T-DXd with brain radiotherapy for HER2-positive and HER2-low breast cancer brain metastases

Exploration of the Safety and Efficacy of T-DXd Concurrent With Brain Radiotherapy in Patients With Brain Metastases HER2-positive/HER2-low Advanced Breast Cancer

This trial tests whether giving T‑DXd (trastuzumab deruxtecan) at the same time as local brain radiotherapy is safe and helps people with HER2‑positive or HER2‑low breast cancer that has spread to the brain.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences (Academic / other)
• Drugs / interventions: trastuzumab, chemotherapy, immunotherapy
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07117864 on ClinicalTrials.gov

What this trial studies

This is an interventional, single‑center trial testing concurrent administration of T‑DXd with local brain radiotherapy in adult women with histologically confirmed HER2‑positive or HER2‑low breast cancer and radiologically confirmed brain metastases. Eligible patients are aged 18–75 with ECOG performance status 0–2 and adequate organ and cardiac function, and prior systemic therapies are allowed. Participants will receive T‑DXd alongside focal or whole‑brain radiotherapy according to local practice, with regular clinical, laboratory, and imaging follow‑up to monitor safety and intracranial response. Primary outcomes focus on safety and intracranial efficacy measures, with planned imaging and cardiac monitoring during and after treatment.

Who should consider this trial

Good fit: Ideal candidates are women aged 18–75 with HER2‑positive or HER2‑low invasive breast cancer, confirmed brain metastases, ECOG 0–2, and adequate blood, liver, kidney, and cardiac function.

Not a fit: Patients with poor performance status (ECOG >2), inadequate organ or cardiac function, non‑HER2 tumors, or those unable to travel to the treatment center are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, the combination could improve control of brain metastases and potentially extend time without progression while maintaining acceptable toxicity.

How similar studies have performed: Systemic T‑DXd has shown strong activity in HER2‑positive disease and some intracranial responses have been reported, but the concurrent use of T‑DXd with brain radiotherapy is relatively novel and not well established.

Eligibility criteria

Inclusion Criteria:

1. Female patients aged ≥18 and ≤75 years with histologically confirmed breast cancer.
2. ECOG performance status of 0 to 2.
3. HER2-positive or HER2-low invasive breast cancer, defined as:

   HER2-positive: IHC 3+ or IHC 2+ with FISH amplification; HER2-low: IHC 2+ without FISH amplification, or IHC 1+.
4. Confirmed diagnosis of breast cancer brain metastases.
5. Patients may have received prior chemotherapy (from first-line to multiple lines), HER2-targeted therapy (monoclonal antibodies), endocrine therapy, and immunotherapy.
6. Adequate organ function as defined below:

   Hematology:

   Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 80 × 10⁹/L (no blood transfusion within 14 days prior to first dose); Hemoglobin (Hb) ≥ 80 g/L;

   Serum biochemistry:

   Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 2.5 × ULN; Blood urea nitrogen (BUN) and serum creatinine ≤ 1.5 × ULN;

   Cardiac function:

   Echocardiography: Left ventricular ejection fraction (LVEF) ≥ 45%.
7. Subjects must voluntarily participate in the study and provide signed informed consent.

Exclusion Criteria:

1. Tumor-Related Symptoms and Treatments

   1. Uncontrolled moderate to large pleural effusion, ascites, or pericardial effusion requiring repeated drainage;
   2. Imaging (CT or MRI) showing tumor invasion of major blood vessels, or cases deemed by the investigator as highly likely to cause fatal hemorrhage due to vascular invasion during the study period;
   3. Signs of meningeal irritation such as neck stiffness, seizures, or cognitive impairment, or confirmed leptomeningeal metastasis by imaging (CT or MRI) or lumbar puncture;
   4. Uncontrolled or symptomatic hypercalcemia (defined as ionized calcium \> 1.5 mmol/L, serum calcium \> 12 mg/dL, or albumin-corrected serum calcium \> ULN), or symptomatic hypercalcemia requiring continued bisphosphonate treatment;
   5. Prior cranial radiotherapy;
   6. Prior treatment with trastuzumab deruxtecan (T-DXd).
2. Comorbidities / Medical History

   1. History of other malignancies for which the patient received any systemic anti-cancer therapy or local treatment (including surgery or radiotherapy), except for adequately treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin;
   2. Major surgery unrelated to breast cancer within 4 weeks prior to enrollment, or incomplete recovery from such surgery (diagnostic biopsies and PICC line placement are permitted);
   3. Known or suspected autoimmune diseases, except for the following conditions:

      Hypothyroidism due to autoimmune thyroiditis managed with hormone replacement therapy; Stable Type I diabetes mellitus with controlled blood glucose;
   4. Presence of interstitial lung disease (ILD), non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes, pulmonary fibrosis, acute pneumonia);
   5. HIV infection or known AIDS; active hepatitis (HBV defined as HBV-DNA ≥ 500 IU/mL; HCV defined as HCV-RNA above the lower limit of detection); concurrent HBV and HCV infection; autoimmune hepatitis;
   6. Severe infections within 4 weeks before first dose (e.g., bacteremia or severe pneumonia requiring hospitalization), or active infections requiring systemic antibiotic therapy of CTCAE grade ≥2 within 2 weeks before first dose, or unexplained fever \>38.5°C during screening or prior to first dose (fever deemed tumor-related may be eligible at the investigator's discretion); evidence of active tuberculosis within 1 year prior to first dose;
   7. Previous or planned allogeneic bone marrow transplantation or solid organ transplantation;

   Severe or uncontrolled cardiovascular disease, including but not limited to:

   History of heart failure or systolic dysfunction (LVEF \< 45%); High-risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate \> 100 bpm, significant ventricular arrhythmias (e.g., ventricular tachycardia), or high-grade atrioventricular (AV) block (e.g., Mobitz type II second-degree or third-degree AV block); Angina requiring anti-anginal medications; Clinically significant valvular heart disease; Transmural myocardial infarction on ECG; Poorly controlled hypertension (systolic BP \>180 mmHg and/or diastolic BP \>100 mmHg);
3. Known hypersensitivity to the investigational drug or any of its excipients, or a history of severe hypersensitivity reactions to other monoclonal antibodies.
4. Pregnant or breastfeeding women, women of childbearing potential with a positive baseline pregnancy test, or women of childbearing potential unwilling to use effective contraception during the study.
5. History of confirmed neurological or psychiatric disorders, including epilepsy or dementia; known history of psychiatric medication abuse, alcoholism, or substance abuse.
6. Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study.

Where this trial is running

Beijing, Beijing Municipality

• Cancer Hospital Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Qiao Li, MD

Conditions Breast Cancer