An innovative telomerase-targeted, circulating tumor cell assay for monitoring NSCLC treated with radiation and immunotherapy

Project Summary: Cancer is a leading cause of death both in the United States and across the world, claiming over 600,000 and 8 million deaths each year, respectively. Delayed detection of cancer progression or recurrence after treatment contributes to increased morbidity and rapid death, but re-biopsy or repeat surgery is usually not possible due to

severe risks. The accuracy of conventional imaging modalities for timely detection is limited, especially after radiation- and immunotherapy, when treatment-induced edema/ inflammation mimics cancer progression. Thus,

there is an urgent need for safe, reliable, and non-invasive serial biomarkers (“liquid biopsies”) that provide “real- time” information of the status of a wide range of solid cancers. Liquid Biotech has collaborated with academia and NRG cancer cooperative group to develop the TelomeScan circulating tumor cell (CTC) assay for fulfilling

these unmet needs. TelomeScan has unique advantages including the detection of elevated telomerase activity (which contributes to immortality and is a hallmark of cancer) in live cancer cells (the component of tumors that most directly lead to tumor progression and metastasis), and imperviousness to the epithelial-mesenchymal

transition (EMT) that frequently occurs in cancer. TelomeScan has consistently shown it can detect cancer recurrence in patients with non-small cell lung cancer (NSCLC) six months to 2-years before conventional diagnostic imaging, thus providing valuable lead-time for actionable therapeutic intervention while minimizing

unintended side effects and cost of treatment that is no longer effective. Liquid Biotech has continued upon these efforts by providing availability of the assay in a centralized laboratory for multi-center clinical studies. We are currently near completion on two additional clinical trials, including for NSCLC in collaboration with NRG

Oncology. The goal of this project is to develop TelomeScan into a commercially available product that can benefit a broader range of patients. Aim 1 will develop a clinical prototype for the TelomeScan test incorporating automated analysis to handle substantially higher volumes of samples, thus expanding access and cancer

coverage. Aim 2 will develop the quantification of PD-L1 staining in TelomeScan identified NSCLC cells and CTCs, by monitoring pre- and post-treatment samples from patients undergoing or eligible for radiation and immunotherapy. These aims will lead to expanded access to benefit a far greater number of patients with NSCLC

and other cancers (Phase II).