A Phase 3, Randomized, Multi-center, Open-label Study of Trastuzumab Deruxtecan (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 (DESTINY-Breast06)

Key Inclusion Criteria:
• Patients must be >=18 years of age.
• Pathologically documented breast cancer that:
1. is advanced or metastatic
2. has a history of HER2-low or negative expression by local test, defined as
IHC 2+/ISH- or IHC 1+ (ISH- or untested) or HER2 IHC 0 (ISH- or
untested)
3. has HER2-low or HER2 IHC >0 <1+ expression as determined by the central
laboratory result established on a tissue sample taken in the metastatic
disease setting
4. was never previously HER2-positive
5. is documented HR+ disease in the metastatic setting.
• No prior chemotherapy for advanced or metastatic breast cancer.
• Has adequate tumor samples for assessment of HER2 status
• 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 OR
• 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)
• Has protocol-defined adequate organ and bone marrow function.

Key Exclusion Criteria:
• Ineligible for all options in the investigator*s choice chemotherapy arm
• Uncontrolled intercurrent illness or significant cardiovascular disease
• Active or prior documented ILD/pneumonitis or suspected ILD/pneumonitis that
cannot be ruled out by imaging at screening
• Lung-specific intercurrent clinically significant illnesses
• Patients with spinal cord compression or clinically central nervous system
metastasis.