Rationale and Trial Design of DAWNA‐FES Trial: Single‐Arm Phase II Study of Endocrine Therapy With Dalpiciclib After Progression on CDK4/6 Inhibition Based on 18 FFES PET/CT in Patients With HR+/HER2− Advanced Breast Cancer

Background: F]FES) PET/CT, a novel imaging modality targeting estrogen receptors (ER), enables non-invasive, whole-body assessment of ER expression in metastatic lesions, offering a personalized approach to treatment selection. Methods: F]FES-positive lesion will be enrolled. Participants will receive dalpiciclib combined with ET as determined by the treating physician. The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Discussion: F]FES PET/CT-guided patient selection, including standardized imaging workflows and multidisciplinary implementation in routine clinical research. Positive outcomes may support a personalized, imaging-guided strategy to prolong disease control after prior CDK4/6 inhibitor progression. Ethical Approval and Trial Registration: Approved by the Ethics Committee of Peking Union Medical College Hospital (Approval number: K3629); registered at ClinicalTrials. gov (NCT05613270).