NCT06486883

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.

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Sponsor: MedSIR · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

This is an international, multicenter, two-arm, randomized, phase II clinical trial for patients with unresectable locally recurrent or metastatic HR-positive and HER2-low/ultralow breast cancer classified as non-luminal by gene expression profiling. Female or male patients ≥ 18 years of age with HR-positive and HER2-low/ultralow locally recurrent inoperable or metastatic breast cancer classified as non-luminal subtype by central PAM50 analysis will be enrolled. Patients will be randomized to T-DXd 5.4 mg/kg body weight administered as an IV infusion on Day 1 of each 21-day cycle or physician's choice of CDK4/6 inhibitor plus endocrine therapy. The main objective of the study is to demonstrate that first-line T-DXd compared with CDK4/6i plus ET is superior in prolonging the progression free survival (PFS) based on investigator assessment in patients with HR-positive, HER2-low advanced breast cancer classified as non-luminal by central PAM50 analysis (HER2-low population) and all patients.

Conditions

• Advanced Breast Cancer
• Advanced Breast Carcinoma
• Hormone Receptor Positive Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Trastuzumab 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.
DRUG	CDK4/6i 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.

Timeline

• Start date: 2025-06-30
• Primary completion: 2027-01-01
• Completion: 2028-01-01
• First posted: 2024-07-05
• Last updated: 2026-04-02

Locations

56 sites across 7 countries: Belgium, France, Germany, Italy, Poland, Portugal, Spain