Comprehensive Assessment of Cancer Immunotherapy Response

Project SummaryImmune checkpoint inhibitors (ICIs) are transforming cancer care resulting in robust and durable disease control in many advanced malignancies. Despite their growing adoption, however, ICIs are only effective for less than 30% of patients and can cause significant immune-related adverse events (irAE) in up to 60% of treated patients. Early determination of which patient will respond and/or develop irAE remains a great chal- lenge due to the complex interplay of tumor response, toxicity in critical organs, and overall patterns of immune activation. Critically missing is a comprehensive assessment of therapeutic response and prediction of toxicity that would provide oncologists with timely, actionable information to optimally balance benefits and risks, im- prove patient outcomes, reduce toxicities, and lower healthcare costs.Molecular imaging is an invaluable tool for assessing spatial and temporal changes in tumors, damage to critical organs and immune activation during immunotherapies. Unfortunately, current assessments rely on manual evaluation of a subset of disease sites, which is both laborious and subjective, particularly in cases of metastatic disease. Furthermore, the unique mechanism of action of ICIs often gives rise to specific imaging patterns of tumor response (e.g, pseudoprogression) that cannot be easily resolved using current methods. Disease response, organ toxicity, and lymphoid tissue immune activation are interdependent; information on all three factors must be known to capture the complete landscape of immunotherapy response. The status quo in assessing response not only fails to fully extract clinically significant information from the imaging data, but also provides very limited information to medical oncologists to optimize patient management.In this Phase II SBIR project, AIQ Solutions will build on the successful completion of our Phase I project to bridge the gap between clinical need and existing products. Based on our Phase I results, our software will meet the unique–and currently unmet–needs of immunotherapy patients with metastatic cancer by providing a comprehensive analysis of immunotherapy response including: (1) quantify treatment effectiveness in all lesions, (2) quantify immune-related toxicities in critical organs, (3) calculate the probability of achieving opti- mal overall clinical effectiveness, and (4) calculate the probability of irAE. To do this, we propose the following aims and milestones. (1): Complete development, refine performance, and validate the TRAQinform Immuno technology. (2) Perform usability assessment of the TRAQinform Immuno technology. (3) Evaluate actionable information output from the TRAQinform Immuno technology in a prospective, non-interventional clinical study. Upon successful completion of the SBIR Phase II, we will have completed development and basic validation of TRAQinform Immuno technology. Additionally, we will be positioned to submit for FDA clearance and to launch the prospective clinical trials that will lead to commercialization of the TRAQinform Immuno technology as a platform to be used by clinicians for the comprehensive management of immunotherapy-treated patients.