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.
Eligible patients will be those patients who have had disease progression on at least 2 previous lines of endocrine therapies given for the treatment of metastatic disease or disease progression within 6 months of starting first line treatment for metastatic disease with an endocrine therapy combined with a CDK4/6 inhibitor. All patients must have historically confirmed HR positive (either estrogen receptor and/or progesterone receptor positive), HER2-low (defined as IHC2+/ISH- and IHC 1+) or HER2 IHC >0 <1+ expression, as determined by central laboratory testing results, advanced or metastatic breast cancer.
The study aims to evaluate the efficacy, safety and tolerability of trastuzumab deruxtecan compared with investigator's choice chemotherapy. This study aims to see if trastuzumab deruxtecan allows patients to live longer without the cancer getting worse, or simply to live longer, compared to patients receiving standard of care chemotherapy. This study is also looking to see how the treatment and the cancer affects patients' quality of life.
- Patients must be ≥18 years of age
- Pathologically documented breast cancer that:
- is advanced or metastatic
- 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)
- has HER2-low or HER2 IHC 0 expression must be confirmed by central laboratory testing to have HER2-low expression or HER2 IHC >0 <1+ expression, respectively.
- was never previously HER2-positive
- 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:
- disease progression within 6 months of starting first line metastatic treatment with an endocrine therapy combined with a CDK4/6 inhibitor or
- 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
- Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline.