NCT06048718

T-DXd Therapy for HER2-low Breast Cancer Patients With Brain Metastases

Phase II Study of Trastuzumab-Deruxtecan (T-DXd; DS-8201a) in HER2-Low Breast Cancer Patients Presenting With Newly Diagnosed or Progressing Brain Metastases

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (actual)
• Sponsor: MedSIR · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

TUXEDO-4 is an international, multicentric, single arm, phase II study aiming to gather additional solid evidence of Trastuzumab-Deruxtecan (T-DXd) activity in patients with Human Epidermal Growth Factor Receptor 2 (HER2)-low breast cancer with active brain metastases. This study will analyze the efficacy of T-DXd as determined by overall response rate (ORR) at any timepoint as judged by best CNS response according to RANO-BM criteria.

Detailed description

This is an international, multicentric, single arm, phase II study to evaluate the safety and efficacy of T-DXd in HER2-low breast cancer with newly diagnosed or progressing brain metastases with or without untreated type II leptomeningeal disease (LMD). Upon meeting all selection criteria, a total of 27 patients will be enrolled as follows: 13 patients will be accrued in stage 1 to receive T-DXd and additional 14 patients will be accrued in stage 2 according to the number of responses seen in stage 1. The main objective is to analyze the efficacy of T-DXd as determined by ORR at any timepoint as judged by best CNS response according to RANO-BM criteria. End of study is estimated to occur approximately 11 months after the last patient included in the study starts treatment, unless premature termination of the study.

Conditions

• Breast Cancer
• Metastatic Breast Cancer

Interventions

Type	Name	Description
DRUG	Trastuzumab-Deruxtecan (T-DXd)	Trastuzumab-deruxtecan is a human HER2-directed antibody-drug conjugate (ADC) composed of humanized anti-HER2 immunoglobulin G1 (IgG1) monoclonal antibody (mAb) with the same amino acid sequence as trastuzumab, covalently linked to the membrane-permeable topoisomerase I inhibitor payload, DXd, an exatecan derivative, via a stable tetrapeptide-based linker, selectively cleaved within tumor cells.

Timeline

• Start date: 2024-06-05
• Primary completion: 2026-11-01
• Completion: 2026-11-01
• First posted: 2023-09-21
• Last updated: 2026-03-10

Locations

13 sites across 2 countries: Austria, Spain