Safety and Efficacy of T-DXd vs. CDK4/6i-based ET as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype

Exclusion criteria

• . Current participation in another therapeutic clinical trial, except other translational studies.
• . Treatment with approved or investigational cancer therapy within 3 weeks prior to initiation of study drug.
• . Treatment with chloroquine/hydroxychloroquine within 14 days prior to initiation of study drug.
• . Have previously been treated with T-DXd and/or fulvestrant. Note: patients who experienced relapse after more than 1 year from completion of fulvestrant are eligible.
• . Patients with advanced, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (including patients with massive uncontrolled effusions \[pleural, pericardial, and/or peritoneal\] and pulmonary lymphangitis).
• . Impairment of gastro-intestinal (GI) function or GI disease that may significantly alter the absorption of CDK4/6i, such as history of GI surgery which may result in intestinal blind loops and patients with clinically significant gastroparesis, short bowel syndrome, unresolved nausea, vomiting, active inflammatory bowel disease, or diarrhea of CTCAE Grade \> 1.
• . Known central nervous system (CNS) involvement (brain metastases and/or leptomeningeal carcinomatosis). Subjects with clinically inactive brain metastases may be included in the study. Subjects with treated brain metastases that are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.
• . Have a concurrent malignancy or malignancy within 5 years of study enrollment with the exception of carcinoma in situ of the cervix and basal cell carcinoma or squamous cell carcinoma of the skin that has been previously treated with curative intent. For other cancers considered to have a low risk of recurrence, discussion with the Sponsor's Medical Monitor is required.