Study of Trastuzumab Deruxtecan (T-DXd) vs Investigator's Choice Chemotherapy in HER2-low, Hormone Receptor Positive, Metastatic Breast Cancer

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 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

• Must have either:

  1. disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
  2. disease progression on at least 2 previous lines of endocrine therapy with or without a targeted therapy in the metastatic setting. Of note with regards to the ≥2 lines of previous ET requirement: disease recurrence while on the first 24 months of starting adjuvant ET, will be considered a line of therapy; these patients will only require 1 line of ET in the metastatic setting.

• Has protocol-defined adequate organ and bone marrow function

Key

Exclusion Criteria

• Ineligible for all options in the investigator's choice chemotherapy arm
• Lung-specific intercurrent clinically significant illnesses
• Uncontrolled or significant cardiovascular disease or infection
• Prior documented interstitial lung disease (ILD)/ pneumonitis that required steroids, current ILD/ pneumonitis, or suspected ILD/ pneumonitis that cannot be ruled out by imaging at screening.
• Patients with spinal cord compression or clinically active central nervous system metastases
• Prior randomization or treatment in a previous trastuzumab deruxtecan study regardless of treatment arm assignment
• 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)