DESTINY-Breast15: A study recruiting people with HER2-low or HER2 IHC 0 breast cancer that is metastatic or unable to be removed with surgery, to evaluate how safe and effective a targeted therapyA Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer

Inclusion

• Sign and date the main informed consent form
• Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion.

• Pathologically documented Breast Cancer (BC) tumor

  • Is unresectable and/or metastatic.

  • Is hormone receptor-negative or hormone receptor-positive.

    • Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative.
  • Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines1 based on sample collected during Tissue Screening as described above.
  • Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines).
  • Was never previously treated with anti-HER2 therapy in the metastatic setting.

• Has had at least one and up to two prior lines of therapy in the metastatic setting.

  • In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3):

    • Has recurrent disease <2 years from the initiation of adjuvant ET OR
    • Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR
    • Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting
• Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging.
• Participants with brain metastases are allowed in the study. The brain lesion(s) should be small (<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable.
• Has an Eastern Cooperative Oncology Group performance status of 0 or 1.
• Has a minimum life expectancy of 12 weeks at Screening.
• Has a left ventricular ejection fraction ≥50% within 28 days before enrollment.
• Has adequate organ and bone marrow function within 28 days before enrollment.
• Has adequate treatment washout period before enrollment.
• Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.