Study of Trastuzumab Deruxtecan (DS-8201a, T-DXd) versus Investigator's Choice Chemotherapy in HER2-Low, Hormone Receptor Positive Breast Cancer Patients whose Disease has Progressed on Endocrine Therapy in the Metastatic Setting

Prior treatment

• Ineligible for all options in the investigator's choice chemotherapy arm. Patients with contraindications to capecitabine, paclitaxel, and nabpaclitaxel treatment, per local prescribing information, cannot be enrolled
• Active or prior documented ILD/pneumonitis that required steroids or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Concurrent enrolment in another clinical study, unless it is: - an observational (non-interventional) clinical study - during the follow up period of a prior interventional study (prescreening for this study while a patient is on treatment in another clinical study is acceptable)
• Have received a study treatment from a prior interventional study, administered in the last 30 days prior to first dose of this study treatment

Other illness

• Uncontrolled intercurrent illness or significant cardiovascular disease
• Lung-specific intercurrent clinically significant illnesses

Other

• Patients with spinal cord compression or active clinically central nervous system metastasis.

• Patients must be ≥18 years of age.
• Pathologically documented breast cancer that: a. is advanced or metastatic b. Has a history of HER2-low or negative expression, defined as IHC 2+/ISH- or IHC 1+ (ISH- or untested) or IHC 0 (ISH- or untested) c. Has HER2-low expression or HER2 IHC >0 <1+ expression as determined by the central laboratory result from a metastatic setting d. was never previously HER2-positive e. has documented HR+ disease in the metastatic disease setting.
• Has adequate tumor samples for assessment of HER2 status
• Disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy (Progression of disease within 24 months on adjuvant ET is considered a line of therapy) or disease progression on endocrine therapy + CDK4/6 inhibitor within 6 months of starting first line treatment for metastatic disease and considered appropriate for chemotherapy as the next treatment by the investigator.
• No prior chemotherapy for advanced or metastatic breast cancer.
• Has protocol-defined adequate organ and bone marrow function. The most recent results must be used to meet this inclusion criteria