ECLIPSE

• ECLIPSE is a novel, highly sensitive informatic method developed to track tumour evolution over time using low circulating tumour DNA (ctDNA) fraction samples (>0.1%) of liquid biopsies by leveraging genomic information for each mutation from a matched tumour tissue sample.
• ECLIPSE calculates the proportion of cancerous cells in a tumour that carries a specific mutation (the Cancer Cell Fraction for that mutation), providing unbiased information on the tumour and its evolution.
• ECLIPSE’s detection power for ctDNA is much higher than standard liquid biopsy methods and has been validated in silico and by in vitro spike-in experiments.
• ECLIPSE can identify subclonal genetic alterations that are likely to metastasise, enabling potential guidance of targeted therapy.
• ECLIPSE was developed by Alexander Frankell, Chris Abbosh, and Charlie Swanton at UCL and the Francis Crick Institute.
• A PCT application was filed in October 2022 with claims covering ECLIPSE methodology.

Understanding tumour heterogeneity is clinically important for patient prognosis, targeting therapy resistance, and predictions of immuno-oncology response. Multiregional, longitudinal tumour biopsies are not possible in standard clinical settings. Liquid biopsy and analysis of circulating tumour DNA can provide information on tumour heterogeneity and its evolution over time, however standard liquid biopsy methods require at least 10% circulating tumour DNA levels in the liquid biopsy samples. ECLIPSE can calculate the Cancer Cell Fraction for various genetic alterations in samples containing as little as 0.1% circulating tumour DNA. This high level of sensitivity means that ECLIPSE can detect subclones in plasma, which can be compared longitudinally to detect clonal evolution in tumours to enable the early identification of subclonal mutations that are likely to metastasize. This will eventually inform treatment of a patient over time.

The ECLIPSE methodology has been validated in a cohort of non-small cell lung cancer patients within the TRACERx (TRAcking Cancer Evolution through treatment (Rx)) Lung Study. In a cohort of ctDNA-positive samples within the TRACERx study, ECLIPSE detected clonal ctDNA in 61% of patients, while standard liquid biopsy methods detected clonal ctDNA in only 16% of patients. Furthermore, by assessing the clonal structure of cancers in patients over the course of their treatment, ECLIPSE enabled the detection of subclones that are resistant to therapy in the absence of a known resistance mechanism. Finally, measuring the size of subclones in metastatic patient samples using ECLIPSE allowed the likelihood of those subclones metastasising to be assessed, and in turn it may enable the guidance of targeted therapies to eradicate subclones before they metastasize.