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Breast Cancer With Brain MetastasisPhase 2THUNDERNCT07152782

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

A Phase 2 study testing Neratinib and Trastuzumab Deruxtecan in people with Breast Cancer With Brain Metastasis and HER2-positive Breast Cancer, run by Fudan University at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

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 Read more about this study

Who is it for?
Ages 18 to 70 years, women only
What is being tested?
Neratinib and Trastuzumab Deruxtecan
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
202 participants
Where
1 siteChina
Study dates
24 Sep 2025to Nov 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • -
  • Participants must meet all of the following inclusion criteria in order to be enrolled in this study:
  • 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).
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  • Tumor staging: recurrent or metastatic breast cancer; Patients with local recurrence need to be confirmed by the researcher that radical surgical resection cannot be performed.
  • The subject has at least one lesion (measurable and/or unmeasurable) that has not received radiation therapy in the past.
  • MRI or CT shows brain metastasis and meets one of the following conditions:
  • Untreated brain parenchymal metastases detected through imaging screening;
  • Stable or progressive brain parenchymal metastases that have undergone previous local treatment and meet one of the following conditions:
  • Stable imaging for ≥ 4 weeks;
  • New brain parenchymal metastases detected by MR or CT.
  • Transfer treatment ≤ 2 lines, and did not receive T-DXd or nalatinib.
  • The main organ functions are basically normal, meeting the following conditions:
  • The standard for blood routine examination should meet: HB ≥ 90g/L (no blood transfusion within 14 days); ANC≥1.5×109/L；PLT≥75×109/L；
  • Biochemical tests must meet the following standards: TBIL ≤ 1.5 × ULN (upper limit of normal value); ALT and AST ≤ 3 × ULN; If there is liver metastasis, ALT and AST should be ≤ 5 × ULN; Serum Cr ≤ 1.5 × ULN, endogenous creatinine clearance rate ≥ 30mL/min (Cockcroft Gault formula).
  • Prior to enrollment, the use of mannitol and hormone therapy is allowed, but the medication dosage should be stable for at least one week without the need for an increase.
  • Female participants with fertility agreed to take effective contraceptive measures until 3 months after the last use of medication.
  • The subjects voluntarily joined this study, signed informed consent forms, had good compliance, and cooperated with follow-up.

Who cannot join

  • -
  • Subjects with any of the following conditions are not eligible for inclusion in this study:
  • 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.
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  • Due to ongoing grade ≥ 2 adverse reactions caused by previous treatments (excluding hair loss).
  • Pregnancy period.
  • Other malignant tumors within the past 5 years, excluding cured cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin.
  • Unable to swallow, chronic diarrhea, and intestinal obstruction, there are multiple factors that affect medication intake and absorption.
  • There is a third interstitial fluid accumulation that cannot be controlled by drainage or other methods (such as a large amount of pleural fluid and ascites).
  • Participated in clinical trials of other anti-tumor drugs within 4 weeks prior to the first use of the investigational drug.
  • Long term unhealed wounds or fractures with incomplete healing.
  • Known subjects with active HBV or HCV infection.
  • Active primary immunodeficiency, known to be HIV positive.
  • Uncontrolled infections requiring intravenous injection of antibiotics, antiviral drugs, or antifungal drugs.
  • A history of non communicable ILD/pneumonia requiring steroids, currently suffering from ILD/pneumonia, or unable to rule out suspected ILD/pneumonia through imaging during screening.
  • Lung standard:
  • Pulmonary specific comorbidities with clinically significant diseases, including but not limited to any potential pulmonary diseases (such as pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive pulmonary disease, pleural effusion, etc. within 3 months of recruitment).
  • Any autoimmune disease, connective tissue disease, or inflammatory disease (such as rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.). There are records or suspicions of lung involvement during screening. For participants participating in the study, all detailed information about the disease should be recorded in the CRF.
  • Previous complete lung resection surgery.
  • Individuals with allergies, or those with a known history of allergies to the components of this medication regimen, or subjects who are allergic to other monoclonal antibodies.
  • Researchers believe that substance abuse or medical conditions may interfere with participants' participation in clinical studies or the evaluation of clinical study results.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Zhimin Shao, Professor contact

08664175590 Ext. 88807

zhimingshao@yahoo.com

Guantian Lang, Doctor contact

08664175590 Ext. 65277

langguantian@126.com

China1 site, 1 recruiting

  • Fudan University Shanghai Cancer Center

    Shanghai

    Linxiaoxi Ma

    Recruiting

Other trials in China

About this study

Official title: Trastuzumab Deruxtecan With or Without Neratinib for HER2-positive Unresectable and/or Metastatic Breast Cancer With Brain Metastasis: A Multicenter, Randomized, Open Label, Phase II Trial (THUNDER 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

Read the detailed description

This study is a prospective, multicenter, open-label, Phase II, randomized controlled clinical trial aimed at evaluating the efficacy and safety of T-DXd with or without neratinib in patients with HER2-positive breast cancer with brain metastases. All eligible subjects will be randomly assigned in a 1:1 ratio across multiple centers in China to receive either T-DXd combined with neratinib or T-DXd monotherapy until extracranial progression as defined by RECIST 1.1, unless unacceptable toxicity occurs, consent is withdrawn, or other criteria for discontinuation are met.

Being tested
Neratinib, Trastuzumab Deruxtecan
Keywords
Breast Cancer with Brain Metastasis, HER2-positive Breast Cancer, Trastuzumab Deruxtecan, Neratinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NeratinibDrug

    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 DeruxtecanDrug

    Also called DS8201

    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 groups in NCT07152782
Study groupRoleWhat they receive
T-DXdActive comparatorT-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W).
Receives: Drug: Trastuzumab Deruxtecan
T-DXd+NeratinibExperimentalT-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W). Neratinib: 200mg po, D1-21, every 3 weeks (Q3W).
Receives: Drug: Neratinib; Drug: Trastuzumab Deruxtecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival(PFS)

    Time to progressive disease (according to RECIST1.1)

    Measured: 24 months

Secondary outcomes (5)

  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.

    Measured: 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

    Measured: 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.

    Measured: 24 months

  4. Overall survival (OS)

    Time from the enrollment to death of any cause

    Measured: 48 months

  5. Safety and Tolerability

    Safety and Tolerability Will be Assessed According to Standard (CTCAE Version 5.0) Toxicity Reporting Criteria.

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2025
  2. Study start24 Sep 2025
  3. Primary completionAug 2029 (estimated)
  4. Study completionNov 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
202 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07152782
Sponsor's protocol ID
SCHBCC- N0101
Acronym
THUNDER
Status last verified
Sep 2026
First submitted
26 Aug 2025
Last updated
28 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Neratinib and Trastuzumab Deruxtecan in people with Breast Cancer With Brain Metastasis and HER2-positive Breast Cancer, run by Fudan University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Zhimin Shao, Professor (08664175590 Ext. 88807, zhimingshao@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival(PFS) (time frame: 24 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07152782.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2026.

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