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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 ER+/HER2– Breast Cancer

Clinical Trial Details

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:

  • Test the safety of the study drug, pembrolizumab (MK-3475) with certain types of chemotherapy and endocrine therapy
  • See how well the study drug, pembrolizumab, works when combined with chemotherapy and endocrine therapy, compared to these treatments alone, in the treatment of high-risk early stage ER+/HER2- breast cancer
  • See if combining the study drug with chemotherapy will have a positive outcome on the participants' surgery, compared to these treatments alone
  • See if combining the study drug with chemotherapy and endocrine therapy prevents participants' cancer from returning sooner (if at all), compared to these treatments alone
  • See if combining the study drug with chemotherapy and endocrine therapy helps participants live longer, compared to these treatments alone
  • See how participants' body handles the study drug

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.

Group A

  • Treatment Part 1: pembrolizumab plus paclitaxel for 4 cycles
  • Treatment Part 2: pembrolizumab plus doxorubicin (or epirubicin) plus cyclophosphamide for 4 cycles
  • Treatment Part 3: pembrolizumab for 9 cycles plus endocrine therapy for up to 10 years

Group B

  • Treatment Part 1: placebo (this is a look-alike with no active ingredients) plus paclitaxel for 4 cycles
  • Treatment Part 2: placebo plus doxorubicin (or epirubicin) plus cyclophosphamide for 4 cycles
  • Treatment Part 3: placebo for 9 cycles plus endocrine therapy for up to 10 years

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.

Surgery
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.

Radiation Therapy
Depending on the initial stage of the disease and the treatment guidelines of the institution, participants may need radiation therapy.

Endocrine 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.

Key Eligibility: 
  • Adults with with newly diagnosed, previously untreated, high-risk early-stage ER+/HER2– breast cancer
  • Candidates for neoadjuvant chemotherapy
  • Detailed eligibility will be reviewed when you contact the study team

Study contact by location

Upper East Side - Manhattan

Contact(s)

Marta Vallee Cobham, RN, BSN
(212) 821-0780
mac2034@med.cornell.edu

Primary Investigator(s)

Protocol ID(s)

Weill Cornell Medicine IRB #:

1904020063

ClinicalTrials.gov:

NCT03725059

Sponsor:

KEYNOTE-756

Status

Open to Enrollment

Age Group

Adult

Sponsor