March 27, 2018 Source: Carislifesciences 181
Caris Life Sciences®, a leading innovator in molecular science focused on fulfilling the promise of precision medicine, today announced publication of an article that demonstrated the Company’s proprietary ADAPT Biotargeting System™ (ADAPT) significantly out-performed standard HER2 testing in predicting response to trastuzumab (Herceptin®) for breast cancer patients. The study, entitled “Polyligand Profiling Differentiates Trastuzumab-Treated Breast Cancer Patients According to Their Outcomes,” was published in Nature Communications [DOI: 10.1038/s41467-018-03631-z].
“Although current companion diagnostics have made a positive impact in cancer care, much more can be done. For example, the response rate for vemurafenib in melanoma with a V600E mutation is only about 50 percent. Similarly, the response rate for olaparib for BRCA-positive ovarian cancer is less than 35 percent,” said David D. Halbert, Chairman and CEO of Caris Life Sciences. “We know we can do better and this study proves that our proprietary technology can be utilized to develop dramatically superior companion diagnostic tests for existing and emerging therapeutics. The ADAPT Biotargeting System is providing unrivaled molecular insights and is primed to up-end conventional profiling as the new standard of molecular profiling for the future.”
“Only 38-50 percent of HER2-positive breast cancer patients derive benefit from trastuzumab, which underscores the need for diagnostic assays with improved performance for this patient population,” David Spetzler, M.S., Ph.D., M.B.A., President and Chief Scientific Officer of Caris Life Sciences, and senior author of the paper. “This proof-of-concept study conducted by leading researchers, clinicians and biostatisticians confirms that the ADAPT Biotargeting System is able to detect subtle variations in molecular networks that underlie response to trastuzumab, significantly out-performing traditional HER2 testing.”
Pre-treatment tumor samples were collected and divided into two groups based on their treatment responses: patients who benefited (B, time to next therapy (TTNT) greater than 12 months) and patients who did not benefit (NB, TTNT less than 3 months). An ADAPT library of 1013 unique single-stranded DNA (ssDNA) probes was subjected to several rounds of positive and negative selection to identify sub-libraries that preferentially bound to tumor sections from either B or NB patients. This enrichment phase resulted in two mature libraries, one each that preferentially bound to samples from either B or NB patients.
The investigators next evaluated the performance of the enriched libraries on an independent cohort of 61 patient samples, including 39 HER2 positive and 22 HER2 negative/equivocal patients. As shown in the accompanying figure, by comparing areas under the curves in receiver-operating characteristic plots (ROC-AUC), poly-ligand profiling (PLP) by ADAPT significantly outperformed conventional HER2 testing (ROC-AUC of 0.81 versus 0.47, respectively). Kaplan-Meier plots showed a median increase in benefit from trastuzumab-containing treatments of 300 days in PLP-positive versus PLP-negative patients.
“This study is among the most exciting and useful applications of aptamer technology to date,” said Professor Michael Famulok, Ph.D., University of Bonn (Germany), Life & Medical Sciences Institute (LIMES), Max Planck Fellow and corresponding author of the paper. “Our approach creates a platform to use the power of aptamers to dramatically improve the way in which we address the many important health challenges in oncology and beyond.”
About Caris Life Sciences®
Caris Life Sciences® is a leading innovator in molecular science focused on fulfilling the promise of precision medicine through quality and innovation, and the world’s leading immunotherapy diagnostic expert. Caris Molecular Intelligence®, the company’s Comprehensive Genomic Profiling Plus (CGP+) molecular testing service, assesses DNA, RNA and proteins, including microsatellite instability (MSI), tumor mutational burden (TMB) and PD-L1, to reveal a molecular blueprint to guide more precise and personalized treatment decisions. The ADAPT Biotargeting System™, the company’s revolutionary and unbiased profiling platform, is currently being utilized for drug target identification, therapeutic discovery and development, fixed tissue-based companion diagnostics, blood-based cancer screening and biomarker identification. Headquartered in Irving, Texas, Caris Life Sciences offers services throughout the U.S., Europe, Asia and other international markets.
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