Pembrolizumab (MK-3475) plus Epacadostat vs SOC in mRCC
Research type
Research Study
Full title
A Randomized, Open-Label, Phase 3 Study to Evaluate Efficacy and Safety of Pembrolizumab (MK-3475) plus Epacadostat vs Standard of Care (Sunitinib or Pazopanib) as First-Line Treatment for Locally Advanced or Metastatic Renal Cell Carcinoma (mRCC) (KEYNOTE-679/ECHO-302)
IRAS ID
234205
Contact name
Thomas Powles
Contact email
Sponsor organisation
Incyte Corporation
Eudract number
2017-002259-26
Clinicaltrials.gov Identifier
Duration of Study in the UK
5 years, 3 months, 21 days
Research summary
Renal cell cancer (RCC) is the most common type of kidney cancer in adults. In RCC, cancerous cells start in the lining of the tubules (the smallest tubes inside the nephrons).
There is a continued unmet medical need for safe and effective combination therapies for clear-cell RCC because of toxicities with existing tyrosine-kinase inhibitors and inevitable relapse or disease progression with current treatments. Both indoleamine 2, 3-deoxygenase 1 (IDO1) and programmed cell death 1 (PD-1) receptors have been shown to suppress T-cell-mediated antitumor immunity, and IDO1 and the PD-1 ligand (PD-L1) have been shown to be co-expressed in multiple cancer types and to correlate with poor prognosis. Combined inhibition of both pathways may therefore lead to greater suppression of antitumour immunity and to increased effectiveness.
Pembrolizumab (MK-3475) is a potent and highly selective monoclonal antibody that directly blocks the interaction between PD-1 and its ligands, programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). The blockade increases functional activity of the target lymphocytes to facilitate tumour regression and ultimately immune rejection of the tumour.
Epacadostat (INCB024360) represents a novel, potent and selective inhibitor of the IDO1 enzyme in human tumour and dendritic cells. IDO1 is a key regulator of the immunosuppressive mechanisms responsible for tumour escape from immune surveillance.
This randomised, open-label, parallel group, Phase 3 study will evaluate the efficacy and
safety of pembrolizumab plus epacadostat compared to standard chemotherapy (sunitinib or pazopanib). Approximately 630 male/female participants aged ≥18 years with locally advanced/metastatic RCC (mRCC) with clear cell component will be enrolled. Participants must not have received prior systemic therapy for their mRCC. The trial will last approximately 5 years.The study is co-funded by Incyte Corporation and Merck Sharp & Dohme Limited and will take place at five study centres in the UK.
REC name
London - Fulham Research Ethics Committee
REC reference
17/LO/1939
Date of REC Opinion
28 Nov 2017
REC opinion
Favourable Opinion