Pembrolizumab/placebo in combination with CRT- locally advanced HNSCC
Research type
Research Study
Full title
A Randomized Phase III study of pembrolizumab given concomitantly with chemoradiation and as maintenance therapy versus chemoradiation alone in subjects with locally advanced head and neck squamous cell carcinoma (KEYNOTE-412)
IRAS ID
219974
Contact name
Kevin Harrington
Contact email
Sponsor organisation
Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc.
Eudract number
2016-003934-25
Duration of Study in the UK
3 years, 11 months, 21 days
Research summary
Research Summary
Head and neck cancer describes a range of tumours in the head and neck area, which includes the cavity of mouth and nose, pharynx, larynx, sinuses, thyroid, and salivary glands. Over 600,000 cases of head and neck cancer occur annually worldwide. Although the head and neck region contains many structures and types of cells, most head and neck cancers start from the lining of the upper respiratory and digestive tract and mainly begin in cells called squamous cells. Around 50% of head and neck squamous cell carcinomas (HNSCC) are diagnosed at a locally advanced stage (where the cancer has spread adjacently). The 5-year survival rate for HNSCC remains low.
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 become exhausted or 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.
This phase III study will last approximately 6 years (1 year treatment; 5 years follow-up) and will recruit approximately 780 men and women over the age of 18 with locally advanced HNSCC.
The purpose of the study is to evaluate the safety and effectiveness of pembrolizumab given with chemoradiation (a combination of chemotherapy and radiotherapy) and as a maintenance therapy versus placebo with chemoradiation. Participants will be assigned randomly in a 1:1 ratio to one of the two arms of trial. Participants may receive treatment for up to 1 year.
The study is funded by Merck Sharp & Dohme Limited and will take place at 8 study centres in UK.
Lay summary of results
Please see lay summary on: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT03040999%2FNBTI%2FQDO-AQ%2FAQ%2Fac920651-47ea-4232-b293-1f8619279e50%2F1%2FsYr4FQRVUh&data=05%7C02%7Cdulwich.rec%40hra.nhs.uk%7Cb3cb4daf1e5b484abcb608ddd5b98727%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638901715019747146%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=73mM7erlyoB%2BiqKkQm3bPvvUi9lgAqJGlQBcX8Y1ms8%3D&reserved=0
REC name
London - Dulwich Research Ethics Committee
REC reference
17/LO/0339
Date of REC Opinion
18 Apr 2017
REC opinion
Further Information Favourable Opinion