Positive study results said to support deployment of assay system in cancer drug clinical trials

By Jane Byrne

- Last updated on GMT

© GettyImages/anyaivanova
© GettyImages/anyaivanova

Related tags Assay

New research findings suggest that an immunotherapy assay enables determination of PD-L1 status in a high percentage of cancer patients and could guide personalized treatment selection.

Liquid biopsy company, ANGLE, is presenting the results of two studies evaluating the effectiveness of two assays at the virtual American Association for Cancer Research Conference (AACR) 2021, being held virtually from April 10-15.

One poster, Mesenchymal markers: the new avenue for circulating tumor cells detection​, reports on the performance of its new epithelial-to-mesenchymal transition (EMT) assay to isolate and identify both epithelial and mesenchymal circulating tumor cells (CTCs) in 47 metastatic breast cancer (MBC) and 48 non-small cell lung cancer (NSCLC) patients.

Unlike tissue biopsy, a liquid biopsy harvesting CTCs from peripheral blood allows the routine, repeat testing and characterization of cancer at genetic (DNA), transcriptional (RNA) and protein levels, claims the assay developer.

“Most CTC isolation systems, including the market leader, are based on epitope-dependent CTC capture using epithelial markers. However, it is known that tumor cells can undergo EMT resulting in these clinically relevant cells being missed by epitope-dependent systems.”

The company said its Parsortix system addresses this major limitation by its epitope-independent proprietary approach to capture all phenotypes of cancer cell in the blood circulation.

“This study highlighted the importance of the inclusion of mesenchymal markers into CTC characterization, as 25-38% of CTCs captured by the Parsortix system expressed mesenchymal markers which would have been missed with an epithelial-only based approach. In addition, 59%-74% of CTCs had both epithelial and mesenchymal markers and were therefore undergoing EMT whilst only 1-3% of CTCs were purely epithelial.”

It added that its EMT assay showed a high degree of analytical sensitivity (97-98%) and specificity (96-98%) in spiking experiments and these findings were confirmed in patient samples (96% specificity).

Tracking PD-L1 expression

Another poster, Investigation of PD-L1 expression in circulating tumor cells isolated using the Parsortix system in metastatic lung and breast cancer patients, ​documents results for the company’s programmed death-ligand 1 (PD-L1) assay.

PD-L1 is a protein thought to play a major role in immune-oncology, allowing many cancers to evade the host immune system when upregulated. Immunotherapy drugs known as PD-L1 inhibitors are showing excellent therapeutic results in multiple cancers for some patients. However, these drugs are expensive, at around US$170K per treatment and only work in about 30% of patients. ANGLE said this challenge shows the need for companion diagnostics to enable targeted patient selection.

The measurement of PD-L1 expression from CTCs offers the potential to identify patients who might respond to such immunotherapy drugs and, importantly, to monitor patients on these therapies using a drug-specific target, said ANGLE.

The results of its study in 17 MBC and 18 metastatic NSCLC patients found CTCs in 70% and 55% of patients respectively.

The company said no CTCs were found in 17 healthy volunteers, confirming high specificity. The PD-L1 assay allowed for definitive identification of PD-L1 positive and PD-L1 negative status in a high proportion of patients with CTCs (72% of MBC and 60% of NSCLC) with the remaining patients having a mix of PD-L1 positive and PD-L1 negative CTCs, it confirmed. 

The research work lays the groundwork for the further refinement of the assay to enable dynamic PD-L1 monitoring in patients during the course of their treatment and follow-up, said the assay producer.

“Future drug trials of immune checkpoint inhibitors will be targets for adoption of the Parsortix PD-L1 assay and ANGLE is developing a pharma services capability to process these types of trial samples for multiple such biomarkers on a commercial scale,” ​company founder and CEO, Andrew Newland, commented.

ANGLE recently launched clinical services laboratories in the UK and the US and outline how it is in advanced discussions with potential customers for the deployment of the Parsortix system in cancer drug clinical trials, highlighting how there are over 2,000 PD-L1/PD-1 interventional trials registered on clinicaltrials.gov, enrolling over 300,000 patients, which would be potential targets for its pharma services business. “We look forward to updating the market on the first contracts in due course.” 

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