Phase 3 Study of Pembrolizumab with/without Epacadostat in UC
Research type
Research Study
Full title
Phase 3 Randomized, Double-Blind Clinical Study of Pembrolizumab + Epacadostat vs Pembrolizumab + Placebo as a Treatment for Recurrent or Progressive Metastatic Urothelial Carcinoma in Patients who have Failed a First-Line Platinum-containing Chemotherapy Regimen for Advanced/Metastatic Disease (KEYNOTE-698/ECHO-303)
IRAS ID
235808
Contact name
Thomas Powles
Contact email
Sponsor organisation
Incyte Corporation
Eudract number
2017-002310-31
Duration of Study in the UK
0 years, 36 months, 0 days
Research summary
Urothelial carcinoma (UC) is the predominant histologic type of bladder cancer in the United States and Western Europe. The worldwide incidence of bladder cancer exceeds 300,000 cases annually. UC accounts for approximately 90% of bladder cancers in the US/Western Europe.
Systemic chemotherapy is the standard approach for the initial treatment of patients with inoperable locally advanced/metastatic urothelial malignancies. Second-line chemotherapy, usually as a single agent, has had only a limited role and these regimens are toxic and provide limited benefit.
Programmed cell death 1 (PD1) is a receptor protein present on the surface of immune cells (T-cells), which fight cancer. When immune cells encounter cancer cells, PD1 becomes activated by programmed cell death ligands 1 and 2 (PDL1 and PDL2) proteins on the surface of cancer cells. Interaction between these ligands and the receptors prevents the immune cells from attacking the cancer cells. The study drug pembrolizumab has been designed to block PD1/PDL1 interaction to increase the immune attack on cancer cells.
Indoleamine 2,3 dioxygenase-1 (IDO1) is an enzyme found in cells. IDO1 inhibits T-cell mediated immune responses and it has been shown IDO1 expression is elevated in many cancers. Epacadostat is a novel, potent, selective inhibitor of IDO1 in cancer cells and may restore an effective antitumor immune response.
Combination of pembrolizumab and epacadostat has shown promising results for the treatment of advanced/metastatic disease, for those who have had progression or recurrence following a platinum containing chemotherapy regimen.
Approximately 648 participants (≥18yrs) will be randomized in a 1:1 ratio. The purpose of the study is to compare overall survival and progression-free survival in participants receiving pembrolizumab + epacadostat vs pembrolizumab + placebo.
The study is co-funded by MSD and Incyte and will take place at 7 study centres in the UK and will last approximately 36 months.
REC name
London - Fulham Research Ethics Committee
REC reference
17/LO/2059
Date of REC Opinion
29 Jan 2018
REC opinion
Further Information Favourable Opinion