Abstract PS4-09-08: Expanding Diversity through Innovation: Development of the I-SPY ACCESS Initiative for the I-SPY2.2 and DCIS RECAST Clinical Trials

Abstract Introduction Cancer clinical trials have historically faced challenges in achieving fully representative trial population, particularly in terms of including patients from diverse ethnic and racial groups, those with low socioeconomic status, and those living in rural regions. This has contributed to inequities in access to novel therapeutic options. Background The I-SPY adaptive platform trials have prioritized diversity since inception, consistently enrolling in >10% of trial patients being Black and/or Hispanic individuals. The majority of participating institutions in the I-SPY 2.2 study are academic or large well-resourced health systems. In 2023, the I-SPY ACCESS (Achieving Cancer Clinical Trial Equity in Socioeconomically Diverse Sites) Initiative was launched to enhance representation by engaging and involving nontraditional trial sites- such as safety-net hospitals, community cancer centers, and rural cancer centers- that serve historically excluded patient populations. Methods The I-SPY ACCESS Initiative offers customized and personalized tailored support to under-resourced sites. This includes comprehensive feasibility and readiness assessments, onboarding guidance, enhanced site-specific training, centralized institutional review board (IRB) navigation, site peer mentorship, and educational materials for both patient and provider. Additionally, patients gain access to I-SPY advocate peer trial navigators. Sites are provided culturally responsive patient education tools- including multilingual brochures, a dedicated patient website, and content co-developed with community partners. A Clinical Trial Navigator supports both patients and sites, helping to locate logistical, social, and trial specific resources.Tools such as virtual Clinical Research Coordinators (vCRC's) and OneSource technology are deployed strategically based on assessed site need and resource availability. OneSource is an innovative platform that enables direct extraction of clinical data from electronic health records into trial databases, reducing site workload and improving data quality. Funding models are currently being explored to extend OneSource and vCRC services across more ACCESS sites. In the future, there are plans to pilot financial navigation services and integrative care resources for all patients enrolled in I-SPY with particular focus on those enrolled at ACCESS sites. Results and Progress As of June 2025, seven sites have been assessed as ACCESS sites for I-SPY 2.2, with two sites having successfully completed activation and currently enrolling participants. Beginning in mid-2024, one DCIS RECAST ACCESS site has been activated and 11 additional sites are in the onboarding process. The modest pace of I-SPY 2.2 activation reflects the complexity and operational demands associated with resource-intensive platform trial. In contrast, the DCIS RECAST protocol was designed with a lower burden, facilitating easier implementation by under-resourced sites, reflected by increased interest in the study among ACCESS sites. The ACCESS framework is being explored for potential future application in the Pre I-SPY Phase 1 platform trial, particularly considering the historical underrepresentation of such sites in the early-phase clinical research. Conclusion and Future Goals The I-SPY ACCESS initiative demonstrates that investing in thoughtful, innovative, and effective means for trial delivery, as well as incorporating community-based support, can strengthen representation in complex, adaptive breast cancer trials. The initiative offers a flexible, equity-driven framework that is impactful now and scalable for future innovation in oncology research. Citation Format: S. L. Horton, D. A. Idossa, K. C. Hewitt, J. Perlmutter, L. Van't Veer, N. Hylton, A. Borowsky, F. Symmans, D. Yee, C. Yau, P. Pohlmann, J. Boughey, L. Esserman. Expanding Diversity through Innovation: Development of the I-SPY ACCESS Initiative for the I-SPY2.2 and DCIS RECAST Clinical Trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-09-08.