Actively Recruiting
Trastuzumab Deruxtecan vs Endocrine Therapy in Low-HER2 HR+ Advanced Breast Cancer
Led by Yonsei University · Updated on 2025-04-29
141
Participants Needed
1
Research Sites
156 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
"This is a randomized phase II, two-arm, open label, clinical trial to identify LP-WGS ctDNA biomarker to predict T-DXd response in low-HER2 expressing advanced breast cancer patients compared with endocrine therapy. The hormone receptor (HR)-positive low-HER2 advanced breast cancer patients (HER2 IHC 1+ or 2+ \& ISH negative, n=141) who progressed on 1st line endocrine + CDK4/6 inhibitor therapy and received no other systemic therapy for advanced disease are enrolled in this study. Patients are 2:1 randomized to receive T-DXd (5.4mg/kg every 3 weeks, n=94) or endocrine therapy of physician's choice (TPC: fulvestrant, fulvestrant + alpelisib, Fulvestrant + Capivasertib, exemestane, exemestane + everolimus, or tamoxifen, n=47, fulvestrant + alpelisib can be selected in PIK3CA activating mutation positive patients, Fulvestrant + Capivasertib can be selected in 1 or More mutation positive of PIK3CA/AKT1/PTEN). The mandatory baseline archival tissue and ctDNA collection followed by on-treatment ctDNA collection (Cycle 1, Cycle 2, and Cycle 6) and ctDNA collection at progression will be performed in this study. The primary endpoint is PFS after randomization in two treatment arms. The secondary endpoints include overall survival (OS), objective response rate (ORR), progression-free survival (PFS2), adverse events by CTCAE 5.0 criteria, and Quality of life (QoL) measured by EORTC-QLQ-C30 and EORTC-QLQ-BR23 evaluated by questionnaire. The exploratory endpoints are to identify ctDNA biomarkers to predict the TDxd treatment outcome (PFS, OS, ORR) compared to endocrine therapy in HER2-low advanced breast cancer patients and to assess the accordance of genomic profiles between ctDNA and tumor tissues. Predictive biomarkers include copy number aberration (CNA) of gene loci, total ctDNA CNA burden, mutations, ctDNA-based molecular subtype, or HER2 amplicon copy number on LP-WGS ctDNA analysis. The investigator believe this trial will identify crucial circulating biomarkers for T-DXd treatment response in low-HER2 patients, which can guide right patient selection and potential molecular target identification to maximize T-DXd response and to overcome T-DXd resistance.
CONDITIONS
Official Title
Trastuzumab Deruxtecan vs Endocrine Therapy in Low-HER2 HR+ Advanced Breast Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Female patients aged 19 years or older
- Histologically or cytologically confirmed hormone receptor-positive advanced breast cancer
- HER2-low expression status defined as IHC 1+ or 2+ with ISH negative
- No prior history of HER2-positive breast cancer (IHC 3+ or ISH+)
- Progressed on first-line endocrine plus CDK4/6 inhibitor therapy for advanced disease
- No other systemic therapy for advanced breast cancer received after progression
- At least one measurable lesion by RECIST 1.1 criteria
- Adequate tumor tissue sample available for biomarker assessment
- ECOG performance status of 0 or 1
- Pre- or post-menopausal patients; pre-menopausal must receive ovarian suppression during certain endocrine treatments
- Adequate organ and bone marrow function within 14 days before enrollment
- Normal or non-clinically significant ECG and QTc interval ≤470 msec without history of Torsades de pointes
- Left ventricular ejection fraction ≥50% within 28 days before enrollment
- No history of pneumonitis other than radiation pneumonitis
- Signed informed consent provided
- Not pregnant or breastfeeding
- Effective contraception used starting two weeks before treatment and continuing up to seven months after last dose
- No severe or uncontrolled medical conditions that could affect participation
- Completed required washout periods from prior treatments before enrollment
You will not qualify if you...
- Previous treatment with trastuzumab deruxtecan or dato-deruxtecan for advanced breast cancer
- Severe cardiac disease including uncontrolled hypertension, congestive heart failure (NYHA II-IV), recent myocardial infarction within 6 months, or significant arrhythmias
- Active liver or biliary disease except certain stable conditions
- Uncontrolled infections requiring intravenous antibiotics, antivirals, or antifungals
- Receipt of live attenuated vaccine within 30 days before first dose
- Unresolved toxicities from prior anticancer therapy above Grade 1, except stable chronic Grade 2 toxicities
- Significant lung or pulmonary disorders or autoimmune diseases with lung involvement
- History or current interstitial lung disease or pneumonitis not ruled out by imaging
- Presence of spinal cord compression or symptomatic untreated brain metastases
- Significant mental or social conditions that may impair study compliance
- Active primary immunodeficiency, HIV infection, or active hepatitis B or C infection
- Multiple primary cancers within 5 years except certain treated skin or breast cancers
- Inability to swallow oral medications or gastrointestinal disorders interfering with absorption
- Pregnant or breastfeeding women
- Previous allogeneic bone marrow transplant
- Known hypersensitivity to trastuzumab deruxtecan or severe hypersensitivity to other monoclonal antibodies
- Prior treatment with antibody drug conjugates containing exatecan derivative topoisomerase I inhibitors
AI-Screening
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Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Division of Medical Oncology, Yonsei Cancer Center, Yonsei Univ. College of Medicine
Seoul, South Korea
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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