Actively Recruiting
TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd
Led by Ana C Garrido-Castro, MD · Updated on 2025-10-24
357
Participants Needed
11
Research Sites
717 weeks
Total Duration
On this page
Sponsors
A
Ana C Garrido-Castro, MD
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
The purpose of this study is to test the safety and effectiveness of the sequence of two investigational drugs (trastuzumab deruxtecan followed by datopotamab deruxtecan, or datopotamab deruxtecan followed by trastuzumab deruxtecan) to learn whether the treatment works in treating HER2-negative (HER2-low or HER2-0) metastatic breast cancer. The names of the study drugs involved in this study are: * Datopotamab deruxtecan (a type of antibody drug conjugate) * Trastuzumab deruxtecan (a type of antibody drug conjugate)
CONDITIONS
Official Title
TReatment of ADC-Refractory Breast CancEr With Dato-DXd or T-DXd: TRADE DXd
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed invasive breast cancer with unresectable locally advanced or metastatic disease
- Known hormone receptor (ER, PR) and HER2 status from recent pathology in a certified laboratory
- History of HER2-low (IHC 1+ or 2+/ISH non-amplified) or HER2-0 (IHC 0) breast cancer with no HER2-positive history
- Measurable disease according to RECIST 1.1
- Willingness to undergo research tissue biopsies if safely accessible
- For HR-positive breast cancer: progressed on or within 12 months of adjuvant endocrine therapy or received at least one line of endocrine therapy in metastatic setting, and prior CDK4/6 inhibitor use
- Prior chemotherapy in metastatic setting allowed as specified, with no prior topoisomerase I inhibitor except as allowed for ADC2 cohorts
- Discontinued prior biologic or targeted therapy at least 14 days before study start, with resolved toxicities
- Discontinued investigational agents at least 21 days before study start, with resolved toxicities
- Completed prior radiation therapy at least 14 days before study start (7 days for SRS), with resolved toxicities
- History of treated CNS metastases allowed if criteria met
- Patients with new or progressive brain metastases allowed if no immediate CNS treatment needed and asymptomatic
- Use of bisphosphonates or RANK ligand inhibitors allowed
- Age 18 years or older
- ECOG performance status 0-1 (Karnofsky > 60%)
- Adequate organ and marrow function within 2 weeks before treatment
- Resolution of prior treatment toxicities to Grade 1 or baseline
- For T-DXd cohorts, baseline left ventricular ejection fraction (LVEF) ≥ 50%
- Negative pregnancy test for females of childbearing potential within 2 weeks before treatment
- Agreement to use contraception during and after study treatment
- Ability to understand and comply with study procedures and provide informed consent
You will not qualify if you...
- Use of other investigational or study agents for the cancer during the trial
- Prior treatment with chemotherapeutic agents targeting topoisomerase I, except as specified for ADC2 cohorts
- Receipt of live attenuated vaccines within 30 days before study intervention
- Clinically significant corneal disease
- History of severe allergic reactions to trastuzumab deruxtecan, datopotamab deruxtecan, or other monoclonal antibodies
- Major surgery within 2 weeks before study treatment
- Uncontrolled or significant illness that would limit study compliance
- History or current pneumonitis/interstitial lung disease requiring steroids or suspected but unconfirmed cases
- Significant lung diseases or autoimmune disorders affecting lungs
- Corrected QT interval prolongation above specified limits
- Major cardiovascular events or procedures within 6 months before enrollment
- History of second malignancy unless disease-free for at least 3 years or low risk of recurrence
- Uncontrolled HIV or active hepatitis B or C infection
- Active infections including tuberculosis
- Any condition, therapy, or lab abnormality that could interfere with study or is unsafe
- Pregnancy, breastfeeding, or planning pregnancy during the study
AI-Screening
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Trial Site Locations
Total: 11 locations
1
University of Alabama
Birmingham, Alabama, United States, 35294
Actively Recruiting
2
University of San Francisco
San Francisco, California, United States, 94158
Actively Recruiting
3
Yale University Cancer Center
New Haven, Connecticut, United States, 06520
Actively Recruiting
4
Georgetown University Medical Center
Washington D.C., District of Columbia, United States, 20007
Actively Recruiting
5
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Actively Recruiting
6
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Actively Recruiting
7
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02215
Actively Recruiting
8
Montefiore Einstein Comprehensive Cancer Center
The Bronx, New York, United States, 10461
Actively Recruiting
9
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
Actively Recruiting
10
Vanderbilt Cancer Center
Nashville, Tennessee, United States, 37232
Actively Recruiting
11
Baylor College of Medicine
Houston, Texas, United States, 77030
Actively Recruiting
Research Team
A
Ana Garrido-Castro, MD
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
TREATMENT
Number of Arms
8
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