Mark R. Miglarese
Caris Life Sciences, USA
Title: ADAPT Biotargeting SystemTM: A next generation poly-ligand profiling approach for precision medicine
Biography
Biography: Mark R. Miglarese
Abstract
Despite significant advances in precision medicine in oncology, the performance of predictive biomarkers and companion diagnostics remains profoundly suboptimal. Clinical benefit from specific cancer therapies is determined by subtle differences in tumor system biology that are inherently difficult to access. Accordingly, highly multiplexed methods are required to evaluate these perturbations. We developed the ADAPT Biotargeting SystemTM which employs aptamer-based polyligand profiling to distinguish a wide range of complex yet subtle phenotypes including response to molecularly targeted therapy. We show that the ADAPT Biotargeting SystemTM can distinguish tumor tissues from breast cancer patients who either did or did not derive benefit from HER2-targeted trastuzumab-based regimens. Test performance was assessed by calculating AUC values from ROC curves and by generating Kaplan-Meier plots using time to next therapy (TTNT) as a surrogate measure of clinical benefit. ADAPTTM test-positive patients showed improved clinical outcomes from trastuzumab-based treatment (median TTNT of 429 days versus 129 days for test-negative patients [n=61, HR=0.384, p=0.001]). Interestingly, the ADAPT test also identified patients who received significant clinical benefit from trastuzumab-based therapy despite having HER2-/low scores by IHC (median TTNT of 421 days versus 199 days [n=23, HR=0.119, p=0.001] for chemotherapy alone). Thus, the ADAPT Biotargeting SystemTM has the potential to identify the patients who would benefit from trastuzumab-containing regimens despite standard HER2 testing suggesting otherwise. We are currently building a number of ADAPT assays to improve upon suboptimal predictive biomarkers currently used for a wide range of cancer therapies.