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


About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

- 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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Karthik Giridhar, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office


Jacksonville, Fla.

Mayo Clinic principal investigator

Pooja Advani, M.B.B.S., M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Brenda Ernst, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information


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