Pembrolizumab & Chemoradiation in Oesophageal Carcinoma Participants

  • Research type

    Research Study

  • Full title

    A Randomized, Double-blind, Placebo-controlled Phase 3 Trial of Pembrolizumab (MK-3475) Versus Placebo in Participants with Esophageal Carcinoma Receiving Concurrent Definitive Chemoradiotherapy (KEYNOTE 975)

  • IRAS ID

    274432

  • Contact name

    Wasat Mansoor

  • Contact email

    was.mansoor@christie.nhs.uk

  • Sponsor organisation

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

  • Eudract number

    2019-002006-51

  • Clinicaltrials.gov Identifier

    NCT04210115

  • Duration of Study in the UK

    5 years, 10 months, 22 days

  • Research summary

    Oesophageal cancer is the eighth most commonly diagnosed cancer worldwide and the sixth most common cause of cancer-related death.

    Although surgery has been central to the curative treatment of oesophageal cancer for the past half of a century, half of patients are unsuitable for surgical resection at presentation for a variety of reasons. For locally advanced unresectable oesophageal cancer and medically inoperable oesophageal carcinoma, definitive (ie, with curative intent) chemoradiation (dCRT) has emerged as an important treatment strategy because it combines the effects of radiotherapy (RT) and chemotherapy to control the tumour locally.

    Programmed cell death 1 (PD1) is a protein present on the surface of immune (attacking) cells which fight cancer. When immune cells meet cancer cells, PD1 becomes activated by programmed cell death ligands 1 and 2 (PDL1 and PDL2) which are proteins on the surface of cancer cells. The activated immune cells die thus stopping them from attacking the cancer. The study drug pembrolizumab has been developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.

    The high unmet need, lack of effective approved therapies, and data from previous studies in patients with oesophageal carcinoma strongly support the clinical evaluation of pembrolizumab in combination with dCRT in this patient population.
    This multicentre phase 3 study will recruit approximately 600 male and female (18+) participants. The purpose of this study is to assess the effectiveness and safety of pembrolizumab plus dCRT, versus placebo plus dCRT in oesophageal carcinoma patients. Participants will be assigned randomly in 1:1 ratio to one of the two treatment arms.

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

  • REC name

    North West - Greater Manchester Central Research Ethics Committee

  • REC reference

    20/NW/0054

  • Date of REC Opinion

    31 Mar 2020

  • REC opinion

    Favourable Opinion