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)
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)
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.
Inclusion Criteria:
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.
Exclusion Criteria:
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.
Goodyear, Arizona 85338, United States
Los Angeles, California 90048, United States
Newton, Massachusetts 02462, United States
Omaha, Nebraska 68130, United States
Philadelphia, Pennsylvania 19124, United States
Nashville, Tennessee 37203, United States
Dallas, Texas 75246, United States
Midlothian, Virginia 23114, United States
Spokane, Washington 99208, United States
Brussels, Bruxelles-Capitale, Region de 1200, Belgium
Goiânia, Goiás 74605-070, Brazil
Ijuí, Rio Grande do Sul 98700-000, Brazil
Porto Alegre, Rio Grande do Sul 90035-001, Brazil
Porto Alegre, Rio Grande do Sul 90610-000, Brazil
Itajaí, Santa Catarina 88301-220, Brazil
Rio de Janeiro, 20560121, Brazil
São Paulo, 01317-001, Brazil
Montreal, Quebec H1T 2M4, Canada
Québec, Quebec G1S 4L8, Canada
Heifei, Anhui 230001, China
Shanghai, Anhui 200025, China
Beijing, Beijing Municipality 100021, China
Fuzhou Fujian, Fujian 350001, China
Guangzhou, Guangdong 510289, China
Hangzhou, Jiangsu 310003, China
Tianjin, Tianjin Municipality 300060, China
Santa Ana, Provincia de San José 10903, Costa Rica
Essen, North Rhine-Westphalia 45136, Germany
Miskolc, Borsod-Abauj Zemplen county 3526, Hungary
Kecskemét, Bács-Kiskun county 6000, Hungary
Kitaadachi-gun, Saitama 362-0806, Japan
Suntogun, Shizuoka 411-8777, Japan
Wellington, 6021, New Zealand
Bydgoszcz, Kuyavian-Pomeranian Voivodeship 85-796, Poland
Ostrołęka, Masovian Voivodeship 07-410, Poland
Warsaw, Masovian Voivodeship 02-781, Poland
Bielsko-Biala, Silesian Voivodeship 43-300, Poland
Bytom, Silesian Voivodeship 41-900, Poland
Gliwice, Silesian Voivodeship 44-101, Poland
Lisboa, Aveiro District 1400-038, Portugal
Lisbon, 1649-035, Portugal
Porto, 4099-001, Portugal
Arkhangelsk, Arkhangelskaya oblast 163045, Russia
Ufa, Baskortostan, Respublika 450054, Russia
Saint Petersburg, Sankt-Peterburg 197758, Russia
Kazan', Tatarstan, Respublika 420029, Russia
L'Hospitalet de Llobregat, Barcelona 08908, Spain
Madrid, Madrid, Comunidad de 28007, Spain
Dnipro, Dnipropetrovsk Oblast 49102, Ukraine
Kryviy Rih, Dnipropetrovsk Oblast 50048, Ukraine
Ivano-Frankivsk, Ivano-Frankivsk Oblast 76018, Ukraine
Kharkiv, Kharkiv Oblast 61070, Ukraine
Antonivka Village, Kherson Oblast 73000, Ukraine
Khmelnitskiy, Khmelnytskyi Oblast 29000, Ukraine
Zaporizhzhya, Zaporizhzhia Oblast 69035, Ukraine
Bristol, Bristol, City of BS2 8ED, United Kingdom
London, London, City of SW17 0QT, United Kingdom