Phase 3 Study of Pembro with/without Epacadostat in 1L Urothelial Carc
Research type
Research Study
Full title
A Phase 3 Randomized, Double-blind Trial of Pembrolizumab (MK-3475) in Combination with Epacadostat (INCB024360) or Placebo in Participants with Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307)
IRAS ID
235288
Contact name
Syed Hussain
Contact email
Sponsor organisation
Incyte Corporation
Eudract number
2017-002311-34
Clinicaltrials.gov Identifier
MK-3475-672(INCB024360-307), Full Sponsor's/protocol number
Duration of Study in the UK
years, 33 months, days
Research summary
Urothelial carcinoma (UC) is the most common type of bladder cancer in the United States and Western Europe, where it accounts for approximately 90% of bladder cancers. The worldwide incidence of bladder cancer exceeds 300,000 cases annually. There is relatively limited benefit from first-line chemotherapy in participants with advanced, inoperable or metastatic UC who cannot receive cisplatin. However, there are reports of promising results with immune checkpoint inhibitors, such as pembrolizumab and other anti-PD-1 (programmed cell death protein 1) pathway agents in this patient population.
Pembrolizumab (MK-3475) is a potent and highly selective monoclonal antibody (a type of protein made in the laboratory that can bind to substances in the body, including cancer cells) that targets and blocks PD-1 on the surface of certain immune cells called T-cells. Blocking PD-1 triggers the T-cells to find and kill cancer cells.
Epacadostat (INCB024360) is a novel, potent, and selective inhibitor of an enzyme called IDO1. This enzyme is found in both tumour cells and some of the immune system cells. The immune system is the body's defence against infectious organisms and other invaders that cause disease. Epacadostat acts by decreasing the tumour’s ability to stop anti-tumour immune response. Combined inhibition of both PD-L1 and IDO1 pathways may therefore lead to greater suppression of anti-tumour immunity and to increased effectiveness of treatment.
This is a randomised, active-controlled, parallel-group, multi- site, double-blind study of pembrolizumab in combination with epacadostat or placebo in approximately, 650 male/female participants aged ≥18yrs with UC who have not received prior systemic chemotherapy and who are not eligible to receive cisplatin. The study will last approximately 33 months.
The study is co- funded by Incyte Corporation and Merck Sharp & Dohme Limited and will take place at 7 study centres in the UK.
REC name
East of England - Cambridge South Research Ethics Committee
REC reference
17/EE/0480
Date of REC Opinion
31 Jan 2018
REC opinion
Further Information Favourable Opinion