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
This is a clinical study for adults with high-risk early stage ER+/HER2- breast cancer. The purposes of this study are to:
Pembrolizumab is being tested for high-risk early stage ER+/HER2-. Pembrolizumab is a humanized monoclonal antibody (a type of protein made in the laboratory that can bind to substances in the body, including cancer cells) that is given intravenously and acts as a checkpoint inhibitor (a molecule that blocks protein binding on immune cells) to allow immune system to participate in tumor cell destruction. It has not been approved to treat breast cancer, but it is approved to treat other types of cancer.
The chemotherapies being used in this study (Paclitaxel, Doxorubicin, Epirubicin and Cyclophosphamide) are approved, and widely used, as treatment for this type of breast cancer. Chemotherapy drugs kill or disable cancer cells.
Participants will also receive endocrine therapy as part of the treatment during the study. Endocrine therapy, tamoxifen and/or an aromatase inhibitor (anastrozole, letrozole or exemestane), is also approved to treat this type of breast cancer. Endocrine therapy drugs slow or stop the growth of hormone receptor-positive tumors by preventing the cancer cells from getting the hormones they need to grow.
The use of these drugs together with pembrolizumab is experimental.
Participants will placed into one of two groups, Group A or Group B, by chance, similar to flipping a coin, in order to decide which study treatment they will receive.
Pembrolizumab or placebo will be given by vein about once every 3 weeks. Participants have a 1 in 2 chance of getting placebo. Neither participants nor the study doctor will know what they are receiving. The chemotherapies listed above will all be given by vein.
Participants will have surgery within 6 weeks after Treatment Part 2. This surgery is standard of care, which means participants would have it even if they were not taking part in this study.
Depending on the initial stage of the disease and the treatment guidelines of the institution, participants may need radiation therapy.
The study doctor will choose which endocrine therapy participants will receive.
Participants will be in the study for about 12 years. When participants stop taking pembrolizumab or placebo, they will continue to visit the study doctor while on endocrine therapy up to 10 years.