MK-3475-224: MK-3475 in subjects with previously treated HCC
Research type
Research Study
Full title
A Phase 2 Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects with Advanced Hepatocellular Carcinoma (KEYNOTE-224)
IRAS ID
200094
Contact name
Debashis Sarker
Contact email
Sponsor organisation
Merck Sharp and Dohme Ltd
Eudract number
2015-004566-28
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
KEYNOTE, 224
Duration of Study in the UK
1 years, 4 months, 8 days
Research summary
Summary of Research
Liver cancer is the second world-leading cause of cancer deaths. Most Hepatocellular Carcinoma (HCC) arises in the setting of liver cirrhosis from varied causes, including viral hepatitis or excessive alcohol consumption. As a consequence of these different causes, HCC is a heterogeneous malignancy (tumour that can spread and eventually cause serious or fatal damage).
Despite advances in early detection, liver transplantation and liver-directed therapies, about 70% of HCC patients present with advanced disease with no curative option. HCC is resistant to most traditional chemotherapy agents, and the median survival for patients with advanced disease is typically 6–9 months without therapy. There are no agents or combinations yet approved for previously treated HCC (or second line HCC), underscoring the high unmet medical need for this disease.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) 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 is a potent and highly selective humanised monoclonal antibody developed to block PD1/PDL1 interaction, thereby increasing the immune attack on cancers.
Approximately 100 male/female patients older than 18 with previously systemically treated HCC may be enrolled in this phase II study which will last approximately 24 months. The purpose of this study is to evaluate the efficacy of pembrolizumab given as monotherapy.
Subjects will receive 200mg intravenously (IV) of pembrolizumab on Day 1 of each 3-week dosing cycle for up to two years.
The study is funded by Merck Sharp & Dohme Limited and will take place at 2-3 study centres in the UK.
Summary of Results
https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT02702414%253Fterm%253D3475-224%2526rank%253D1%2526tab%253Dresults%2FNBTI%2FHPi3AQ%2FAQ%2F18747c83-18fb-4c95-a851-11050cee0eb7%2F2%2FgMkcU90OZ6&data=05%7C02%7Clondoncentral.rec%40hra.nhs.uk%7C72dbfb19e7634a15a40408dcd31f8c40%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638617379651033742%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=qdVJvmS63xss5%2F307XSzkx5VJERgX4oZlY%2BA5cnSx1M%3D&reserved=0
REC name
London - Central Research Ethics Committee
REC reference
16/LO/0805
Date of REC Opinion
6 May 2016
REC opinion
Favourable Opinion