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Trastuzumab Deruxtecan vs Endocrine Therapy in Low-HER2 HR+ Advanced Breast Cancer

NCT06837792 · Status: RECRUITING · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 141

Last updated 2025-04-29

No results posted yet for this study

Summary

"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

  • Hormone Receptor(HR)-Positive, Low HER2 Advanced Breast Cancer Patients (HER2 IHC 1+ or 2+ & ISH Negative)

Interventions

DRUG

Experimental treatment arm

Trastuzumab deruxtecan (T-DXd) 5.4mg/kg intravenous infusion every 3 weeks. (1 cycle = 3 weeks)

DRUG

Control treatment arm

1. Fulvestrant intramuscular injection of two 250mg injection every 4 weeks (every 2 weeks for the first cycle, 1 cycle = 4 weeks) 2. Fulvestrant (administered same as above) + alpelisib 300mg oral administration every day (1 cycle = 4 weeks)\* 3. Exemestane 25mg oral administration every day (1 cycle = 4 weeks) 4. Exemestane 25mg + everolimus 10mg oral administration every day (1 cycle = 4 weeks) 5. Tamoxifen 20mg oral administration every day (1 cycle = 4 weeks) 6. Fulvestrant (administered same as above) + Capivasertib 400mg oral administration twice a day(dosed on Days 1 to 4 in each week of a 28-day treatment cycle) * 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

Sponsors & Collaborators

  • Yonsei University

    lead OTHER

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
19 Years
Sex
FEMALE
Healthy Volunteers
No

Timeline & Regulatory

Start
2023-10-01
Primary Completion
2026-10-01
Completion
2026-10-01

Countries

  • South Korea

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06837792 on ClinicalTrials.gov