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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
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.
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.
Fudan University Shanghai Cancer Center
Shanghai, China
Progression Free Survival(PFS)
Time to progressive disease (according to RECIST1.1)
Time frame: 12 months
CNS Progression-free survival (CNS-PFS)
Time from enrollment to the first radiographic documented disease progression (PD) of all CNS target lesions (RANO-BM criteria) or death from any cause without progression was recorded.
Time frame: 12 months
Objective response rate (ORR)
Partial response is defined as a decrease by 30% or more in sums of longest diameter of measurable target lesions
Time frame: 12 months
CNS Objective response rate (CNS-ORR)
The proportion of patients with complete response (CR) and partial response (PR) evaluated as the best response observed from enrollment to progression of all CNS target lesions assessed according to RANO-BM criteria among the total number of patients who could be evaluated.
Time frame: 12 months
Overall survival (OS)
Time from the enrollment to death of any cause
Time frame: 12 months
Safety and Tolerability
Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 5.0) Toxicity Reporting Criteria.
Time frame: 12 months
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