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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03725059
• Other study ID #: 3475-756
• Secondary ID: MK-3475-75619460
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 27, 2018
• Est. completion date: January 24, 2031

Study information

• Verified date: December 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in the treatment of adults who have high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. The primary study hypotheses are: 1) pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pathological Complete Response (pCR) rate defined by the local pathologist, and 2) pembrolizumab is superior to placebo (both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies) as assessed by Event-Free Survival (EFS) as determined by the investigator. The study is considered to have met its primary objective if pembrolizumab is superior to placebo with respect to either pCR (ypT0/Tis ypN0) or EFS.

Description:

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1240
• Est. completion date: January 24, 2031
• Est. primary completion date: January 24, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Has a localized invasive breast ductal adenocarcinoma, confirmed by the local pathologist, that includes either T1c-T2 (tumor size =2 cm), clinical node stage (cN)1-cN2, or T3-T4, cN0-cN2. Note: Inflammatory breast cancer is allowed.
• Has centrally confirmed ER+/HER2-, Grade 3 breast cancer of ductal histology, according to the most recent American Society of Clinical Oncology/College of American Pathologist guidelines.
• Provides a new or recently obtained core needle biopsy, consisting of multiple cores, taken from the primary breast tumor(s) for central determination of HR status (ER and progesterone receptor), HER2, grade, and PD-L1 status. Note: Sponsor agreement is required for formalin-fixed paraffin-embedded (FFPE) tumor tissue sample or slides that were obtained greater than 60 days prior to the date that the documented informed consent was obtained.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to initiation of study treatment.
• Male participants must agree to use contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants must agree to use effective contraception during the treatment period and for at least 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment with pembrolizumab or placebo.
• Has adequate organ function.

Exclusion Criteria:

• Has a history of non-infectious pneumonitis that required treatment with steroids or has current pneumonitis.
• Has breast cancer with lobular histology.
• Has bilateral invasive breast cancer.
• Has metastatic (Stage IV) breast cancer.
• Has multi-centric breast cancer (presence of more than 1 tumor in different quadrants of the breast).
• Has any of the following clinical lymph node staging per current American Joint Committee on Cancer (AJCC) staging criteria for breast cancer staging based on radiological and/or clinical assessment: cN3, cN3a, cN3b, or cN3c.
• Has ER-, progesterone receptor positive breast cancer.
• Has undergone excisional biopsy of the primary tumor and/or axillary lymph nodes or has undergone sentinel lymph node biopsy prior to study treatment.
• Has a known additional, invasive, malignancy that is progressing or required active treatment in the last 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, ductal breast carcinoma in situ, or cervical carcinoma in situ that has undergone potentially curative therapy are not excluded.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs) Note: Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment.
• Has a known history of active tuberculosis (Bacillus tuberculosis).
• Has an active infection requiring systemic therapy.
• Has left ventricular ejection fraction (LVEF) of <50% or below the institution limit of normal, as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
• Has other significant cardiac disease, such as: 1) History of myocardial infarction, acute coronary syndrome, or coronary angioplasty/stenting/bypass within the last 6 months. or 2) Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA Class III or IV.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of hepatitis B or known active hepatitis C virus infection.
• Has received prior treatment for breast cancer.
• Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137).
• Has received a live vaccine within 30 days prior to the first dose of study treatment.
• Has severe hypersensitivity (=Grade 3) to any of the components or excipients used in the study treatments.
• Is/was enrolled in a study of an investigational agent and received study therapy, or used an investigational device within 4 weeks (12 months for an investigational agent or device with anticancer or antiproliferative properties) prior to the first dose of study treatment.
• Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 12 months (for participants who received cyclophosphamide) or 6 months (for participants who did not receive cyclophosphamide) after the last dose of study treatment.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• Pembrolizumab (K)
IV infusion Q3W

Drug:
• Placebo (P)
Normal saline or dextrose IV infusion Q3W
• Paclitaxel (X)
IV infusion QW
• Doxorubicin (A)
IV infusion either in Q2W or Q3W
• Epirubicin (E)
IV infusion either in Q2W or Q3W
• Cyclophosphamide (C)
IV infusion either in Q2W or Q3W
• Endocrine therapy
Variable endocrine therapy for up 10 years

Radiation:
• Radiation therapy
Variable radiation therapy per local standard of care

Procedure:
• Surgery
Surgery for breast cancer

Locations

Country	Name	City	State
Australia	Chris OBrien Lifehouse ( Site 2107)	Camperdown	New South Wales
Australia	Frankston Hospital ( Site 2103)	Frankston	Victoria
Australia	Peter MacCallum Cancer Centre ( Site 2102)	Melbourne	Victoria
Australia	Mater Misericordiae Ltd ( Site 2106)	South Brisbane	Queensland
Australia	Royal North Shore Hospital ( Site 2100)	Sydney	New South Wales
Australia	Westmead Hospital ( Site 2101)	Sydney	New South Wales
Belgium	Institut Jules Bordet ( Site 0710)	Anderlecht	Bruxelles-Capitale, Region De
Belgium	Imelda Ziekenhuis Bonheiden ( Site 0703)	Bonheiden	Antwerpen
Belgium	Cliniques Universitaires Saint-Luc ( Site 0701)	Brussels	Bruxelles-Capitale, Region De
Belgium	UZ Antwerpen - Medical Oncology ( Site 0709)	Edegem	Antwerpen
Belgium	AZ Maria Middelares Gent ( Site 0700)	Gent	Oost-Vlaanderen
Belgium	Jessa Ziekenhuis Campus Virga Jesse ( Site 0704)	Hasselt	Limburg
Belgium	AZ Groeninge ( Site 0705)	Kortrijk	West-Vlaanderen
Belgium	UZ Leuven ( Site 0702)	Leuven	Vlaams-Brabant
Belgium	CHC MontLegia ( Site 0707)	Liège	Liege
Belgium	CHU UCL Namur Site de Godinne ( Site 0706)	Yvoir	Namur
Brazil	CEPON - Centro de Pesquisas Oncologicas ( Site 0208)	Florianopolis	Santa Catarina
Brazil	Hospital Araujo Jorge Associacao de Combate ao Cancer de Goias ( Site 0205)	Goiania	Goias
Brazil	ONCOSITE - Centro de Pesquisa Clinica em Oncologia ( Site 0206)	Ijui	Rio Grande Do Sul
Brazil	Centro de Novos Tratamentos Itajai - Clinica de Neoplasias Litoral ( Site 0207)	Itajai	Santa Catarina
Brazil	Associacao Hospitalar Moinhos de Vento ( Site 0201)	Porto Alegre	Rio Grande Do Sul
Brazil	Uniao Brasileira de Educacao e Assistencia Hospital Sao Lucas da Pucrs ( Site 0202)	Porto Alegre	Rio Grande Do Sul
Brazil	Instituto Nacional de Cancer - INCA HC III ( Site 0200)	Rio de Janeiro
Brazil	Clinica de Pesquisas e Ctro de Estudos Onc. Ginecol. e Mamaria Ltda ( Site 0204)	Sao Paulo
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP ( Site 0209)	Sao Paulo
Brazil	Núcleo de Pesquisa Clínica da Rede São Camilo ( Site 0210)	São Paulo	Sao Paulo
Canada	Cross Cancer Institute ( Site 0115)	Edmonton	Alberta
Canada	CISSS de la Monteregie-Centre ( Site 0108)	Greenfield Park	Quebec
Canada	Centre Hospitalier de l Universite de Montreal - CHUM ( Site 0114)	Montreal	Quebec
Canada	Hopital Maisonneuve-Rosemont CIUSSS de l Est de L Ile de Montreal ( Site 0111)	Montreal	Quebec
Canada	Jewish General Hospital ( Site 0103)	Montreal	Quebec
Canada	CHU de Quebec Universite Laval - Hopital du Saint-Sacrement ( Site 0101)	Quebec
Canada	Princess Margaret Cancer Centre ( Site 0112)	Toronto	Ontario
Canada	Centre Hospitalier Regional de Trois-Rivieres ( Site 0106)	Trois-Rivières	Quebec
Canada	BC Cancer-Vancouver Center ( Site 0116)	Vancouver	British Columbia
China	Cancer Hospital Chinese Academy of Medical Sciences ( Site 3208)	Beijing	Beijing
China	The First Hospital of Jilin University ( Site 3201)	Changchun	Jilin
China	Hunan Cancer Hospital ( Site 3214)	Changsha	Hunan
China	Fujian Medical University Union Hospital-1 Bingfanglou-Oncology ( Site 3207)	Fuzhou Fujian	Fujian
China	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University ( Site 3213)	Guangzhou	Guangdong
China	The First Affiliated Hospital of Zhejiang University ( Site 3203)	Hangzhou	Jiangsu
China	Zhejiang Cancer Hospital.... ( Site 3210)	Hangzhou	Zhejiang
China	Zhejiang Provincial People's Hospital ( Site 3225)	Hangzhou	Zhejiang
China	Harbin Medical University Cancer Hospital ( Site 3200)	Harbin	Heilongjiang
China	Anhui Provincial Hospital ( Site 3224)	Heifei	Anhui
China	Fudan University Shanghai Cancer Center ( Site 3205)	Shanghai	Shanghai
China	Ruijin Hosp,Shanghai Jiao Tong University School of Medicine ( Site 3215)	Shanghai	Anhui
China	Fourth Hospital Of Hebei Medical University ( Site 3216)	Shijia Zhuang	Hebei
China	Tianjin Medical University Cancer Institute & Hospital ( Site 3209)	Tianjin	Tianjin
China	Cancer Hospital Affiliated to Xinjiang Medical University ( Site 3219)	Urumqi	Xinjiang
China	Hubei Cancer Hospital ( Site 3211)	Wuhan	Hubei
China	The First Affiliated Hospital of Xi an Jiaotong University ( Site 3220)	XI An	Shanxi
China	Henan Cancer Hospital ( Site 3212)	Zhengzhou	Henan
Colombia	Clinica de la Costa Ltda. ( Site 0400)	Barranquilla	Atlantico
Colombia	Centro de Investigacion Clinica del Country ( Site 0402)	Bogota	Distrito Capital De Bogota
Colombia	Fundacion Universitaria Sanitas ( Site 0403)	Bogota	Distrito Capital De Bogota
Colombia	Centro Medico Imbanaco de Cali S.A ( Site 0406)	Cali	Valle Del Cauca
Colombia	Clínica Vida Fundación - Sede Poblado ( Site 0405)	Medellin	Antioquia
Colombia	Rodrigo Botero SAS ( Site 0407)	Medellin	Antioquia
Colombia	Oncomedica S.A. ( Site 0401)	Monteria	Cordoba
Costa Rica	Hospital Metropolitano - Sede Lindora ( Site 4203)	Santa Ana	San Jose
France	Institut Sainte Catherine ( Site 0916)	Avignon	Provence-Alpes-Cote-d Azur
France	Centre Francois Baclesse ( Site 0927)	Caen	Calvados
France	Centre Jean Perrin ( Site 0909)	Clermont Ferrand Cedex	Puy-de-Dome
France	Centre Georges Francois Leclerc ( Site 0920)	Dijon	Cote-d Or
France	Clinique Victor Hugo ( Site 0906)	Le Mans	Sarthe
France	Centre Oscar Lambret ( Site 0911)	Lille	Nord-Pas-de-Calais
France	CHR-METZ-THIONVILLE - Hopital de Mercy ( Site 0919)	Metz	Moselle
France	Centre de Cancerologie du Grand Montpellier ( Site 0925)	Montpellier	Herault
France	Hopital Saint-Louis ( Site 0908)	Paris
France	Hopital Tenon ( Site 0914)	Paris
France	Institut Curie ( Site 0900)	Paris
France	Institut Curie - Centre Rene Huguenin ( Site 0917)	Saint-Cloud	Hauts-de-Seine
France	Institut Claudius Regaud IUCT Oncopole ( Site 0903)	Toulouse	Haute-Garonne
France	Institut Gustave Roussy ( Site 0926)	Villejuif	Val-de-Marne
Germany	Gynaekologisches Zentrum ( Site 1003)	Bonn	Nordrhein-Westfalen
Germany	Universitaetsklinikum Carl Gustav Carus ( Site 1008)	Dresden	Sachsen
Germany	Universitaetsklinikum Erlangen ( Site 1001)	Erlangen	Bayern
Germany	Kliniken Essen Mitte Gmbh Evang. Huyssens Stiftung ( Site 1006)	Essen	Nordrhein-Westfalen
Germany	Medizinische Management GmbH ( Site 1012)	Friedrichshafen	Baden-Wurttemberg
Germany	Gynaekologisch-onkologische Praxis Hannover ( Site 1013)	Hannover	Niedersachsen
Germany	Klinikum der Universitaet Muenchen - Grosshadern ( Site 1000)	Muenchen	Bayern
Germany	MVZ Nordhausen gGmbH - Praxis Dr. Grafe ( Site 1005)	Nordhausen	Thuringen
Germany	Sana Klinikum Offenbach GmbH ( Site 1002)	Offenbach	Hessen
Germany	Frauenklinik St. Louise ( Site 1014)	Paderborn	Nordrhein-Westfalen
Germany	Caritas Klinikum Saarbruecken St. Theresia ( Site 1009)	Saarbruecken	Saarland
Germany	HELIOS Dr. Horst Schmidt Kliniken Wiesbaden ( Site 1004)	Wiesbaden	Hessen
Hungary	Orszagos Onkologiai Intezet ( Site 2908)	Budapest
Hungary	Szent Margit Korhaz ( Site 2901)	Budapest
Hungary	Uzsoki Utcai Korhaz ( Site 2902)	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont ( Site 2907)	Debrecen
Hungary	Somogy Megyei Kaposi Mor Oktato Korhaz ( Site 2915)	Kaposvar
Hungary	Bacs-Kiskun Megyei Korhaz ( Site 2913)	Kecskemet	Bacs-Kiskun
Hungary	Borsod-Abauj-Zemplen Megyei Korhaz es Egyetemi OktatoKorhaz ( Site 2904)	Miskolc	Borsod-Abauj-Zemplen
Hungary	Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 2905)	Pecs	Baranya
Ireland	Bon Secours Hospital ( Site 1554)	Cork
Ireland	St. James s Hospital ( Site 1553)	Dublin
Israel	HaEmek Medical Center ( Site 1712)	Afula
Israel	Assuta Ashdod Public ( Site 1704)	Ashdod
Israel	Soroka Medical Center ( Site 1701)	Beer Sheva
Israel	Rambam Health Care Campus-Oncology Division ( Site 1705)	Haifa
Israel	Hadassah Ein Karem - Sharett Institute of Oncology ( Site 1700)	Jerusalem
Israel	Shaare Zedek Medical Center ( Site 1708)	Jerusalem
Israel	Meir Medical Center ( Site 1710)	Kfar-Saba
Israel	Holy Family Hospital ( Site 1711)	Nazareth
Israel	Rabin Medical Center ( Site 1702)	Petah Tikva
Israel	Chaim Sheba Medical Center. ( Site 1707)	Ramat Gan
Israel	Kaplan Medical Center ( Site 1703)	Rehovot
Israel	Assuta Medical Center ( Site 1709)	Tel Aviv
Israel	Sourasky Medical Center ( Site 1706)	Tel Aviv
Japan	Chiba Cancer Center ( Site 2605)	Chiba
Japan	Fukushima Medical University Hospital ( Site 2610)	Fukushima
Japan	Saitama Medical University International Medical Center ( Site 2606)	Hidaka	Saitama
Japan	Hiroshima City Hiroshima Citizens Hospital ( Site 2603)	Hiroshima
Japan	National Cancer Center Hospital East ( Site 2613)	Kashiwa	Chiba
Japan	Saitama Cancer Center ( Site 2612)	Kitaadachi-gun	Saitama
Japan	Kumamoto University Hospital ( Site 2602)	Kumamoto
Japan	Aichi Cancer Center Hospital ( Site 2601)	Nagoya	Aichi
Japan	Hyogo College of Medicine Hospital ( Site 2600)	Nishinomiya	Hyogo
Japan	National Hospital Organization - Osaka National Hospital - Institute For Clinical Research ( Site 26	Osaka
Japan	Kitasato University Hospital ( Site 2616)	Sagamihara	Kanagawa
Japan	National Hospital Organization Hokkaido Cancer Center ( Site 2607)	Sapporo	Hokkaido
Japan	Shizuoka Cancer Center Hospital and Research Institute ( Site 2611)	Sunto-gun	Shizuoka
Japan	Showa University Hospital ( Site 2615)	Tokyo
Japan	The Cancer Institute Hospital of JFCR ( Site 2604)	Tokyo
Japan	Toranomon Hospital ( Site 2608)	Tokyo
Korea, Republic of	National Cancer Center ( Site 2204)	Goyang-si	Kyonggi-do
Korea, Republic of	Samsung Medical Center ( Site 2203)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 2200)	Seoul
Korea, Republic of	Severance Hospital Yonsei University Health System ( Site 2201)	Seoul
Korea, Republic of	Asan Medical Center ( Site 2202)	Songpagu	Seoul
New Zealand	Canterbury Regional Cancer & Blood Services ( Site 2303)	Christchurch	Canterbury
New Zealand	Tauranga Hospital ( Site 2302)	Tauranga	Bay Of Plenty
New Zealand	Capital & Coast District Health Board - Wellington Hospital ( Site 2301)	Wellington
Poland	Bialostockie Centrum Onkologii ( Site 1819)	Bialystok	Podlaskie
Poland	Beskidzkie Centrum Onkologii im. Jana Pawla II ( Site 1810)	Bielsko-Biala	Slaskie
Poland	Centrum Onkologii im. Prof. Franciszka Lukaszczyka ( Site 1800)	Bydgoszcz	Kujawsko-pomorskie
Poland	Wojewodzki Szpital Specjalistyczny nr 4 w Bytomiu ( Site 1807)	Bytom	Slaskie
Poland	Wojewodzkie Centrum Onkologii Copernicus ( Site 1817)	Gdansk	Pomorskie
Poland	Szpitale Pomorskie Sp. z o.o. ( Site 1818)	Gdynia	Pomorskie
Poland	Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 1801)	Gliwice	Slaskie
Poland	Instytut Centrum Zdrowia Matki Polki ( Site 1821)	Lodz	Lodzkie
Poland	Mazowiecki Szpital Specjalistyczny im. dr Jozefa Psarskiego ( Site 1814)	Ostroleka	Mazowieckie
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (	Warszawa	Mazowieckie
Poland	Mazowiecki Szpital Onkologiczny ( Site 1803)	Wieliszew	Mazowieckie
Poland	Dolnoslaskie Centrum Onkologii. ( Site 1820)	Wroclaw	Dolnoslaskie
Portugal	CHLN Hospital Santa Maria ( Site 2501)	Lisboa
Portugal	Fundacao Champalimaud ( Site 2500)	Lisboa	Aveiro
Portugal	Hospital Geral de Santo Antonio ( Site 2503)	Porto
Portugal	Inst. Portugues de Oncologia de Porto Francisco Gentil EPE ( Site 2502)	Porto
Puerto Rico	UPR Comprehensive Cancer Center ( Site 6200)	San Juan
Russian Federation	Arkhangelsk Clinical Oncological Dispensary ( Site 1901)	Arkhangelsk	Arkhangel Skaya Oblast
Russian Federation	Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1903)	Kazan	Tatarstan, Respublika
Russian Federation	Central Clinical Hospital with outpatient Clinic ( Site 1907)	Moscow	Moskva
Russian Federation	Medical Rehabilitation Center ( Site 1912)	Moscow	Moskva
Russian Federation	N.N. Blokhin NMRCO ( Site 1908)	Moscow	Moskva
Russian Federation	Ryazan Regional Clinical Oncology Dispensary ( Site 1910)	Ryazan	Ryazanskaya Oblast
Russian Federation	Railway Hospital of OJSC ( Site 1913)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Scientific Research Oncology Institute n.a. N.N.Petrov ( Site 1900)	Saint Petersburg	Sankt-Peterburg
Russian Federation	Tomsk Scientific Research Institute of Oncology ( Site 1905)	Tomsk	Tomskaya Oblast
Russian Federation	Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1909)	Ufa	Baskortostan, Respublika
Spain	Hospital Teresa Herrera - Chuac ( Site 1358)	A Coruna	La Coruna
Spain	Hospital Clinic I Provincial de Barcelona ( Site 1353)	Barcelona
Spain	Hospital Vall D Hebron ( Site 1357)	Barcelona
Spain	Instituto Oncologico Baselga.Hospital Quiron. ( Site 1352)	Barcelona
Spain	Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1363)	Hospitalet de Llobregat	Barcelona
Spain	Complejo Hospitalario de Jaen ( Site 1364)	Jaen
Spain	Hospital Clinico San Carlos ( Site 1354)	Madrid
Spain	Hospital General Universitario Gregorio Maranon ( Site 1367)	Madrid	Madrid, Comunidad De
Spain	Hospital Ruber Internacional ( Site 1370)	Madrid
Spain	Hospital Universitario 12 de Octubre ( Site 1356)	Madrid
Spain	Hospital Quiron de Madrid ( Site 1351)	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitario Virgen del Rocio ( Site 1360)	Sevilla
Spain	Hospital Clinico Universitario de Valencia ( Site 1355)	Valencia	Valenciana, Comunitat
Spain	Hospital General Arnau de Vilanova de Valencia ( Site 1369)	Valencia
Taiwan	China Medical University Hospital ( Site 2401)	Taichung
Taiwan	National Cheng Kung University Hospital ( Site 2400)	Tainan
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center ( Site 2403)	Taipei
Taiwan	National Taiwan University Hospital ( Site 2404)	Taipei
Taiwan	Linkou Chang Gung Memorial Hospital ( Site 2402)	Taoyuan
Ukraine	Communal nonprofit enterprise "Kherson Regional Oncology Dispensary" of Kherson Regional Council (	Antonivka Village	Khersonska Oblast
Ukraine	Dnipropetrovsk City Multidiscipline Clinical Hosp. 4 of DRC ( Site 2702)	Dnipro	Dnipropetrovska Oblast
Ukraine	MI Precarpathian Clinical Oncology Center ( Site 2707)	Ivano-Frankivsk	Ivano-Frankivska Oblast
Ukraine	Communal non profit enterprise Regional Clinical Oncology Center ( Site 2721)	Kharkiv	Kharkivska Oblast
Ukraine	Khmelnitskiy Regional Onkology Dispensary ( Site 2704)	Khmelnitskiy	Khmelnytska Oblast
Ukraine	MI Kryviy Rih Center of Dnipropetrovsk Regional Council ( Site 2700)	Kryviy Rih	Dnipropetrovska Oblast
Ukraine	Kyiv City Clinical Oncology Centre ( Site 2716)	Kyiv
Ukraine	National Cancer Institute of the MoH of Ukraine ( Site 2719)	Kyiv	Kyivska Oblast
Ukraine	MI Odesa Regional Clinical Hospital ( Site 2701)	Odesa	Odeska Oblast
Ukraine	MI Odessa Regional Oncological Centre ( Site 2714)	Odesa	Odeska Oblast
Ukraine	Medical center of the Limited Liability Company Yulis ( Site 2720)	Zaporizhzhia	Zaporizka Oblast
United Kingdom	University Hospitals Bristol NHS Foundation Trust ( Site 1503)	Bristol	Bristol, City Of
United Kingdom	Colchester General Hospital ( Site 1508)	Colchester	Essex
United Kingdom	Barts Health NHS Trust ( Site 1500)	London	London, City Of
United Kingdom	Guy's Hospital ( Site 1501)	London	London, City Of
United Kingdom	St. Georges University Hospital NHS Foundation Trust ( Site 1505)	London	London, City Of
United Kingdom	Nottingham University Hospitals NHS Trust ( Site 1504)	Nottingham	England
United Kingdom	Birmingham & Solihull Heartlands Hospital NHS ( Site 1506)	Solihull
United Kingdom	Royal Cornwall Hospital ( Site 1502)	Truro
United States	University of Colorado Cancer Center ( Site 0008)	Aurora	Colorado
United States	Texas Oncology-Austin Central ( Site 8004)	Austin	Texas
United States	Maryland Oncology Hematology, P.A. ( Site 8007)	Bethesda	Maryland
United States	St. Vincent Frontier Cancer Center ( Site 0033)	Billings	Montana
United States	Massachusetts General Hospital ( Site 0024)	Boston	Massachusetts
United States	Medical University of South Carolina ( Site 0053)	Charleston	South Carolina
United States	The University of Chicago Medical Center ( Site 0080)	Chicago	Illinois
United States	Texas Oncology-Baylor Charles A. Sammons Cancer Center ( Site 8009)	Dallas	Texas
United States	Texas Oncology-Dallas Presbyterian Hospital ( Site 8002)	Dallas	Texas
United States	MGH - North Shore Cancer Center ( Site 0081)	Danvers	Massachusetts
United States	Geisinger Medical Center ( Site 0052)	Danville	Pennsylvania
United States	Southern Cancer Center, PC ( Site 8003)	Daphne	Alabama
United States	Henry Ford Health System ( Site 0028)	Detroit	Michigan
United States	Cancer Treatment Centers of America at Western Regional Medical Center ( Site 0001)	Goodyear	Arizona
United States	Goshen Center for Cancer Care ( Site 0021)	Goshen	Indiana
United States	Texas Oncology-Memorial City ( Site 8012)	Houston	Texas
United States	University of Texas-MD Anderson Cancer Center ( Site 0083)	Houston	Texas
United States	Baptist MD Anderson Cancer Center ( Site 0014)	Jacksonville	Florida
United States	Kadlec Clinic Hematology and Oncology ( Site 0070)	Kennewick	Washington
United States	Cedars Sinai Medical Center Samuel Oschin Comp. Cancer Institute ( Site 0079)	Los Angeles	California
United States	James Graham Brown Cancer Center ( Site 0022)	Louisville	Kentucky
United States	Bon Secours St. Francis Medical Center Oncology Research ( Site 0064)	Midlothian	Virginia
United States	El Camino Hospital Cancer Center ( Site 0004)	Mountain View	California
United States	Tennessee Oncology, PLLC/The Sarah Cannon Research Institute ( Site 7000)	Nashville	Tennessee
United States	Weill Cornell Medical College ( Site 0043)	New York	New York
United States	Southeastern Regional Medical Center, Inc. ( Site 0075)	Newnan	Georgia
United States	MGH Newton-Wellesley Hospital's Vernon Cancer Center ( Site 0082)	Newton	Massachusetts
United States	Virginia Oncology Associates ( Site 8001)	Norfolk	Virginia
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists ( Site 0039)	Omaha	Nebraska
United States	Stanford Cancer Center ( Site 0072)	Palo Alto	California
United States	Cancer Treatment Centers of America-Eastern Regional Medical Center ( Site 0076)	Philadelphia	Pennsylvania
United States	Fox Chase Cancer Center ( Site 0078)	Philadelphia	Pennsylvania
United States	Texas Oncology- Plano East ( Site 8010)	Plano	Texas
United States	OHSU Knight Cancer Institute ( Site 0051)	Portland	Oregon
United States	Mayo Clinic and Medical School (Rochester) ( Site 0029)	Rochester	Minnesota
United States	UC Davis Comprehensive Cancer Center ( Site 0073)	Sacramento	California
United States	Orchard Healthcare Research Inc. ( Site 0020)	Skokie	Illinois
United States	Medical Oncology Associates (Summit Cancer Centers) ( Site 0066)	Spokane	Washington
United States	Holy Name Medical Center ( Site 0041)	Teaneck	New Jersey
United States	Northwest Cancer Specialists, P.C. ( Site 8000)	Tigard	Oregon
United States	Arizona Oncology Associates PC- HOPE ( Site 8008)	Tucson	Arizona
United States	CTCA Southwestern ( Site 0074)	Tulsa	Oklahoma
United States	Texas Oncology-Tyler ( Site 8006)	Tyler	Texas
United States	MercyOne Waterloo Cancer Center ( Site 0016)	Waterloo	Iowa
United States	Midwestern Regional Medical Center, Inc. ( Site 0077)	Zion	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  China,  Colombia,  Costa Rica,  France,  Germany,  Hungary,  Ireland,  Israel,  Japan,  Korea, Republic of,  New Zealand,  Poland,  Portugal,  Puerto Rico,  Russian Federation,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

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

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary