Tests trastuzumab deruxtecan in breast cancer with low or no HER2
Tests trastuzumab deruxtecan in adults with HER2-low or HER2-0 advanced breast cancer.
Plain-language title generated from the registry record
Registry title: Trastuzumab Deruxtecan (T-DXd) in Patients Who Have Hormone Receptor-negative and Hormone Receptor-positive HER2-low or HER2 IHC 0 Metastatic Breast Cancer
Key facts
- Where
- Cork, Dublin 4, Dublin 7, Dublin 8, Dublin 9, and Galway, IrelandSee the 6 sites
- Phase
- Phase 3
AI summary: who the study is looking for
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with breast cancer that cannot be removed by surgery or has spread, and that is HER2-low or HER2 IHC 0. Both hormone receptor-negative and hormone receptor-positive cancers can join.
- Age
- 18 years or older
- Sex
- All sexes can join.
- Disease stage
- Breast cancer that cannot be removed by surgery and/or has spread (metastatic). HER2 status is HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2 IHC 0. At least one measurable lesion on CT or MRI. Small, untreated brain metastases without symptoms are allowed.
- Earlier treatment
- Must have had at least one and up to two earlier lines of treatment for spread disease. Must never have had anti-HER2 therapy for spread disease. Must not have had an antibody drug conjugate (ADC) before. Hormone receptor-positive HER2-low cancer has extra rules on earlier hormone therapy and CDK4/6 inhibitor treatment.
- Biomarker or test result
- HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) or HER2 IHC 0, confirmed on a tumor sample taken at screening. The cancer must never have been HER2-positive (IHC 3+ or IHC 2+/ISH+). Hormone receptor status (negative or positive) must be documented.
Main reasons for not taking part
- Earlier treatment with an antibody drug conjugate (ADC)
- History of interstitial lung disease or pneumonitis that needed steroids, or current lung inflammation of this kind
- Uncontrolled or significant heart disease
- Spinal cord compression or active brain or spinal cord metastases
- Pregnant or breastfeeding, or planning to become pregnant
Read by machine on 12 November 2026.
Where in Ireland
- Cork University HospitalCork, IrelandNo longer taking part
- St Vincent's University HospitalDublin 4, IrelandNo longer taking part
- Mater Misericordiae University HospitalDublin 7, IrelandNo longer taking part
- St James's HospitalDublin 8, IrelandNo longer taking part
- Beaumont HospitalDublin 9, IrelandNo longer taking part
- University Hospital GalwayGalway, IrelandNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorTrial details
- Who runs it
- Daiichi Sankyo
- Trial code
- NCT05950945EU 2023-505616-38-00
- Record updated
- 12 June 2026
- Original description
This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor [HR]-negative and HR-positive) unresectable and/or metastatic breast cancer.Read full original descriptionShow less
A Phase 3b, Multicenter, Global, Interventional, Open-label Study of Trastuzumab Deruxtecan (T-DXd), an Anti-HER2-Antibody Drug Conjugate (ADC), in Subjects Who Have Unresectable and/or Metastatic HER2-low or HER2 Immunohistochemistry (IHC) 0 Breast Cancer (DESTINY-Breast15)
This study will evaluate the safety and efficacy of trastuzumab deruxtecan (T-DXd) in participants with human epidermal growth factor receptor 2 (HER2)-low or HER2 immunohistochemistry (IHC) 0 (who are both hormone receptor [HR]-negative and HR-positive) unresectable and/or metastatic breast cancer.
Inclusion: Sign and date the main informed consent form; Must agree to provide a newly obtained or archival baseline biopsy from primary and/or metastatic lesion; Pathologically documented Breast Cancer (BC) tumor; Is unresectable and/or metastatic; Is hormone receptor-negative or hormone receptor-positive; Must include percentage of positively stained cells to characterize if hormone receptor-positive or -negative; Has confirmed HER2 IHC 1+ or IHC 2+/ISH- (HER2-low) status or HER2 IHC 0 status as determined according to ASCO CAP 2018 guidelines1 based on sample collected during Tissue Screening as described above; Was never previously HER2-positive (IHC 3+ or IHC 2+/ISH+) on prior pathology testing (per ASCO CAP guidelines); Was never previously treated with anti-HER2 therapy in the metastatic setting; Has had at least one and up to two prior lines of therapy in the metastatic setting; In participants with hormone receptor-positive HER2-low metastatic BC (Cohort 3):; Has recurrent disease <2 years from the initiation of adjuvant ET OR; Has disease progression on CDK4/6 inhibitor-based regimen within 12 months of completion of adjuvant therapy with a CDK4/6 inhibitor OR; Has disease progression within the first 12 months of CDK4/6 in the first line metastatic setting; Presence of at least one measurable lesion based on computed tomography or magnetic resonance imaging; Participants with brain metastases are allowed in the study. The brain lesion(s) should be small (<2 cm), untreated, asymptomatic, not requiring urgent medical intervention, and are asymptomatic and clinically stable; Has an Eastern Cooperative Oncology Group performance status of 0 or 1; Has a minimum life expectancy of 12 weeks at Screening; Has a left ventricular ejection fraction ≥50% within 28 days before enrollment; Has adequate organ and bone marrow function within 28 days before enrollment; Has adequate treatment washout period before enrollment; Male and female subjects of reproductive/childbearing potential must agree to use a highly effective form of contraception.
Exclusion: Prior treatment with an antibody drug conjugate (ADC); Has history of receiving a live, attenuated vaccine (messenger RNA and replication-deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first exposure to study drug; Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤1 or baseline; Prior complete pneumonectomy; Uncontrolled or significant cardiovascular disease; Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening; Has multiple primary malignancies within 3 years, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, other solid tumors curatively treated, or contralateral BC; Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients in the drug product; Has a history of severe hypersensitivity reactions to other monoclonal antibodies; Has an uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals; Active primary immunodeficiency, known uncontrolled active human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection; Lung-specific intercurrent clinically significant illnesses; Any autoimmune, connective tissue, or inflammatory disorders; Has a corrected QT interval prolongation; Has spinal cord compression or clinically active central nervous system metastases; Is pregnant or breastfeeding or planning to become pregnant.