Monday, October 7, 2024
10/7/2024
SUMMARY Defining who is likely to respond to cancer immunotherapy and who may not benefit, due to primary/secondary resistance or adverse events, is of critical interest for improving immuno-oncology (IO) treatments. Most clinical trials of novel combinations either fail to include any support for complex correlative biomarker discovery, often due to costs of specimen collection and assays, or are performed in an idiosyncratic manner, making non- standardized data difficult to integrate as part of a larger repository. There is a need to go beyond just PD-L1 tissue expression and tumor mutation burden as FDA-approved yet imperfect predictors of immune checkpoint blockade, by generating high-dimensional datasets that characterize the tumor immune microenvironment, systemic circulating immune and proteomic markers from blood, and host-level immune fitness information (microbiome). The Cancer Immune Monitoring and Analysis Centers, Cancer Immunologic Data Commons, and Partnership for Accelerating Cancer Therapies (CIMAC-CIDC-PACT) is a Cancer Moonshot-funded network that brings together laboratory, clinical, and computational scientists, administrators, and regulatory specialists from four institutions, Icahn School of Medicine at Mount Sinai (ISMMS), MD Anderson Cancer Center (MDACC), Dana-Farber Cancer Institute (DFCI), and Stanford University. Our unprecedented, coordinated effort to conduct IO clinical trial correlative studies and define new candidate biomarkers to improve immunotherapy had resulted in 37 clinical trials selected in the first funding period, with ongoing datasets resulted for 17 of them. This was achieved using rigorously assessed SOPs and processes from trial selection to data sharing. We propose to continue and expand these efforts as follows: A set of well-established, harmonized, high-dimensional tumor and blood-based assays will be applied to all newly selected trials, with the aim of evaluating and validating novel biomarker of treatment, clinical response, and/or adverse events (Aim 1). To spur innovation and increase granularity of our understanding of mechanism of action, high-tech yet validated single cell and spatial transcriptomic technologies as well as other omics will be proposed in exceptional patients for unbiased phenotyping, tissue composition, architectural organization, and immune profiling (Aim 2). The resulting unified data repository will be mined to define multi-omic and cross-trial markers, through biostatistical and computational innovative design to integrate datasets from various assays into higher analytical archetypes across studies (Aim 3). Together, our network is at the forefront of immune monitoring standards, by balancing innovation with reproducibility, to comprehensively assess biomarkers and strive for precision cancer treatment. We are poised to create an unparalleled resource of harmonized, clinically annotated datasets shared with the public that will establish best practice guidelines with the research community. Through rigorous implementation of state-of-the-art, cross-compared platforms, the CIMAC-CIDC initiative aims to accelerate identification of clinically actionable biomarkers of response, resistance, and adverse events, and define mechanisms at play.
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