Study conducted with investigators at Dana-Farber Cancer Institute showed ctDNA changes pre- and post-ICI therapy associated with resistance to treatment; Suggests liquid biopsy may be a useful tool for personalizing immunotherapy in patients with metastatic urothelial carcinoma
PALO ALTO – Precision oncology company Lucence, in collaboration with researchers at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, is sharing data highlighting the capabilities of its amplicon-based liquid biopsy technology to detect and characterize genomic alterations in ctDNA in patients with late-stage bladder cancer undergoing immunotherapy. The data will be presented as part of a virtual poster presentation at the European Society for Medical Oncology (ESMO) Congress 2021.
Urothelial carcinoma is the most common type of bladder cancer and immune checkpoint inhibitors (ICIs) are used as both first and second-line therapy for patients with metastatic urothelial carcinoma (mUC). Most mUC patients do not respond, or develop resistance to, ICI and obtaining tissue biopsies before and throughout treatment is invasive and presents risks of complications.
The poster, Serial ctDNA alterations using amplicon-based next-generation sequencing (NGS) to identify resistance mechanisms to immune checkpoint inhibitors (ICIs) for metastatic urothelial carcinoma (mUC)(Presentation Number 709P), identifies ctDNA alterations pre- and post-ICI therapy using Lucence’s 80 gene amplicon-based liquid biopsy panel, LiquidHALLMARK®, as a non-invasive method of exploring mechanisms of resistance to ICI.
The primary objective was to evaluate ctDNA alterations pre- and post-ICI therapy and to correlate these with response to ICI treatment. Out of 39 patients, the study found ctDNA alterations in 96% of pre/post-ICI samples overall, suggesting that longitudinal ctDNA profiling using a sensitive assay may be a useful clinical alternative to invasive biopsies. Clearance of TP53 alterations during ICI therapy was associated with response, while emergence of BRCA1/2 or PIK3CA variants appeared to be associated with resistance.
“Using this sensitive assay, we non-invasively evaluated genomic alterations in ctDNA in patients with advanced urothelial cancer before and after immune checkpoint inhibitor therapy,” said Guru Sonpavde, MD, the director of the bladder cancer program at Dana-Farber. “The emergence or disappearance of specific alterations during therapy was associated with resistance or response, respectively, suggesting this approach could be used to track disease status non-invasively, and provides insights into developing rational combinations of immunotherapy with targeted agents in a precision medicine approach.”
“Profiling ctDNA in bladder cancer patients with liquid biopsy pre- and post-ICI therapy presents a compelling opportunity to non-invasively characterize response and resistance to therapy based on the molecular characteristics of an individual’s disease,” said Dr. Min-Han Tan, MBBS, PhD, Founding CEO and Medical Director of Lucence. “Liquid biopsy allows us to identify actionable variants, such as FGFR fusions, with high sensitivity, without painful or risky biopsies, and can help us advance the development of personalized therapies in urothelial carcinoma.”
Lucence’s LiquidHALLMARK panel covers a wide range of clinically relevant biomarkers, including mutations in 80 genes, fusions in 10 genes, and somatic variants in 15 cancer types. LiquidHALLMARK is powered by AmpliMarkTM, the Company’s proprietary amplicon-based sequencing technology, which uses a unique molecular barcode and error-correction technology to ensure test sensitivity across multiple mutation types for single nucleotide variants and fusion genes.