Breast Cancer Clinical Trial
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)
The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) versus placebo in combination with neoadjuvant (pre-surgery) chemotherapy and adjuvant (post-surgery) endocrine therapy in the treatment of adults who have high-risk early-stage estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer.
The primary study hypotheses are: 1) pembrolizumab is superior to placebo, both in combination with the protocol-specified neoadjuvant anticancer therapy, as assessed by pathological Complete Response (pCR) rate defined by the local pathologist, and 2) pembrolizumab is superior to placebo (both in combination with the protocol-specified neoadjuvant and adjuvant anticancer therapies) as assessed by Event-Free Survival (EFS) as determined by the investigator. The study is considered to have met its primary objective if pembrolizumab is superior to placebo with respect to either pCR (ypT0/Tis ypN0) or EFS.
Study 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.
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.
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.
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There are 240 Locations for this study
Daphne Alabama, 36526, United States
Goodyear Arizona, 85338, United States
Tucson Arizona, 85704, United States
Los Angeles California, 90048, United States
Mountain View California, 94040, United States
Palo Alto California, 94304, United States
Sacramento California, 95817, United States
Aurora Colorado, 80045, United States
Jacksonville Florida, 32207, United States
Newnan Georgia, 30265, United States
Chicago Illinois, 60637, United States
Skokie Illinois, 60077, United States
Zion Illinois, 60099, United States
Goshen Indiana, 46526, United States
Waterloo Iowa, 50702, United States
Louisville Kentucky, 40202, United States
Bethesda Maryland, 20817, United States
Boston Massachusetts, 02114, United States
Danvers Massachusetts, 01923, United States
Newton Massachusetts, 02462, United States
Detroit Michigan, 48202, United States
Rochester Minnesota, 55905, United States
Billings Montana, 59102, United States
Omaha Nebraska, 68130, United States
Teaneck New Jersey, 07666, United States
New York New York, 10065, United States
Tulsa Oklahoma, 74133, United States
Portland Oregon, 97239, United States
Tigard Oregon, 97223, United States
Danville Pennsylvania, 17822, United States
Philadelphia Pennsylvania, 19111, United States
Philadelphia Pennsylvania, 19124, United States
Charleston South Carolina, 29425, United States
Nashville Tennessee, 37203, United States
Austin Texas, 78731, United States
Dallas Texas, 75231, United States
Dallas Texas, 75246, United States
Houston Texas, 77024, United States
Houston Texas, 77030, United States
Plano Texas, 75075, United States
Tyler Texas, 75702, United States
Midlothian Virginia, 23114, United States
Norfolk Virginia, 23502, United States
Kennewick Washington, 99336, United States
Spokane Washington, 99208, United States
Camperdown New South Wales, 2050, Australia
Sydney New South Wales, 2065, Australia
Sydney New South Wales, 2145, Australia
South Brisbane Queensland, 4101, Australia
Frankston Victoria, 3199, Australia
Melbourne Victoria, 3000, Australia
Bonheiden Antwerpen, 2820, Belgium
Edegem Antwerpen, 2650, Belgium
Anderlecht Bruxelles-Capitale, Region De, 1070, Belgium
Brussels Bruxelles-Capitale, Region De, 1200, Belgium
Liège Liege, 4000, Belgium
Hasselt Limburg, 3500, Belgium
Yvoir Namur, 5530, Belgium
Gent Oost-Vlaanderen, 9000, Belgium
Leuven Vlaams-Brabant, 3000, Belgium
Kortrijk West-Vlaanderen, 8500, Belgium
Goiania Goias, 74605, Brazil
Ijui Rio Grande Do Sul, 98700, Brazil
Porto Alegre Rio Grande Do Sul, 90035, Brazil
Porto Alegre Rio Grande Do Sul, 90610, Brazil
Florianopolis Santa Catarina, 88034, Brazil
Itajai Santa Catarina, 88301, Brazil
São Paulo Sao Paulo, 04014, Brazil
Rio de Janeiro , 20560, Brazil
Sao Paulo , 01246, Brazil
Sao Paulo , 01317, Brazil
Edmonton Alberta, T6G 1, Canada
Vancouver British Columbia, V5Z 4, Canada
Toronto Ontario, M5G 2, Canada
Greenfield Park Quebec, J4V 2, Canada
Montreal Quebec, H1T 2, Canada
Montreal Quebec, H2X 3, Canada
Montreal Quebec, H3T 1, Canada
Trois-Rivières Quebec, G8Z 3, Canada
Quebec , G1S 4, Canada
Heifei Anhui, 23000, China
Shanghai Anhui, 20002, China
Beijing Beijing, 10002, China
Fuzhou Fujian Fujian, 35000, China
Guangzhou Guangdong, 51028, China
Shijia Zhuang Hebei, 05001, China
Harbin Heilongjiang, 15008, China
Zhengzhou Henan, 45000, China
Wuhan Hubei, 43007, China
Changsha Hunan, 41000, China
Hangzhou Jiangsu, 31000, China
Changchun Jilin, 13002, China
Shanghai Shanghai, 20003, China
XI An Shanxi, 71006, China
Tianjin Tianjin, 30006, China
Urumqi Xinjiang, 83000, China
Hangzhou Zhejiang, 31001, China
Hangzhou Zhejiang, 31002, China
Medellin Antioquia, 05003, Colombia
Medellin Antioquia, 05003, Colombia
Barranquilla Atlantico, 08002, Colombia
Monteria Cordoba, 23000, Colombia
Bogota Distrito Capital De Bogota, 11022, Colombia
Bogota Distrito Capital De Bogota, 11122, Colombia
Cali Valle Del Cauca, 76004, Colombia
Santa Ana San Jose, 10903, Costa Rica
Caen Calvados, 14000, France
Dijon Cote-d Or, 21079, France
Toulouse Haute-Garonne, 31059, France
Saint-Cloud Hauts-de-Seine, 92210, France
Montpellier Herault, 34070, France
Metz Moselle, 57085, France
Lille Nord-Pas-de-Calais, 59000, France
Avignon Provence-Alpes-Cote-d Azur, 84918, France
Clermont Ferrand Cedex Puy-de-Dome, 63011, France
Le Mans Sarthe, 72000, France
Villejuif Val-de-Marne, 94805, France
Paris , 75005, France
Paris , 75010, France
Paris , 75020, France
Friedrichshafen Baden-Wurttemberg, 88045, Germany
Erlangen Bayern, 91054, Germany
Muenchen Bayern, 80337, Germany
Offenbach Hessen, 63069, Germany
Wiesbaden Hessen, 65199, Germany
Hannover Niedersachsen, 30177, Germany
Bonn Nordrhein-Westfalen, 53111, Germany
Essen Nordrhein-Westfalen, 45136, Germany
Paderborn Nordrhein-Westfalen, 60314, Germany
Saarbruecken Saarland, 66113, Germany
Dresden Sachsen, 01307, Germany
Nordhausen Thuringen, 99734, Germany
Kecskemet Bacs-Kiskun, 6000, Hungary
Pecs Baranya, 7621, Hungary
Miskolc Borsod-Abauj-Zemplen, 3526, Hungary
Budapest , 1032, Hungary
Budapest , 1122, Hungary
Budapest , 1145, Hungary
Debrecen , 4032, Hungary
Kaposvar , 7400, Hungary
Cork , T12 D, Ireland
Dublin , 8, Ireland
Afula , 18341, Israel
Ashdod , 77476, Israel
Beer Sheva , 84101, Israel
Haifa , 31096, Israel
Jerusalem , 91031, Israel
Jerusalem , 91120, Israel
Kfar-Saba , 44281, Israel
Nazareth , 16411, Israel
Petah Tikva , 49414, Israel
Ramat Gan , 52620, Israel
Rehovot , 76610, Israel
Tel Aviv , 64239, Israel
Tel Aviv , 67891, Israel
Nagoya Aichi, 464-8, Japan
Kashiwa Chiba, 27785, Japan
Sapporo Hokkaido, 003-0, Japan
Nishinomiya Hyogo, 663-8, Japan
Sagamihara Kanagawa, 252-0, Japan
Hidaka Saitama, 350-1, Japan
Kitaadachi-gun Saitama, 362-0, Japan
Sunto-gun Shizuoka, 411-8, Japan
Chiba , 260-8, Japan
Fukushima , 960-1, Japan
Hiroshima , 730-8, Japan
Kumamoto , 860-8, Japan
Osaka , 540-0, Japan
Tokyo , 105-8, Japan
Tokyo , 135-8, Japan
Tokyo , 142-8, Japan
Goyang-si Kyonggi-do, 10408, Korea, Republic of
Songpagu Seoul, 05505, Korea, Republic of
Seoul , 03080, Korea, Republic of
Seoul , 03722, Korea, Republic of
Seoul , 06351, Korea, Republic of
Tauranga Bay Of Plenty, 3112, New Zealand
Christchurch Canterbury, 8011, New Zealand
Wellington , 6021, New Zealand
Wrocław Dolnoslaskie, 53-41, Poland
Bydgoszcz Kujawsko-pomorskie, 85-79, Poland
Lodz Lodzkie, 93-33, Poland
Ostroleka Mazowieckie, 07-41, Poland
Warszawa Mazowieckie, 02-78, Poland
Wieliszew Mazowieckie, 05-13, Poland
Bialystok Podlaskie, 15-02, Poland
Gdansk Pomorskie, 80-21, Poland
Gdynia Pomorskie, 81-51, Poland
Bielsko-Biala Slaskie, 43-30, Poland
Bytom Slaskie, 41-90, Poland
Gliwice Slaskie, 44-10, Poland
Lisboa Aveiro, 1649-, Portugal
Lisboa , 1649-, Portugal
Porto , 4099-, Portugal
Porto , 4200-, Portugal
San Juan , 00935, Puerto Rico
Arkhangelsk Arkhangel Skaya Oblast, 16304, Russian Federation
Ufa Baskortostan, Respublika, 45005, Russian Federation
Moscow Moskva, 11547, Russian Federation
Moscow Moskva, 12135, Russian Federation
Moscow Moskva, 12536, Russian Federation
Ryazan Ryazanskaya Oblast, 39001, Russian Federation
Saint Petersburg Sankt-Peterburg, 19527, Russian Federation
Saint Petersburg Sankt-Peterburg, 19775, Russian Federation
Kazan Tatarstan, Respublika, 42002, Russian Federation
Tomsk Tomskaya Oblast, 63402, Russian Federation
Hospitalet de Llobregat Barcelona, 08908, Spain
A Coruna La Coruna, 15006, Spain
Madrid Madrid, Comunidad De, 28007, Spain
Pozuelo de Alarcon Madrid, 28223, Spain
Valencia Valenciana, Comunitat, 46011, Spain
Barcelona , 08023, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Jaen , 23007, Spain
Madrid , 28034, Spain
Madrid , 28040, Spain
Madrid , 28041, Spain
Sevilla , 41013, Spain
Valencia , 46015, Spain
Taichung , 40447, Taiwan
Tainan , 704, Taiwan
Taipei , 10048, Taiwan
Taipei , 11259, Taiwan
Taoyuan , 333, Taiwan
Dnipro Dnipropetrovska Oblast, 49102, Ukraine
Kryviy Rih Dnipropetrovska Oblast, 50048, Ukraine
Ivano-Frankivsk Ivano-Frankivska Oblast, 76018, Ukraine
Kharkiv Kharkivska Oblast, 61070, Ukraine
Antonivka Village Khersonska Oblast, 73000, Ukraine
Khmelnitskiy Khmelnytska Oblast, 29000, Ukraine
Kyiv Kyivska Oblast, 03022, Ukraine
Odesa Odeska Oblast, 65025, Ukraine
Odesa Odeska Oblast, 65055, Ukraine
Zaporizhzhia Zaporizka Oblast, 69035, Ukraine
Kyiv , 03115, Ukraine
Bristol Bristol, City Of, BS2 8, United Kingdom
Nottingham England, ng5 1, United Kingdom
Colchester Essex, CO4 5, United Kingdom
London London, City Of, EC1A , United Kingdom
London London, City Of, SE1 9, United Kingdom
London London, City Of, SW17 , United Kingdom
Solihull , B91 2, United Kingdom
Truro , TR1 3, United Kingdom
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