65 Background: Research indicates that most people with cancer are willing to enroll in clinical trials when offered the chance, but only 7% actually participate in cancer treatment trials. Barriers to screening and enrollment include time and effort for providers to screen patients for trials, and lack of awareness of available regional trials. Stakeholders recommended creation of free, automated screening tools and processes integrated into provider workflows, directly interfacing with site electronic health records (EHRs), that would search for regional trial eligibility. The need for such tools was independently identified in a large national survey of oncology providers. Methods: The Blue-button tool was developed to automatically identify relevant, regional clinical trials. A collaboration between ACS CAN and MITRE, a not-for-profit organization working in the public interest, created the tool’s functionality. Clinical workflow and research protocol were developed in collaboration with University of Texas Southwestern Simmons Comprehensive Cancer Center. This SMART-on-FHIR application works within existing EHR systems by automatically extracting and sending limited, deidentified patient data elements to third-party trial matching services via the FHIR mCODE standard, a core set of non-proprietary, open-source structured data elements that establishes minimum standards for the structure and content of oncology data in health records. Potential trial matches within a specified radius of the practice are returned in a standard format using the FHIR Research Study resource. Results: Blue-button extracts limited patient data from EHR and provides it in an interface allowing users to update data before sending to trial matching services. Only non-identifiable information is sent to the external clinical trial matching services, which then return prescreen trial matches for manual review to confirm patient eligibility. Thus, with a few clicks in a medical record, the tool quickly identifies comprehensive trial availability within a specified distance of the patient’s location. When used by providers, Blue-button reduces the manual burden that often prevents consideration of clinical trials and identifies regional opportunities beyond the treating institution. Conclusions: Successful feasibility testing demonstrated the effectiveness of automated regional trial screening as a model. We have launched a clinical trial at two sites to assess the effectiveness of the Blue-button tool with patients in healthcare settings. We expect patient enrollment to continue through part or all of 2025. This trial of the Blue-button tool will provide additional information on provider accessibility and uptake and will demonstrate whether EHR-integrated regional trial screening leads to increased opportunities and enrollment in cancer clinical trials. Clinical trial information: NCT05885880 .