Background
In research hospitals or academic centers, patients are actively engaged to participate in research. However, 80% of cancer patients are not treated in these institutions. This ‘invisible’ majority is under-represented in genomic research,1 leading to bias in the therapeutic pipeline since such research genomic data are the foundation informing drug target selection. This lack of access to research data from the 80% is particularly impactful for immunotherapy, because laboratory models do not recapitulate the complexity and kinetics of human immune systems. Indeed, we had published that longitudinal tumor data is needed to predict immune checkpoint (IO) response.2 Since serial tumor biopsies are impractical, we have now demonstrated that plasma proteomic analysis of serial liquid biopsies from patients before and on treatment can reveal immune regulators driving resistance and define blood-based non-response signatures. But we need to innovate a strategy to engage the invisible 80% outside of academic research institutions to generate such dynamic data in context of real world care for precision therapeutic development.
Methods
To develop precision medicines that can overcome resistance in diverse patient populations, we designed SMART (Serial Molecular Annotation of Response to Therapies), a decentralized research protocol to collect serial liquid biopsies in context of standard-of-care treatment. SMART is enabled by ApricityCare, a remote patient monitoring and management platform staffed by licensed RN assisted by a clinical intelligence co-pilot that codifies guideline-based best practices and standardizes data capture and documentation to ensure high quality clinical annotation (figure 1).
Results
We first sought to demonstrate that ApricityCare enables prospective collection of high quality clinical data for target & biomarker identification. In a subset of 856 patients treated in community practices, ApricityCare captured 28,416 patient-reported outcomes (PRO) data points in addition to 538,679 longitudinal EHR data points. Rosetta assisted symptom evaluations and triage in near real-time reduced recall bias, improved PRO accuracy by 17.5%, and captured 2,161 additional clinician-reported outcome (CRO) data points to generate a more complete view of patients’ status. Building on this, we activated SMART, an IRB approved protocol to collect serial liquid biopsies in context of treatment. Preliminary results of a pilot will be presented.
Conclusions
SMART study has the potential to unlock therapeutic opportunities for the invisible majority. Such dynamic patient data and samples with research consent will advance our understanding of immune-mediated resistance across a broader range of patients and clinical indications, promoting research equity and ensuring inclusive therapeutic pipelines.
References
Chin L. Representation Bias in Genomic Research Data Propagates Structural Inequity in Cancer Care. DIA Global Forum. Oct 2022. https://globalforum.diaglobal.org/issue/october-2022/representation-bias-in-genomic-research-data-propagates-structural-inequity-in-cancer-care/
Chen PL, et al. Analysis of immune signatures in longitudinal tumor samples yields insight into biomarkers of response and mechanisms of resistance to immune checkpoint blockade. Cancer Discov 2016 Aug;6(8):827-37. doi: 10.1158/2159-8290.CD-15-1545. Epub 2016 Jun 14. PMID: 27301722; PMCID: PMC5082984.
Abstract 38 Figure 1
ApricityCare remote patient monitoring and management. As a first-response coverage for in-clinic team, ApricityCare provides 24/7 monitoring, timely triage and virtual care management by nurses supported by a clinical intelligence co-pilot