Clinical Trials

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 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)

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 8/23/22. Questions regarding updates should be directed to the study team contact.