Abstract PO2-19-10: CAPItello-292 Phase 3: An open-label, randomized study of capivasertib, fulvestrant, and investigator’s choice of CDK4/6 inhibitor (palbociclib or ribociclib) in HR+/HER2– advanced breast cancer

作者：Hope S. Rugo, Barbara Pistilli, Julie Collins, Celina M. D’Cruz, Christopher Gresty, Roberto Sommavilla, Dhivya R. Sudhan, Claire Miller, Ju-Young Ha, Patrick Neven · 发表于：Cancer Research · 年份：2024 · DOI：10.1158/1538-7445.sabcs23-po2-19-10 · 被引用次数：6 · 研究领域：Advanced Breast Cancer Therapies、Breast Cancer Treatment Studies、HER2/EGFR in Cancer Research

Abstract Background: Overcoming resistance to endocrine therapy in advanced breast cancer (ABC) is a major challenge, and there remains an unmet need for safe and efficacious treatment options. AKT pathway activation is implicated in resistance to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) ABC. In the Phase 3 CAPItello-291 study, capivasertib (a potent inhibitor of all three AKT isoforms) plus fulvestrant significantly improved progression-free survival (PFS) versus fulvestrant in patients with aromatase inhibitor-resistant HR+/HER2– ABC. Simultaneous inhibition of the AKT and CDK4/6 pathways may delay CDK4/6 inhibitor resistance or re-sensitize tumors to endocrine therapy plus CDK4/6 inhibitors, leading to improved clinical outcomes. CAPItello-292 is an ongoing Phase 1b/3 study examining the efficacy and safety of adding capivasertib to fulvestrant plus a CDK4/6 inhibitor in HR+/HER2– ABC. Phase 1b has previously confirmed the recommended Phase 3 dose (RP3D) in combination with palbociclib to be tolerable with preliminary signals of clinical activity; determination of the RP3D in combination with ribociclib is currently being explored. Trial design: The Phase 3 component of CAPItello-292 is an open-label, randomized study assessing the efficacy of the addition of capivasertib to fulvestrant and the investigator’s choice of CDK4/6 inhibitors (eit...