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Safety and Efficacy of Trastuzumab Deruxtecan Versus CDK46 Inhibitor-based Endocrine Therapy as First-line Treatment for HR-positive and HER2-lowUltralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype
Led by MedSIR · Updated on 2026-06-02
200
Participants Needed
72
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating treatments for advanced breast cancer that is hormone receptor-positive HR-positive and HER2-low or ultralow, specifically in patients classified as non-luminal subtype by gene expression profiling PAM50. This phase II, international, multicenter, randomized trial aims to compare the effectiveness and safety of trastuzumab deruxtecan T-DXd versus a physicians choice of CDK46 inhibitor CDK46i combined with endocrine therapy ET as first-line treatments for these patients. Participants will be randomly assigned to receive either T-DXd at a dose of 5.4 mgkg administered intravenously on Day 1 of each 21-day cycle or a CDK46 inhibitor palbociclib, ribociclib, or abemaciclib chosen by their physician along with endocrine therapy fulvestrant, letrozole, anastrozole, or exemestane. Treatment continues until disease progression or unacceptable side effects. The study specifically includes patients with unresectable locally recurrent or metastatic breast cancer with non-luminal subtype confirmed by central PAM50 analysis. During the study, participants will undergo regular evaluations including imaging tests like CT or MRI to assess disease status and progression-free survival, which is the primary outcome measured for up to 25 months. Secondary outcomes include overall survival, response rates, duration of response, quality of life assessments, and monitoring of adverse events. Patients will be closely monitored for treatment effects and side effects, with follow-up planned to track health outcomes and treatment response throughout the study period.
CONDITIONS
Brief Title
Safety and Efficacy of T-DXd vs. CDK4/6i-based ET as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients must understand the study purpose and provide written consent.
- Female or male patients aged 18 years or older.
- ECOG performance status of 0 or 1.
- Life expectancy of at least 12 weeks.
- Confirmed HER2-low or HER2-ultralow breast cancer per recent guidelines.
- Non-luminal breast cancer subtype confirmed by central PAM50 analysis.
- HR-positive status with at least 1% positive receptor cells.
- Unresectable locally recurrent or metastatic breast cancer.
- Evaluable disease per RECIST v1.1; bone-only disease not allowed.
- Endocrine resistance or sensitivity criteria met.
- No prior systemic therapy for advanced disease.
- If treated with CDK4/6 inhibitor in adjuvant setting, treatment-free interval of 12 months or more.
- Adequate bone marrow, liver, and renal function.
- Resolution of prior therapy toxicities to Grade 1 or less.
- Women of childbearing potential must have negative pregnancy test and use effective contraception.
- Male participants must be sterile or use contraception.
- Accessible for treatment and follow-up.
You will not qualify if you...
- Participation in another therapeutic clinical trial currently.
- Recent treatment with cancer therapy or chloroquine/hydroxychloroquine.
- Prior treatment with trastuzumab deruxtecan or fulvestrant (with some exceptions).
- Advanced, symptomatic visceral disease risking life-threatening complications.
- Significant gastrointestinal disorders affecting drug absorption.
- Known active central nervous system involvement.
- Other active malignancies within 5 years (with some exceptions).
- Allergies to study drugs or their ingredients.
- Recent palliative radiotherapy or major surgery.
- Active or history of significant cardiac disease or abnormal heart rhythms.
- Severe pulmonary compromise or interstitial lung disease.
- Pregnant or lactating women or unwillingness to use contraception.
- Active infections including hepatitis B, hepatitis C, or HIV.
- Other uncontrolled infections or medical conditions interfering with study participation.
- Recent live or attenuated vaccination.
- History of uncontrolled seizures or serious psychiatric conditions.
- Use of medications known to strongly affect CYP3A4 enzyme.
- Known substance abuse or uncontrolled medical conditions contraindicating participation.
- Inability or unwillingness to follow study requirements.
Research Team
M
MEDSIR
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