145 Real-time multiomics tumor microenvironment profiling and pan metastatic solid tumor atlas data projection to revolutionize early phase clinical trials
Year: 2024
Type: conference-abstract
Abstract: Background Success of early-phase clinical trials is a significant challenge due to the complexities involved in understanding drug mechanisms of action (MoA) according to each patient’s tumor immune microenvironment (TME) specifities. A deeper and faster understanding of these patients & tumors characteristics beside to MoA along trial enrollment could improve drug development outcomes. In collaboration with Gustave Roussy, the leading cancer center in Europe and one of the top five worldwide, VERACYTE has developed an innovative clinical sample analysis solution, combined with a pan metastatic solid tumor Biopharma Atlas to enable patient data projection. This solution addresses the constraints of short clinical timelines and the need for comprehensive multi-omics data reporting. Methods and Results The solution profiles samples from FFPE tumor core biopsies using transcriptomic, genomic and proteomic analyses. Our VERACYTE Biopharma ATLAS database was obtained from retrospective patient’s metastatic tumor samples (N=200) across various metastatic cancer indications representative from patients enrolled in phase 1 trials (PEMBIB_NCT02856425, PREMIS_NCT03984318, STING). Thanks to this Atlas database, we could demonstrate our ability to provide an in-depth TME characterization in a prospective clinical trial cohort. The analysis covers the impact of treatment on immune cell ratios, including the proportions of macrophages (distinguishing between pro-inflammatory and pro-tumoral types) and T cells (examining infiltration, activation, exhaustion). Additionally, this includes analyzing druggable target and cytokine expression, enriched pathways, Immunoscore-IC, Immunosign and genomic alterations such as mutations, copy number alterations, tumor mutational burden and microsatellite instability. Our flexible model enables implementation of innovative additional analysis. Conclusions Our data indicate that this real-time comprehensive analysis can reveal critical tumor insights. Understanding the interaction between oncogenic alterations and immune cell infiltrations and functions can: Predict responses to immunotherapy by specifically focusing on pre-treatment biopsies for precision medicine. Enhance our understanding of the TME, facilitating better alignment with drug mechanisms of action Guide enrollment in early trials or precision medicine trials. The ability to quickly assess these parameters in a clinically relevant timeframe represents a significant advancement, offering potential benefits for both patient outcomes and the efficiency of clinical trials. This real-time approach not only enhances our understanding of the TME but also supports more informed decisions regarding trial enrollment, ultimately aiming to improve patient care and pharmaceutical strategies. Overall, this innovative approach promises to significantly improve the design and outcomes of early-phase clinical trials. Trial Registration PEMBIB_NCT02856425, PREMIS_NCT03984318.
Institutions: Institut Gustave Roussy, Dana-Farber Cancer Institute
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4404065578