Phase 2 Study of Pembrolizumab ± Epacadostat in Metastatic NSCLC
Research type
Research Study
Full title
A Phase 2, Randomized, Double-Blind Study of Pembrolizumab (MK-3475) plus Epacadostat (INCB024360) Versus Pembrolizumab plus Placebo as First-Line Treatment in Patients with Metastatic Non-Small Cell Lung Cancer Expressing High Levels of PD-L1
IRAS ID
233760
Contact name
Katy Clarke
Contact email
Sponsor organisation
Incyte Corporation
Eudract number
2017-001841-28
Duration of Study in the UK
5 years, 0 months, 13 days
Research summary
The most common type of lung cancer is non-small cell lung cancer (NSCLC) representing approximately 85% of all lung cancers. The global incidence of lung cancer was 1.8 million in 2012, resulting in an estimated 1.6 million deaths, according to the WHO. Approximately 70% of patients with NSCLC have advanced disease not amenable to surgical resection at the time of diagnosis.
Pembrolizumab (MK-3475) is a potent and highly selective monoclonal antibody that targets the programmed cell death protein 1 (PD-1) by directly blocking 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. Pembrolizumab monotherapy is the current standard of care (SOC) for the treatment of patients with good Eastern Cooperative Oncology Group assessments performance status and previously untreated, advanced, or metastatic NSCLC with a PD-L1 tumour proportion score (TPS) ≥50% with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumour aberrations.
Epacadostat (INCB024360) represents a novel, potent and selective inhibitor of the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) in human tumour cells and human dendritic cells. IDO1 is a key regulator of the immunosuppressive mechanisms responsible for tumour escape from immune surveillance. Combined inhibition of both PD-L1 and IDO1 pathways may therefore lead to greater suppression of antitumour immunity and increased effectiveness.
This is a randomised, double-blind, active-controlled, parallel-group, multi-site study of IV pembrolizumab and oral epacadostat in approximately 588 male/female participants aged ≥18yrs participants with stage IV NSCLC and PD-L1 TPS ≥50%. 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 3 study centres in the UK.
REC name
London - Central Research Ethics Committee
REC reference
17/LO/1806
Date of REC Opinion
3 Nov 2017
REC opinion
Favourable Opinion