Use of a diagnostic assay to predict response to an anti-PD1 therapy
Research type
Research Study
Full title
Research protocol for the analytical validation and clinical use of a diagnostic assay to predict response to humanised monoclonal antibody directed against PD-1
IRAS ID
208840
Contact name
Richard Kennedy
Contact email
Sponsor organisation
Almac Diagnostics
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 7 months, 5 days
Research summary
The objective of this research study is to evaluate a diagnostic test that will predict response to a humanised monoclonal antibody directed against PD-1.
Programmed Cell Death-1 (PD-1) is expressed on the surface of activated T-cells (immune cells) and its normal function is to suppress immune responses. Healthy organs contain little of the ligand that PD-1 binds to (denoted PDL1) in order to maintain the appropriate level of immune response. However, a variety of cancers express abundant PDL1 to exacerbate suppression the immune system. Therefore, targeting the interaction between PD-1 and its ligand, PDL1, is an attractive strategy for therapeutic intervention.
Merck Sharpe and Dohme have developed pembrolizumab, a potent and highly selective humanized monoclonal antibody to block the interaction between PD-1 and PDL1, driving reactivation of immune surveillance and improving anti-tumour activity. The safety and efficacy of pembrolizumab has been evaluated in Phase I clinical trials involving advanced solid tumours. These studies have indicated that pembrolizumab is well tolerated in patients with advanced cancer.
Studies have shown that people respond differently to treatment with drugs such as pembrolizumab. A diagnostic assay which could predict the likelihood of response to this therapy prior to treatment would aid in the clinical management of patients with advanced solid tumours, preventing unnecessary exposure of non-responders to the side-effects of the therapy.
In the clinical trial setting, the diagnostic assay will be used to screen patients with advanced rare tumours to determine if they are likely to respond to anti-PD-1 therapy. If the assay predicts that the patient will respond to treatment, the patient will be enrolled onto a Phase II clinical trial and receive treatment with pembrolizumab. The data generated will be used to evaluate the performance of the assay i.e. determine if it can significantly and independently predict patient response to pembrolizumab.
REC name
HSC REC B
REC reference
16/NI/0114
Date of REC Opinion
14 Jun 2016
REC opinion
Favourable Opinion