NCT07150208

T-DXd With or Without Bevacizumab for HER2-low Breast Cancer With Brain Metastasis

Trastuzumab Deruxtecan With or Without Bevacizumab for HER2-low Unresectable and/or Metastatic Breast Cancer With Brain Metastasis: A Multicenter, Randomized, Open Label, Phase II Trial (THUMB Trial)

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Sponsor: Fudan University · Academic / Other
• Sex: Female
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

A phase II, open-label, multicenter, randomized controlled trial exploring the efficacy and safety of Trastuzumab Deruxtecan combined with or without Bevicizumab in HER2-low breast cancer with brain metastasis.

Detailed description

This is a Phase II, open-label, multicenter, randomized controlled trial (THUMB study) comparing the efficacy and safety of trastuzumab deruxtecan (T-DXd) with or without bevacizumab for HER2-low expressing breast cancer with brain metastases. Patients receiving treatment in the metastatic setting must not have received more than 3 lines of therapy (HR-positive patients must have received a CDK4/6 inhibitor). Participants are randomized in a 1:1 ratio to receive treatment with T-DXd combined or not combined with bevacizumab.

Conditions

• Breast Cancer With Brain Metastasis
• HER2-low Expressing Breast Cancer

Interventions

Type	Name	Description
DRUG	Bevacizumab (Bev)	Bevacizumab is a drug that targets vascular endothelial growth factor (VEGF) and inhibits tumor angiogenesis, thereby inhibiting tumor growth and spread. In the treatment of breast cancer, Bevacizumab can be used in combination with chemotherapy to improve treatment outcomes and extend patients' progression-free survival and overall survival.
DRUG	Trastuzumab Deruxtecan (T-DXd)	Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) composed of an anti-HER2 monoclonal antibody (trastuzumab), a cleavable linker, and a topoisomerase I inhibitor (an exatecan derivative). It targets and binds to HER2-positive tumor cells, internalizes, and releases cytotoxic drugs to induce DNA damage and apoptosis. It also has a "bystander effect" that can kill neighboring tumor cells with low HER2 expression, enhancing anti-tumor activity. T-DXd has shown significant efficacy in HER2-positive advanced breast cancer, with key clinical trials (such as DESTINY-Breast03) confirming that its progression-free survival (PFS) and overall survival (OS) are superior to traditional second-line treatments, with a median PFS reaching 28.8 months. Additionally, for HER2-low-expressing (IHC 1+ or 2+/ISH-) metastatic breast cancer (in the DESTINY-Breast04 study), T-DXd can extend PFS and OS, becoming the first targeted therapy to alter the survival outcomes of such patients.

Timeline

• Start date: 2025-09-01
• Primary completion: 2027-09-01
• Completion: 2028-09-01
• First posted: 2025-09-02
• Last updated: 2025-09-02

Locations

1 site across 1 country: China