OPTIMA: Oncology Precision Trials using Individualized Model Avatars

About This Grant

OPTIMA: SUMMARY Although in vitro and in silico tissue models have been developed to predict cancer patient responses, they have yet to significantly influence clinical decision-making. This proposal seeks to integrate these models into clinical practice by establishing them as reliable tools for guiding treatment decisions as well as patient selection for clinical trials. However, several key challenges must be addressed, including the need for standardization and clinical validation of predictive capabilities. Leveraging ongoing therapeutic clinical trials provides a unique opportunity to overcome these challenges by facilitating validation and iterative standardization without requiring prohibitive upfront costs. The integration of combinatorial New Approach Methodologies (NAMs) into clinical trials offers a promising strategy to advance these predictive models for real-world applications. The major goal of this project is to develop clinical-grade combinatorial NAM assays to inform treatment decisions for colorectal cancer (CRC) patients. Taking advantage of three innovative clinical trials recently launched at MD Anderson, the study will evaluate the ability of combinatorial NAMs to predict patient responses in a timely, reliable, and reproducible manner. Three core methodologies— in vitro micro-organospheres (MOSs) and in silico DL-REFLECT and VirtualCellTherapy—will be validated using clinical samples and patient outcomes. Specifically, the project will develop combinatorial NAM assays to (1) improve treatment selection and outcomes for metastatic CRC (mCRC) patients after first line treatment, (2) accelerate therapeutic development for patients with minimal residual disease (MRD) who currently lack any treatment modalities or guidelines, and (3) enable better patient selection for CAR-NK therapies to succeed in solid tumors. After the initial standardization and clinical validation of the NAM assays, the Emerging Diagnostics Center (EDC) in the Division of Pathology and Laboratory Medicine (DPLM) at MD Anderson will partake in the effort to develop them into College of American Pathologists (CAP)-accredited, laboratory developed tests (LDTs). The EDC will provide these combinatorial NAM assays to support clinical treatment decisions and patient selection for clinical trials at MD Anderson as well as provide training and dessemination support. Beyond assay development, the project aims to advance next-generation NAMs and expand workforce development. The project will explore new methodologies, such as extracellular matrix (ECM)-free 2D organoids for improved assay speed and cost-efficiency, micro-iPSC-organoids for toxicity assessments, and agent-based models for evaluating cell therapy dynamics. These innovations could be integrated into existing NAMs to enhance predictive accuracy and expand clinical applications. The project also aims to incorporate NAM education into biomedical curricula, to form regional partnerships for expanded outreach, and provide hands-on training for researchers, clinicians, and regulatory professionals.