NCT06750484

Trial of Trastuzumab Deruxtecan in Previously Treated HER2

Open-label Single-arm Phase 2 Trial of Trastuzumab Deruxtecan in Previously Treated HER2-Immunohistochemistry (IHC) 0 Advanced Breast Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Yale University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to test the good and bad effects of a drug called trastuzumab deruxtecan (T-DXd) in adult patients with metastatic HER2-negative breast cancer and which patients might benefit the most from T-DXd.

Detailed description

HER2 (human epidermal growth factor receptor 2) is a gene that can play a role in the development of breast cancer. Genes like HER2 and the proteins they make influence how a breast cancer behaves and how it might respond to a specific treatment. A score of 0 on the HER2 immunohistochemistry (IHC) test indicates that breast tissue is HER2-negative. Drugs that fight cancer by targeting the growth of HER2 genes, such as the monoclonal antibody trastuzumab, have not traditionally been used in patients with HER2-negative tumors because trastuzumab works by attaching to HER2 and stopping cancer cells from growing and dividing. However, about half of breast cancers that are categorized as HER2-negative like yours, actually have low expression of HER2. and recent research has shown that newer generations of antibody-drug conjugates like trastuzumab show considerable survival benefit even in tumors that are not classified as HER2-positive. An antibody-drug conjugates is a combination of a monoclonal antibody like trastuzumab with an anticancer agent like deruxtecan. This combination that interrupts DNA replication in cancer cells. Antibody-drug conjugates like (T-DXd) are designed to target and kill cancer cells while sparing healthy cells. Prior research that has shown that the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) has outstanding activity and survival benefit in HER2-low breast cancers. The purpose of this study is to help us learn more about which patients might benefit most from T-DXd through a single-arm, open-label, phase 2 study to assess the safety and efficacy of T-DXd in HER2-negative subjects with unresectable and/or metastatic breast cancer. The researchers will measure the response to the T-DXd (the percentage of patients with complete response, partial response, stable disease, and progressive disease). Researchers will also look for biomarkers to determine the most accurate way to predict which patients without HER2-positive breast cancer will benefit the most from T-DXd. T-DXd has been FDA approved to treat adults with unresectable or metastatic HER2-low breast cancer who have received a prior chemotherapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy. Each treatment cycle is 21 days.

Conditions

• Breast Cancer Metastatic

Interventions

Type	Name	Description
DRUG	Trastuzumab Deruxtecan	Participants will receive the study drug trastuzumab deruxtecan (T-DXd) by IV infusion every 21 days. The number of treatment cycles will depend on how participants respond to treatment.

Timeline

• Start date: 2025-06-20
• Primary completion: 2028-12-31
• Completion: 2028-12-31
• First posted: 2024-12-27
• Last updated: 2026-02-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study