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

ConditionsBreast Cancer With Brain MetastasisHER2-positive Breast Cancer
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexFemale
Age18-70
SponsorFudan University

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Female, aged 18-70 years old.

ECOG score ranges from 0 to 1.

Expected survival period is greater than 12 weeks.

Histologically confirmed invasive HER2 positive breast cancer (HER2 IHC+++or FISH/CISH positive, all samples need to be verified by the pathology department of the research center).

Disqualifiers

Transfer treatment exceeding 2 lines, or previous use of T-DXd or nalatinib.

Meningeal metastasis.

Brain metastases that require emergency intervention treatment, or brain metastases that require treatment with more than 3mg/d dexamethasone or equivalent drugs.

A history of clinically significant or uncontrolled heart disease, including congestive heart failure, angina, myocardial infarction within the past 6 months, or ventricular arrhythmia.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 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

Treatment groups

202 Participants
are divided into 2 treatment groups
Group A: T-DXdActive comparator 1 intervention
Group B: T-DXd+NeratinibExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Progression Free Survival(PFS)

Time to progressive disease (according to RECIST1.1)

Time frame
24 months

Secondary outcomes

1

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
24 months
2

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
24 months
3

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
24 months
4

Overall survival (OS)

Time from the enrollment to death of any cause

Time frame
48 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Fudan University

Lead sponsor

Source ClinicalTrials.gov
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