Immunotherapy based on immune checkpoint inhibitors (ICIs) has revolutionised cancer treatment. Currently, ICIs are widely used as standard-of-care for lung cancer, melanoma, head and neck cancer, kidney cancer and others, achieving unprecedented durable remissions. However, response varies widely between patients, with the majority experiencing resistance to therapy. Moreover, ICIs carry the risk of severe toxicities. The increasing use of these costly drugs coupled with their unpredictable response and toxicity profiles underscore the need for biomarkers to identify patients who are likely to benefit from ICIs. Such biomarkers would facilitate precise, safe and cost-effective treatments.
To date, approved biomarkers for determining eligibility for ICIs are not optimal; they have modest predictive performance and testing generally requires a tumour biopsy sampled by an invasive procedure that is not always possible. Thus, there is still an unmet need for robust predictive ICI biomarkers, preferably those that are easily accessible (e.g. from a blood sample).
The NeutroFlow project directly addresses this need by developing a clinical test for predicting therapeutic benefit from ICIs based on flow cytometry analysis of patient blood samples. The flow cytometry-based test is designed to measure a specific neutrophil subtype in the blood, named Ly6E-high neutrophil, with proven potential to serve as a powerful, pan-cancer biomarker for ICIs. Such a test could potentially support treatment decisions, advancing personalised medicine for cancer patients.
The EIC Transition project aims to bridge the gap between research-level results and an industry-level prototype test. Specific objectives are to:
(i) Develop a prototype NeutroFlow kit and flow cytometry assay according to clinical standards for the detection of Ly6Ehi neutrophils in blood samples.
(ii) Establish a clinical study for the collection of pretreatment blood samples and clinical data from at least 600 cancer patients across six solid cancer types: non-small cell lung cancer; melanoma; head and neck squamous carcinoma; triple negative breast cancer; renal cell carcinoma; urothelial cancer. The samples and data will be used for the development and validation of the NeutroFlow test.
(iii) Acquire flow cytometry data from >600 patient samples using the prototype NeutroFlow kit and assay.
(iv) Develop and clinically validate a predictive model that translates the flow cytometry assay readout into a prediction of clinical benefit.
(v) Perform an analytical validation study to assess standardisation of the test across laboratories.
(vi) Map the regulatory pathway required for future approval of the product.
(vii) Manage and expand the IP portfolio to protect all aspects of the product.
(viii) Prepare for future commercialisation including market research, business model development, and consulting with a KOL committee about clinical utility of the test.
