T-DXd With or Without Neratinib for HER2 Positive Breast Cancer With Brain Metastasis

Sponsor
Fudan University
Study ID
NCT07152782
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

Eligibility Criteria

Sex
FEMALE
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Neratinib — DRUG
    Neratinib, as an irreversible pan-HER tyrosine kinase inhibitor (TKI), holds a unique position in the treatment of HER2-positive breast cancer. From a molecular perspective, Neratinib irreversibly binds to the intracellular kinase domains of HER1 (EGFR), HER2, and HER4 through covalent bonds, comprehensively blocking signal transduction of the HER family. This mechanism of action is markedly different from reversible TKIs such as lapatinib. Neratinib's irreversible binding characteristic allows for a more sustained inhibition of target activity, maintaining anti-tumor effects even after drug plasma concentrations have decreased. This feature is particularly important for HER2-positive breast cancer, which requires continuous suppression of proliferative signals.
  • Trastuzumab Deruxtecan — DRUG
    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

Study Details

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

Key Dates

Start date
Nov 30, 2025
Status verified
Aug 2025
Primary completion
Nov 30, 2027
Completion
Nov 30, 2029

Study Design

Enrollment
202 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: T-DXd
    T-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W).
  • Experimental: T-DXd+Neratinib
    T-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W). Neratinib: 200mg po, D1-21, every 3 weeks (Q3W).

Primary Outcome Measure

Progression Free Survival(PFS) [ Time Frame: 24 months ]

Central Contacts

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