Phase III pembro study in high-risk early-stage ER+/HER2–breast cancer

  • Research type

    Research Study

  • Full 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)

  • IRAS ID

    249396

  • Contact name

    Peter Schmid

  • Contact email

    p.schmid@qmul.ac.uk

  • Sponsor organisation

    Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

  • Eudract number

    2017-004869-27

  • Duration of Study in the UK

    12 years, 0 months, 11 days

  • Research summary

    Breast cancer is the most commonly diagnosed malignancy and the leading cause of cancer deaths in women worldwide. Oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2–) breast cancer is the most prevalent form of breast cancer, accounting for about 60% of all cases. ER+/HER2– breast cancer includes a subpopulation of patients that are at high risk of recurrence and have poor long-term outcome. This study has the potential to establish a novel treatment model, resulting in improved long-term outcomes, and possibly higher rates of cure, for a subpopulation of patients with aggressive early-stage ER+/HER2– breast cancer.

    Programmed cell death 1 (PD1) is a protein present on the surface of immune cells which fight cancer. When immune cells encounter cancer cells, PD1 becomes activated by programmed cell death ligands 1 and 2 (PDL1 and PDL2) found on the surface of cancer cells. Interaction between these ligands and their receptors prevents the immune cells from attacking the cancer cells. Pembrolizumab, the drug being tested in this study has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.

    This Phase III study will last approximately 12 years and will recruit 1140 men/women over the age of 18 with newly diagnosed high-risk ER+/HER2– breast cancer who are candidates for neoadjuvant (first step treatment) chemotherapy. Each participant will take part in the trial for approximately 12 years from the time they sign the Informed Consent Form through the final protocol-specified contact.

    The purpose of this study is to test safety and effectiveness of the study drug pembrolizumab compared to placebo, both in combination with neoadjuvant chemotherapy and adjuvant (additional) endocrine (hormone) therapy.

    The study is funded by Merck Sharp & Dohme Limited and will take place at 8 study centres in the UK.

  • REC name

    East of England - Cambridge East Research Ethics Committee

  • REC reference

    18/EE/0373

  • Date of REC Opinion

    27 Dec 2018

  • REC opinion

    Further Information Favourable Opinion