Clinical Trials

Trial Description:
This study will evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy in human epidermal growth factor receptor (HER)2-low, hormone receptor (HR) positive breast cancer patients whose disease has progressed on endocrine therapy in the metastatic setting.

Eligibility Requirements:
Key - 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)

Protocol #: 20-536