PD-RAD
Research type
Research Study
Full title
A translational study investigating PD-L1 expression after radiotherapy for non-small cell lung cancer (NSCLC).
IRAS ID
180593
Contact name
Timothy Illidge
Contact email
Sponsor organisation
The Christie NHS Foundation Trust
Clinicaltrials.gov Identifier
Duration of Study in the UK
1 years, 4 months, 6 days
Research summary
Research Summary
Lung cancer is the leading cause of cancer mortality worldwide with approximately 40,000 new cases diagnosed annually in the UK. Currently, radiotherapy alone or combined with chemotherapy, plays a major therapeutic role in the treatment of non-small cell lung cancer (NSCLC). Despite this most patients still progress both locally and at sites of distant spread.
Recent phase I studies in NSCLC patients have demonstrated the immunogenicity of this tumour type – treatment with monoclonal antibodies (mAbs) targeting the PD-L1/PD-1 interaction between immune cells and tumour cells resulted in durable tumour regression and prolonged disease stabilisation in some patients. As such there is considerable interest in combining this class of agents with other anti-cancer therapies.
Further investigation within the NSCLC patient population is necessary to define how radiotherapy affects levels of PD-L1 expression in these tumours and to understand the impact on PD-L1 levels on responses to antibody therapy. It is unknown at present whether baseline PD-L1, or the change that occurs in PD-L1 expression levels after treatment will transpire to be of greater importance in predicting outcome of combined therapy.
The objective of the study is to demonstrate the feasibility of obtaining paired biopsies (biopsies taken before & after treatment) in NSCLC patients following radiotherapy treatment and determine if it is feasible to assess the change in PD-L1 expression levels following radiotherapy in these paired tumour samples.
Summary of Results
The main purpose of this study was to see if it would be feasible to conduct a larger study exploring the effect of radiotherapy on Programmed death-ligand 1 (PD-L1), an immune checkpoint ligand which has been shown to be upregulated by radiotherapy in murine models. This smaller, pilot study aimed to recruit 30 participants over 16 months from four centres and see if it was possible to 1) collect a pair of biopsies from each person, one before and one during treatment 2) measure PD-L1 from these samples and 3) see if this changes between the two samples for each person. Despite the best efforts of the team, only six participants were recruited into the study from two sites and a pair of biopsies were only able to be collected on half of these people. With so few samples, it was not possible to reliably look at change in PD-L1 over time. Such a low recruitment rate means that it would not be feasible to run a larger study. Overall, 6 patients were registered on study before the study closed early to recruitment due to COVID-19 restrictions (March 2020). Specifically, high quality tumour tissue and blood samples were collected from 5/6 registered patients. Tumour tissue pre- and during-radiotherapy were collected for 3/5 patients; Serial blood samples were collected for 4/5 patients. Tissue samples taken pre- and during-radiotherapy were assessed for Programmed death-ligand 1 (PD-L1) expression. The low number of patients recruited, and few samples collected meant that no meaningful statistical analysis could be performed on the dataset, meaning that the results had no impact on the treatment of non-small cell lung cancer. Tissue biopsies were also analysed by multiplex immunohistochemistry for various immune cells including T cells, macrophages and myeloid cells. Peripheral blood mononuclear cells were analysed by mass cytometry (Cytof) and the proportion of classical monocytes appeared to increase with radiotherapy. 34 cytokines and chemokines in the plasma were quantified by Luminex before, during and after radiotherapy. As the number of patients with samples available to analyse was so small (4 or 5 patients) no conclusions could be generated from the data. However these are hypothesis forming data which will guide future studies.
REC name
North West - Liverpool Central Research Ethics Committee
REC reference
17/NW/0552
Date of REC Opinion
8 Dec 2017
REC opinion
Further Information Favourable Opinion