RecruitingPhase 2NCT06486883

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

A Randomized Phase II Study to Evaluate the Safety and Efficacy of Trastuzumab Deruxtecan Versus CDK4/6 Inhibitor-based Endocrine Therapy as First-line Therapy of HR-positive and HER2-low/Ultralow Advanced Breast Cancer Patients Classified as Non-luminal Subtype According to Gene Expression Profiling.


Sponsor

MedSIR

Enrollment

200 participants

Start Date

Jun 30, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

This trial studies a type of advanced breast cancer defined as hormone receptor HR-positive/HER2-negative and classified as non-luminal by gene expression profiling (PAM50). Patients will be treated with trastuzumab deruxtecan (T-DXd) or with physician's choice of CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET). The main purpose of the study is to analyze the efficacy of T-DXd in patients who have HR-positive and HER2-low/ultralow advanced breast cancer classified as non-luminal subtype.


Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This trial is comparing two treatments in adults with hormone receptor-positive, HER2-low or HER2-ultralow advanced breast cancer that is classified as a non-luminal subtype (a more aggressive type): the antibody-drug conjugate T-DXd (trastuzumab deruxtecan) versus the standard hormonal therapy combined with a CDK4/6 inhibitor. **You may be eligible if...** - You are 18 or older - You have advanced (unresectable or metastatic) breast cancer that is hormone receptor-positive and has low or very low HER2 expression on tumor testing - Your tumor has been classified as non-luminal subtype by a central laboratory - You have a good performance status (ECOG 0-1) and a life expectancy of at least 12 weeks - You have not received chemotherapy for your advanced disease **You may NOT be eligible if...** - Your breast cancer has high HER2 expression (HER2-positive) - You are classified as the luminal subtype - You have active brain metastases or serious organ dysfunction - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

DRUGTrastuzumab deruxtecan (T-DXd, DS-8201a)

Patients will receive T-DXd 5.4 mg/kg body weight administered as an intravenous (IV) infusion on Day 1 (D1) of each 21-day cycle. The initial dose will be administered as a 90-minute IV infusion.

DRUGCDK4/6i plus ET

Patients will receive physician's choice of CDK4/6 inhibitor (CDK4/6i) including palbociclib, ribociclib, and abemaciclib; physician's choice of endocrine therapy (ET) including fulvestrant, letrozole, anastrozole, and exemestane.


Locations(56)

Algemeen Ziekenhuis Klina

Brasschaat, Belgium

CHU Helora - Hopital de Mons

Mons, Belgium

Cliniques universitaires Saint-Luc

Woluwe-Saint-Lambert, Belgium

CHU Lyon Sud

Lyon, France

Institut Curie

Paris, France

CHU Saint Etienne

Saint-Priest-en-Jarez, France

Klinikum Worms - Frauenklinik

Worms, Germany

A.O.U. Ospedali Riuniti di Ancona

Ancona, Italy

Centro di Riferimento Oncologico di Aviano

Aviano, Italy

AOU Careggi

Florence, Italy

Ospedale Policlinico San Martino

Genova, Italy

Ospedale di Macerata

Macerata, Italy

Instituto Europeo di Oncologia

Milan, Italy

Ospedale San Gerardo

Monza, Italy

Federico II Napoli

Naples, Italy

Istituto Nazionale Tumori Irccs "Fondazione G Pascale"

Naples, Italy

Azienda Ospedaliero- Universitaria Maggiore Della Carita

Novara, Italy

Oncologia medica AUSL Piacenza

Piacenza, Italy

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Medtrials Sp. z o.o.

Krakow, Poland

Unidade Local de Saúde de Trás-os-Montes e Alto Douro

Lordelo, Vila Real District, Portugal

Hospital de Cascais

Alcabideche, Portugal

Unidade Local de Saúde Amadora/Sintra - Hospital Fernando da Fonseca

Amadora, Portugal

Unidade Local de Saúde do Alto Ave

Braga, Portugal

Unidade Local de Saúde de Santa Maria

Lisbon, Portugal

Instituto Portugues Oncologia de Porto (IPO)

Porto, Portugal

Hospital Quirónsalud Sagrado Corazón

Barcelona, Barcelona, Spain

Hospital San Pedro de Alcántara

Cáceres, Cáceres, Spain

Institut Català d' Oncologia Girona (ICO)

Girona, Girona, Spain

Hospital Universitario Clínico San Cecilio

Granada, Granada, Spain

Complejo Hospitalario de Jaén

Jaén, Jaén, Spain

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, Spain

Hospital Clínico Universitario Virgen de la Arrixaca

Murcia, Murcia, Spain

Hospital Universitari Sant Joan de Reus

Reus, Tarragona, Spain

Hospital Clínico Universitario de Valencia

Valencia, Valencia, Spain

Complejo Hospitalario Universitario A Coruña (CHUAC)

A Coruña, Spain

Centro Oncológico de Galicia

A Coruña, Spain

Hospital Universitario San Juan de Alicante

Alicante, Spain

Institut Català d' Oncologia Badalona (ICO)

Badalona, Spain

UOMI Cancer Center

Barcelona, Spain

Hospital Universitari Dexeus

Barcelona, Spain

Hospital Clínic i Provincial de Barcelona

Barcelona, Spain

Hospital Universitario de Basurto

Bilbao, Spain

Hospital Universitario Arnau de Vilanova de Lleida

Lleida, Spain

Hospital Beata María Ana

Madrid, Spain

Hospital Clínico San Carlos

Madrid, Spain

Hospital Universitario Doce de Octubre

Madrid, Spain

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Complejo Hospitalario Universitario de Santiago (CHUS)

Santiago de Compostela, Spain

Hospital Universitario Virgen Macarena

Seville, Spain

Instituto Valenciano de Oncología (IVO)

Valencia, Spain

Hospital Universitari i Politècnic La Fe

Valencia, Spain

Hospital Arnau de Vilanova de Valencia

Valencia, Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, Spain

Hospital QuirónSalud Zaragoza

Zaragoza, Spain

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NCT06486883


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