A Study of Trastuzumab Deruxtecan (T-DXd) Versus Trastuzumab Emtansine (T-DM1) in High-risk HER2-positive Participants With Residual Invasive Breast Cancer Following Neoadjuvant Therapy (DESTINY-Breast05)

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Adults ≥18 years old (local regulatory requirements will apply if the legal age of consent for study participation is >18 years old).

Pathologically documented HER2-positive breast cancer (BC):

HER2-positive expression defined as an immunohistochemistry (IHC) score of 3+ and/or positive by in situ hybridization (ISH) confirmed prior to study randomization.Histologically confirmed invasive breast carcinoma. Clinical stage at disease presentation: T1-4, N0-3, M0; patients presenting with T1N0 tumors are not eligible.

Pathologic evidence of residual invasive carcinoma in the breast and/or axillary lymph nodes following completion of neoadjuvant therapy meeting one of the following high-risk criteria:

Inoperable breast cancer at presentation (prior to neoadjuvant therapy), defined as clinical stages T4, N0-3, M0 or T1-3, N2-3, M0.Operable at presentation, defined as clinical stages T1-3,N0-1,M0, with axillary node positive disease (ypN1-3) following neoadjuvant therapy.

Completion of neoadjuvant systemic therapy, including taxane-based chemotherapy and HER2-directed treatment prior to surgery.

Systemic therapy must consist of at least 6 cycles of neoadjuvant therapy with a total duration of at least 16 weeks, including at least 9 weeks of trastuzumab (± pertuzumab) and at least 9 weeks of taxane-based chemotherapy to be completed prior to surgery. Patients may have received an anthracycline as part of neoadjuvant therapy in addition to taxane chemotherapy.Adequate excision as confirmed per medical records: surgical removal of all clinically evident disease in the breast and axillary lymph nodes. An interval of no more than 12 weeks between the date of last surgery and the date of randomization. Known hormone receptor (HR) status, per local laboratory assessment, as defined by ASCO-CAP guidelines (≥1%): HR positive status defined by either positive estrogen receptor (ER) and/or positive progesterone receptor (PR).

status. HR-negative status defined by both known negative ER and known negative PR.

Left ventricular ejection fraction (LVEF) ≥50% within 28 days prior to randomization.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at Screening. Has adequate organ function within 14 days before randomization.

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