baclesse ( Site 0907)

Caen, 14000, France

Location

Centre Jean Perrin ( Site 0903)

Clermont-Ferrand, 63001, France

Location

Clinique Victor Hugo ( Site 0901)

Le Mans, 72015, France

Location

Hopital prive du Confluent ( Site 0902)

Nantes, 44277, France

Location

Institut Curie ( Site 0909)

Paris, 75005, France

Location

Hopital Saint Louis ( Site 0908)

Paris, 75010, France

Location

Hopital Diaconesses Croix Saint Simon ( Site 0905)

Paris, 75020, France

Location

CHU de la Miletrie Poitiers ( Site 0913)

Poitiers, 86021, France

Location

Institut Claudius Regaud IUCT Oncopole ( Site 0914)

Toulouse, 31059, France

Location

HELIOS Klinikum Berlin-Buch ( Site 1005)

Berlin, 13125, Germany

Location

Gynaekologisches Zentrum ( Site 1004)

Bonn, 53111, Germany

Location

Universitaetsklinikum Erlangen ( Site 1001)

Erlangen, 91054, Germany

Location

Kliniken Essen Mitte ( Site 1012)

Essen, 45136, Germany

Location

Universitaetsklinik und Poliklinik Halle/Saale ( Site 1008)

Halle, 06120, Germany

Location

Universitaetsklinikum Hamburg-Eppendorf ( Site 1007)

Hamburg, 20246, Germany

Location

Klinikum der Universit. Muenchen ( Site 1002)

München, 80337, Germany

Location

Caritasklinik St. Theresia ( Site 1011)

Saarbrücken, 66113, Germany

Location

Universitaets-Frauenklinik Tuebingen ( Site 1003)

Tübingen, 72076, Germany

Location

Bon Secours Hospital ( Site 1551)

Cork, T12 DV56, Ireland

Location

St Vincents University Hospital ( Site 1550)

Dublin, D04 T6F4, Ireland

Location

Assaf Harofeh MC ( Site 1605)

Beer Yaakov-Zerifin, 7030001, Israel

Location

Oncology institute ( Site 1601)

Beersheba, 8410101, Israel

Location

Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1600)

Jerusalem, 9112001, Israel

Location

Rabin-Medical Center ( Site 1604)

Petah Tikva, 4941492, Israel

Location

Sheba Medical Center ( Site 1602)

Ramat Gan, 5265601, Israel

Location

Sourasky Medical Center ( Site 1603)

Tel Aviv, 6423906, Israel

Location

Istituto Scientifico Romagnolo per Studio e Cura Tumori IRST ( Site 1101)

Meldola, FC, 47014, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia ( Site 1103)

Brescia, 25100, Italy

Location

Ospedale San Luca, AZIENDA USL2 TOSCANA NORD OVEST ( Site 1105)

Lucca, 55100, Italy

Location

Ospedale Civile di Macerata ( Site 1104)

Macerata, 62100, Italy

Location

Istituto Europeo di Oncologia ( Site 1106)

Milan, 20141, Italy

Location

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 1102)

Napoli, 80131, Italy

Location

Aichi Cancer Center Hospital ( Site 2502)

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East ( Site 2518)

Kashiwa, Chiba, 277-8577, Japan

Location

National Hospital Organization Hokkaido Cancer Center ( Site 2512)

Sapporo, Hokkaido, 003-0804, Japan

Location

Hyogo College of Medicine Hospital ( Site 2506)

Nishinomiya, Hyōgo, 663-8501, Japan

Location

Tokai University Hospital ( Site 2517)

Isehara, Kanagawa, 259-1193, Japan

Location

St. Marianna University School of Medicine Hospital ( Site 2516)

Kawasaki, Kanagawa, 216-8511, Japan

Location

Kindai University Hospital ( Site 2507)

Sayama, Osaka, 589-8511, Japan

Location

Saitama Medical University International Medical Center ( Site 2513)

Hidaka, Saitama, 350-1298, Japan

Location

Saitama Cancer Center ( Site 2510)

Kitaadachi-gun, Saitama, 362-0806, Japan

Location

Shizuoka Cancer Center Hospital and Research Institute ( Site 2514)

Sunto-gun, Shizuoka, 411-8777, Japan

Location

Chiba Cancer Center ( Site 2519)

Chiba, 260-8717, Japan

Location

Hiroshima City Hiroshima Citizens Hospital ( Site 2501)

Hiroshima, 730-8518, Japan

Location

Social medical corporation Hakuaikai Sagara Hospital ( Site 2508)

Kagoshima, 892-0833, Japan

Location

Kumamoto University Hospital ( Site 2515)

Kumamoto, 860-8556, Japan

Location

National Hospital Organization Osaka National Hospital ( Site 2505)

Osaka, 540-0006, Japan

Location

National Cancer Center Hospital ( Site 2500)

Tokyo, 104-0045, Japan

Location

St.Luke's International Hospital ( Site 2511)

Tokyo, 104-8560, Japan

Location

Toranomon Hospital ( Site 2503)

Tokyo, 105-8470, Japan

Location

The Cancer Institute Hospital of JFCR ( Site 2509)

Tokyo, 135-8550, Japan

Location

Mazowiecki Szpital Onkologiczny ( Site 1713)

Wieliszew, Masovian Voivodeship, 05-135, Poland

Location

Centrum Onkologii Instytut im. Marii Skłodowskiej Curie ( Site 1717)

Gliwice, Silesian Voivodeship, 44-101, Poland

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1708)

Bydgoszcz, 85-796, Poland

Location

Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1712)

Bydgoszcz, 85-796, Poland

Location

Szpital Morski im. PCK. Szpitale Pomorskie Sp. Z o.o ( Site 1701)

Gdynia, 81-519, Poland

Location

Centrum Onkologii Instytut im. Marii Sklodowskiej Curie ( Site 1719)

Krakow, 31-115, Poland

Location

Centrum Onkologii Ziemi Lubelskiej im. sw. Jana z Dukli ( Site 1700)

Lublin, 20-090, Poland

Location

Dolnoslaskie Centrum Onkologii. ( Site 1702)

Wroclaw, 53-413, Poland

Location

Fundacao Champalimaud ( Site 2444)

Lisbon, 1400-038, Portugal

Location

Hospital de Santa Maria, E.P.E. ( Site 2445)

Lisbon, 1600-190, Portugal

Location

Instituto Portugues de Oncologia Do Porto Francisco Gentil E.P.E. ( Site 2446)

Porto, 4200-072, Portugal

Location

Arkhangelsk Clinical Oncological Dispensary ( Site 1810)

Arkhangelsk, 163045, Russia

Location

Chelyabinsk Regional Clinical Oncological Dispensary ( Site 1805)

Chelyabinsk, 454087, Russia

Location

Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1806)

Kazan', 420029, Russia

Location

Russian Oncological Research Center n.a. N.N.Blokhin of MoH ( Site 1801)

Moscow, 115478, Russia

Location

GBU RO Regional Clinical Oncological Dispensary ( Site 1808)

Ryazan, 390046, Russia

Location

Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1803)

Saint Petersburg, 197758, Russia

Location

Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1804)

Ufa, 450054, Russia

Location

National Cancer Centre Singapore ( Site 2600)

Singapore, 169610, Singapore

Location

Seoul National University Hospital ( Site 2101)

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System ( Site 2100)

Seoul, 03722, South Korea

Location

Asan Medical Center ( Site 2102)

Seoul, 05505, South Korea

Location

Samsung Medical Center ( Site 2103)

Seoul, 06351, South Korea

Location

ICO L Hospitalet ( Site 1305)

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Hospital Quiron de Madrid ( Site 1303)

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital del Mar ( Site 1306)

Barcelona, 08003, Spain

Location

Instituto Oncologico Baselga.Hospital Quiron. ( Site 1312)

Barcelona, 08023, Spain

Location

Hospital General Universitari Vall d Hebron ( Site 1301)

Barcelona, 08035, Spain

Location

Hospital Universitario Reina Sofia ( Site 1304)

Córdoba, 14004, Spain

Location

Hospital Universitario Ramon y Cajal ( Site 1300)

Madrid, 28034, Spain

Location

Complejo Hospitalario Universitario de Santiago ( Site 1308)

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen del Rocio ( Site 1314)

Seville, 41013, Spain

Location

Hospital Clinico Univ de Valencia ( Site 1313)

Valencia, 46011, Spain

Location

Linkopings Universitetssjukhus ( Site 1402)

Linköping, 581 85, Sweden

Location

Karolinska Universitetssjukhuset Solna ( Site 1404)

Solna, 171 64, Sweden

Location

Norrlands Universitetssjukhus ( Site 1401)

Umeå, 901 85, Sweden

Location

Akademiska Sjukhuset ( Site 1403)

Uppsala, 751 85, Sweden

Location

Taipei Veterans General Hospital ( Site 2302)

Taipei, Beitou, 11217, Taiwan

Location

National Cheng Kung University Hospital ( Site 2305)

Tainan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 2301)

Taipei, 100, Taiwan

Location

MacKay Memorial Hospital ( Site 2303)

Taipei, 105, Taiwan

Location

Koo Foundation Sun Yat-Sen Cancer Center ( Site 2304)

Taipei, 11259, Taiwan

Location

Linkou Chang Gung Memorial Hospital ( Site 2300)

Taoyuan District, 333, Taiwan

Location

Samsun Ondokuz Mayıs Universitesi Tıp Fakultesi Hastanesi ( Site 1910)

Samsun, Atakum, 55280, Turkey (Türkiye)

Location

Adana Acıbadem Hospital Department of Medical Oncology ( Site 1906)

Adana, 01130, Turkey (Türkiye)

Location

Baskent Unıversity Adana Kısla Hospital ( Site 1903)

Adana, 01250, Turkey (Türkiye)

Location

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 1912)

Ankara, 06100, Turkey (Türkiye)

Location

Abdurrahman Yurtaslan Oncology Training and Research Hospital ( Site 1909)

Ankara, 06200, Turkey (Türkiye)

Location

Ozel Medicana International Ankara Hastanesi ( Site 1915)

Ankara, 06510, Turkey (Türkiye)

Location

Antalya Memorial Hospital Department of Medical Oncology ( Site 1908)

Antalya, 07020, Turkey (Türkiye)

Location

Trakya University Medical Faculty Balkan Oncology Hospital ( Site 1901)

Edirne, 22030, Turkey (Türkiye)

Location

İstanbul University Cerrahpaşa Medical Faculty ( Site 1904)

Istanbul, 34098, Turkey (Türkiye)

Location

Amerikan Hospital Medical ( Site 1902)

Istanbul, 34365, Turkey (Türkiye)

Location

Memorial Sisli Hastanesi ( Site 1913)

Istanbul, 34384, Turkey (Türkiye)

Location

Acibadem Altunizade Hastanesi ( Site 1900)

Istanbul, 34662, Turkey (Türkiye)

Location

Ege University Medical Faculty Tulay Aktas Oncology Hospital ( Site 1905)

Izmir, 35040, Turkey (Türkiye)

Location

Izmir Medical Park Hospital Department of Medical Oncology ( Site 1907)

Izmir, 35575, Turkey (Türkiye)

Location

Colchester General Hospital ( Site 1508)

Colchester, Essex, CO4 5JL, United Kingdom

Location

Barts Cancer Institute ( Site 1500)

London, EC1M 6BQ, United Kingdom

Location

St George s Hospital ( Site 1516)

London, SW17 0QT, United Kingdom

Location

Maidstone Hospital ( Site 1511)

Maidstone, ME16 9QQ, United Kingdom

Location

The James Cook University Hospital ( Site 1515)

Middlesbrough, TS4 3BW, United Kingdom

Location

Nottingham University Hospitals NHS Trust ( Site 1505)

Nottingham, NG5 1PB, United Kingdom

Location

Royal Cornwall Hospitals NHS Trust ( Site 1504)

Truro, TR1 3LJ, United Kingdom

Location

Related Publications (8)

• 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.

  PMID: 39282906 RESULT

• Takahashi 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 Jan 14. doi: 10.1111/cas.70307. Online ahead of print.

  PMID: 41536071 DERIVED

• Dent 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.

  PMID: 38913881 DERIVED

• Favre-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.

  PMID: 37999854 DERIVED

• Takahashi 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.

  PMID: 37966841 DERIVED

• Schmid 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.

  PMID: 35139274 DERIVED

• Perez-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.

  PMID: 32450725 DERIVED

• Schmid 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.

  PMID: 32101663 DERIVED

Related Links

• Merck Clinical Trial Information
• Plain Language Summary

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

pembrolizumab; Carboplatin; Paclitaxel; Doxorubicin; Epirubicin; Cyclophosphamide; Filgrastim; pegfilgrastim

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 27, 2017
• First Posted: January 30, 2017
• Study Start: March 7, 2017
• Primary Completion: October 14, 2025
• Study Completion: October 14, 2025
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

IL (6); KR (4); RU (7); IE (2); GB (7); IT (6); SG (1); TW (6); PL (8); PT (3); CO (6); ES (10); SE (4); FR (11); CA (7); TU (14); BR (9); AU (7); JP (19); US (47); DE (9)