SBIR-STTR Award

Immune checkpoint inhibitor (ICIs) immunotherapies can result in robust and durable disease control in many advanced malignancies, and their use is transforming cancer care. Despite the growing adoption, however, ICIs are effective in <30% of patients and can cause significant immune-related adverse events (irAEs) in up to ~60% of treated patients. Early determination of which patient will respond and/or develop irAEs remains a great challenge due to the complex interplay of tumor response, toxicity in critical organs, and overall patterns of immune activation. Further complicating their use, ICI costs are high ($100k-$250k annually/patient; total Medicare Part B payment for ICIs in 2018 >$4 billion). A comprehensive assessment of early ICI therapeutic response and toxicity would provide oncologists with timely, actionable information to better balance benefits and risks, improve 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 require manually evaluating a subset of disease sites, which is both laborious and subjective. Immunotherapies' unique mechanism of action often gives rise to novel imaging patterns of tumor response (e.g. pseudoprogression) that cannot be easily resolved by current methods. Disease response, organ toxicity, and lymphoid tissue immune activation are interdependent. Information on all three of these aspects of response 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 for improved overall patient management. To address this unmet need, AIQ Solutions (Madison, WI) proposes to develop ImmunIQ , a software product that provides a comprehensive view of immunotherapy response. Specifically, ImmunIQ will automatically and simultaneously assess: (1) response of all tumor lesions, (2) immune-related toxicities in critical organs, and (3) immune activation. Upon successful completion of Phase I, we will have a functional software prototype. In Phase II, we will clinically validate the platform with outcome and irAE data and develop a prototype ready for commercialization and FDA 510(k) submission.

Public Health Relevance Statement:
Project Narrative Immune checkpoint inhibitor immunotherapies have been transforming the treatment strategies in many advanced malignancies, however despite the growing adoption, it suffers from significant challenges, including low response rate, high incidence of immune-related adverse events, and high treatment costs. A comprehensive assessment of early immunotherapy response would provide oncologists with timely, actionable information to better balance benefits and risks, improve patient outcomes, reduce toxicities and lower healthcare costs. To meet this need, AIQ Solutions proposes to develop ImmunIQ, a software product that automatically analyzes patients' molecular images to provide quantitative and simultaneous data on (1) response of all tumor lesions, (2) immune-related toxicities in critical organs, and (3) immune activation.

Project Terms:
Adoption; Artificial Intelligence; AI system; Computer Reasoning; Machine Intelligence; Bone Marrow; Bone Marrow Reticuloendothelial System; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Colitis; Colon; cost effectiveness; Disease; Disorder; Equilibrium; balance; balance function; Goals; Heart; Immunotherapy; Immune mediated therapy; Immunologically Directed Therapy; immune therapeutic approach; immune therapeutic interventions; immune therapeutic regimens; immune therapeutic strategy; immune therapy; immune-based therapies; immune-based treatments; immuno therapy; Incidence; Intelligence; Lymphoid Tissue; Lymphatic Tissue; Manuals; Methods; Legal patent; Patents; Patients; Research; Computer software; Software; Spleen; Spleen Reticuloendothelial System; Testing; Time; rho; Medicare Part B; Medicare Supplementary Medical Insurance Program; SMI Program; Health Care Costs; Health Costs; Healthcare Costs; health care; Healthcare; Treatment Cost; base; Organ; improved; Site; Clinical; Phase; Evaluation; Lesion; Individual; Measurement; uptake; Oncologist; anti-cancer immunotherapy; anticancer immunotherapy; immune-based cancer therapies; immunotherapy for cancer; immunotherapy of cancer; cancer immunotherapy; Medical Oncologist; Immunological response; host response; immunoresponse; Immune response; tool; Metastatic Cancer; Metastatic Malignant Neoplasm; Disseminated Malignant Neoplasm; Immunes; Immune; Complex; Scanning; Pattern; empowered; Performance; Toxicities; Toxic effect; novel; payment; Benefits and Risks; Pharmacodynamics; response; FDG PET; fluorodeoxyglucose PET; fluorodeoxyglucose positron emission tomography; disease control; disorder control; cancer care; ACT2; AT744.1; Act-2; CCL4; Chemokine (C-C Motif) Ligand 4; Chemokine, CC Motif, Ligand 4; Immune Activation 2; MIP1B; MIP1B1; Macrophage Inflammatory Protein 1-Beta; SCYA4; Small Inducible Cytokine A4; CCL4 gene; Address; Data; Detection; Cancer Patient; Localized Therapy; Local Therapy; Patient outcome; Patient-Centered Outcomes; Patient-Focused Outcomes; Tracer; molecule imaging; molecular imaging; imaging; Image; cost; Outcome; resistant; Resistance; clinical significance; clinically significant; clinical applicability; clinical application; prototype; commercialization; tumor; response to treatment; therapeutic response; treatment response; treatment strategy; Immune Cell Activation; immune activation; therapeutic toxicity; therapy toxicity; Treatment-related toxicity; Checkpoint inhibitor; immune check point inhibitor; Immune checkpoint inhibitor; immune-mediated adverse events; immune-related adverse events; auto-segmentation; automatic segmentation; autosegmentation; automated segmentation

Immune 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.

Public Health Relevance Statement:
Project Narrative Immune 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. In this Phase II SBIR project, AIQ Solutions will build on the successful completion of our Phase I to meet the unique-and currently unmet-needs of immunotherapy patients by providing clinicians with actionable, quantitative, and clinically relevant treatment response information, thus improving clinical out- comes, quality of life and reducing therapy costs.

Project Terms:
Adoption; Algorithms; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Clinical Research; Clinical Study; Clinical Trials; Disease; Disorder; Equilibrium; balance; balance function; Grant; Immunotherapy; Immune mediated therapy; Immunologically Directed Therapy; immune therapeutic approach; immune therapeutic interventions; immune therapeutic regimens; immune therapeutic strategy; immune therapy; immune-based therapies; immune-based treatments; immuno therapy; Lymphoid Tissue; Lymphatic Tissue; Manuals; Methods; Patients; Probability; QOL; Quality of life; Research; ROC Analyses; receiver operating characteristic analyses; receiver operating characteristic curve; ROC Curve; Software; Computer software; Technology; Testing; Time; rho; Measures; Medicare Part B; Medicare Supplementary Medical Insurance Program; SMI Program; Health Care Costs; Health Costs; Healthcare Costs; Healthcare; health care; Treatment Effectiveness; base; Organ; improved; Site; Area; Clinical; Phase; Evaluation; Lesion; insight; Oncologist; radiologist; anti-cancer immunotherapy; anticancer immunotherapy; immune-based cancer therapies; immunotherapy for cancer; immunotherapy of cancer; cancer immunotherapy; Medical Oncologist; Immunological response; host response; immune system response; immunoresponse; Immune response; tool; Metastatic Cancer; Metastatic Malignant Neoplasm; Disseminated Malignant Neoplasm; Life; Immunes; Immune; Complex; Pattern; System; experience; Performance; Toxicities; Toxic effect; payment; Benefits and Risks; Devices; Position; Positioning Attribute; response; disorder control; disease control; cancer care; Effectiveness; Data; predict therapeutic response; predict therapy response; predict treatment response; therapy prediction; treatment prediction; treatment response prediction; Prediction of Response to Therapy; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Validation; Development; developmental; molecular imaging; molecule imaging; Image; imaging; Output; cost; design; designing; Treatment Efficacy; intervention efficacy; therapeutic efficacy; therapy efficacy; Clinical effectiveness; Outcome; prospective; clinically relevant; clinical relevance; clinically significant; clinical significance; usability; prototype; commercialization; tumor; treatment response; response to therapy; response to treatment; therapeutic response; therapy response; clinical decision-making; immune activation; Immune Cell Activation; personalized medicine; personalization of treatment; personalized therapy; personalized treatment; predicting response; prediction of response; predictive response; predictor of response; response prediction; Immune checkpoint inhibitor; Checkpoint inhibitor; immune check point inhibitor; immune-related adverse events; immune-mediated adverse events; financial toxicity