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

NCT07152782 | Not Yet Recruiting Phase 2

• 1 other identifier: SCHBCC- N0101
• Study Type: interventional
• Target: 202
• Locations: 0 countries
• Sites: N/A

Brief 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

Conditions

Breast Cancer With Brain Metastasis; HER2-positive Breast Cancer

Keywords

Breast Cancer with Brain Metastasis; HER2-positive Breast Cancer; Trastuzumab Deruxtecan; Neratinib

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival(PFS)

  Time to progressive disease (according to RECIST1.1)

  24 months

Secondary Outcomes (5)

• CNS Progression-free survival (CNS-PFS)

  24 months

• Objective response rate (ORR)

  24 months

• CNS Objective response rate (CNS-ORR)

  24 months

• Overall survival (OS)

  48 months

• Safety and Tolerability

  24 months

Study Arms (2)

T-DXd

ACTIVE COMPARATOR

T-DXd: 5.4mg/kg intravenously (IV) every 3 weeks (Q3W).

Drug: Trastuzumab Deruxtecan

T-DXd+Neratinib

EXPERIMENTAL

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

Drug: Neratinib; Drug: Trastuzumab Deruxtecan

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.

T-DXd+Neratinib

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

Also known as: DS8201

T-DXd; T-DXd+Neratinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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:
• i) Untreated brain parenchymal metastases detected through imaging screening;
• Ii) 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Interventions

neratinib; trastuzumab deruxtecan

Central Study Contacts

Zhimin Shao, Professor

CONTACT

08664175590 Ext. 88807; zhimingshao@yahoo.com

Guantian Lang, Doctor

CONTACT

08664175590 Ext. 65277; langguantian@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 26, 2025
• First Posted: September 3, 2025
• Study Start: November 1, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2029
• Last Updated: September 3, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share