Trastuzumab Deruxtecan vs Endocrine Therapy in Low-HER2 HR+ Advanced Breast Cancer
This is not medical advice. AI-assisted translation — inaccuracies may occur. Always verify the original and consult your oncologist before taking any steps.
About the trial
"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.
Original English text from ClinicalTrials.gov
Who can (and can't) join
✓ Qualifies
- •Potwierdzona histologicznie lub cytologicznie rak piersi wrażliwy na hormony, zaawansowany, z nawrotem, przerzutami lub niemożliwością do usunięcia chirurgicznego
- •Niska ekspresja HER2 (IHC 2+/ISH- lub IHC 1+) potwierdzona badaniem zgodnym ze standardami ASCO/CAP
- •Brak wcześniejszej historii raka piersi z wysoką ekspresją HER2 (IHC 3+ lub ISH+)
- •Progresja choroby po pierwszej linii leczenia inhibitorem endokrynnym i inhibitorem CDK4/6 (bez innej chemioterapii na tego etapu)
- •Wiek co najmniej 19 lat
- •Radiologiczny lub obiektywny dowód progresji choroby przed rozpoczęciem badania
- •Co najmniej jedno zmierzalne zognisko choroby nie poddane wcześniej radioterapii
- •Prawidłowa funkcja narządów wewnętrznych i szpiku kostnego (odpowiednie wartości hemoglobiny, trombocytów, funkcji nerek i wątroby)
Simplified criteria — AI translation
Trial details
- Minimum age
- 19 Years
- Last updated (source)
- April 29, 2025
- Sex
- Female only
Therapies / drugs in trial
Locations (1)
Division of Medical Oncology, Yonsei Cancer Center, Yonsei Univ. College of Medicine
Seoul, South Korea
Trial contact
Joohyuk sohn
Contact information from ClinicalTrials.gov. Contact in English.
Share this trial
Data from ClinicalTrials.gov. AI-assisted translation, last sync: 7/1/2026.
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