AUTOMATED PLASMA EV-PDL1 ANALYSIS FOR CANCER IMMUNOTHERAPY - ABSTRACT CHALLENGES. THERE ARE OVER 4000 CLINICAL TRIALS TESTING ANTI-PD1/PD-L1 IMMUNE CHECKPOINT INHIBITORS (ICI), EITHER ALONE OR IN COMBINATION WITH OTHER THERAPIES. WHILE MANY PATIENTS BENEFIT, THE VAST AMOUNT DO NOT, ALL AT A CONSIDERABLE COST. THE MOST VALIDATED AND FDA-APPROVED BIOMARKER TO GUIDE PATIENT SELECTION IS THROUGH IMMUNOHISTOCHEMICAL (IHC) STAINING AND SCORING OF TISSUE BIOPSIES FOR PD-L1 (E.G. TUMOR PROPORTION SCORE, TPS). UNFORTUNATELY, TPS IS AN IMPERFECT BIOMARKER: I) IT REQUIRES SURGICAL OR IMAGE GUIDED TISSUE BIOPSY WHICH IS SOMETIMES DIFFICULT TO PERFORM; II) THE SITE AND TIMING OF TISSUE ACQUISITION AND STAINING PROTOCOLS CAN INFLUENCE THE ACCURACY OF TPS; III) IHC TAKES DAYS TO PROCESS, DELAYING TREATMENT; IV) MANY TPS-POSITIVE PATIENTS DO NOT RESPOND TO ICI TREATMENT; AND V) TPS CAN CHANGE DURING CHEMO, TARGETED AND ICI THERAPIES. PHASE I GOALS. ACCURE HEALTH PROPOSES TO EXPLORE AN ALTERNATIVE APPROACH: CIRCULATING PD-L1 BIOMARKER ASSAY BASED ON TECHNOLOGY-INTEGRATED MAGNETO-ELECTRONIC SENSING (TIMES) OF EXTRACELLULAR VESICLES (EVS). SUPPORTED BY PROMISING CLINICAL DATA, WE HYPOTHESIZE THAT CIRCULATING EV ANALYSIS INTEGRATING PD-L1 EXPRESSION FROM PRIMARY AND METASTATIC LESIONS CAN BE A MORE COMPREHENSIVE MARKER. WE PROPOSE TWO SPECIFIC AIMS. AIM 1. DEVELOP AN AUTOMATED TIMES ASSAY TO ANALYZE PAN EV-PDL1 AND CELL TYPE-SPECIFIC EV-PDL1. AIM 2. ESTABLISH TIMES EV-PDL1 SCORES AND CORRELATE WITH TPS. WE ENVISION THE AUTOMATED TIMES EV-PDL1 ASSAY AND INTEGRATED SCORES CAN BE UTILIZED IN CLINICAL TRIALS TESTING ANTI-PD1/PD-L1 MONO- OR COMBINATION THERAPIES. IT CAN PROVIDE A FASTER AND MORE RELIABLE SOLUTION FOR EVALUATING TREATMENT RESPONSE, AND HELP ACCELERATE REGULATORY DECISION-MAKING.