Development and validation of a pan-cancer neutrophil biomarker test for predicting clinical benefit from immunotherapy based on flow cytometry analysis of blood samples

Introduction

The recent introduction of cancer immunotherapy based on immune checkpoint inhibitors (ICIs) has revolutionised the treatment landscape for a broad range of cancer types. However, response to ICIs varies widely between patients, with the majority experiencing resistance to therapy.

Economic Burden

Moreover, the increasing use of these costly drugs coupled with the management of ICI-related toxicities creates a substantial economic burden. Current biomarker tests for determining eligibility for ICIs have limited predictive performance, and many require invasive tumour biopsies.

Need for Novel Biomarkers

Thus, novel (and preferentially non-invasive) biomarkers for predicting ICI clinical benefit are desperately needed for better guiding clinical decisions. The NeutroFlow project directly addresses this unmet need.

Project Overview

We build on comprehensive academic research describing a flow cytometry assay for measuring a novel predictive biomarker in the blood – Ly6Ehi neutrophil – that accurately predicts therapeutic benefit from ICIs, outperforming the approved PD-L1 biomarker.

Objectives

The NeutroFlow project aims to upgrade the research-level assay to an industry-level, point-of-care prototype test based on a kit comprised of an antibody panel for biomarker detection by standard flow cytometry (FC). Specifically, we will:

1. Develop an FC assay according to clinical standards.
2. Develop and clinically validate a computational model that translates FC readout into a prediction of clinical benefit.
3. Evaluate analytical validity of the prototype across three medical centres (i.e., at the point-of-care).
4. Prepare for future market introduction.

Future Product

The future product represents a minimally-invasive, simple, rapid, cost-effective test performed using standard hospital equipment. As a pan-cancer blood test for accurately predicting ICI therapeutic benefit, the product will potentially expand the benefit of ICIs to more patients, improve quality of life, limit the risk of ICI-related toxicities, and reduce economic burden.