Trastuzumab rezetecan with or without radiotherapy for HER2‑positive advanced breast cancer that has spread to the brain.

An Open-label, Randomized, Controlled Trial of Trastuzumab Rezetecan Combined With Radiotherapy Versus Trastuzumab Rezetecan in the Treatment of HER2-positive Advanced Breast Cancer With Brain Metastases

This trial will test whether adding radiotherapy to trastuzumab rezetecan helps adults with HER2‑positive advanced breast cancer and untreated brain metastases control their brain tumors better than the drug alone.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 224 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Henan Cancer Hospital (other gov)
• Drugs / interventions: trastuzumab, radiation
• Locations: 1 site (Zhengzhou, Henan)
• Trial ID: NCT07100600 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 trial plans to enroll 224 adults with HER2‑positive advanced breast cancer and at least one measurable, untreated intracranial lesion and will assign them 1:1 to receive trastuzumab rezetecan with radiotherapy (FSRT or WBRT) or trastuzumab rezetecan alone. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. Key eligibility includes no prior cranial radiation, adequate organ function, life expectancy of at least six months, and no leptomeningeal disease. The study will compare intracranial tumor control and safety between the two groups.

Who should consider this trial

Good fit: Adult women (≥18 years) with pathologically confirmed HER2‑positive advanced breast cancer, at least one measurable untreated brain metastasis, no prior cranial radiation, adequate organ function, and life expectancy ≥6 months are ideal candidates.

Not a fit: Patients with leptomeningeal metastasis, prior treatment with certain exatecan‑based ADCs, urgent CNS complications needing surgery, uncontrolled heart or significant lung disease, or who have already had cranial radiation are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, combining radiotherapy with trastuzumab rezetecan could improve control of brain metastases and delay neurologic symptoms or disease progression.

How similar studies have performed: Antibody‑drug conjugates such as trastuzumab deruxtecan have shown intracranial activity in HER2‑positive breast cancer, but combining these ADCs with radiotherapy is not well studied and may carry higher toxicity risk.

Eligibility criteria

Inclusion Criteria:

1. Females ≥18 yrs old;
2. Pathologically confirmed HER2-positive advanced breast cancer;
3. At least one measurable intracranial lesion according to RANO-BM criteria, which had not received local treatment;
4. Without prior cranial radiation and had no indication for immediate local treatment or refuse to local treatment;
5. Life expectancy is not less than 6 months.
6. Adequate function of major organs.

Exclusion Criteria:

1. Subjects with leptomeningeal metastasis
2. CNS complications requiring emergency neurosurgical intervention
3. Previous treatment with trastuzumab deruxtecan (DS-8201a) or any other antibody drug conjugate (ADC) which consists of an exatecan derivative that is a topoisomerase 1 inhibitor;
4. Suffering from heart disease that is not well controlled or having clinical symptoms
5. History of clinically significant lung disease；
6. Other malignant tumors, excluding cured cervical carcinoma in situ, skin basal cell carcinoma or skin squamous cell carcinoma, have been diagnosed in the past five years.
7. Female subjects during pregnancy and lactation
8. Any other conditions that researchers believe that patients are unsuitable for this study.

Where this trial is running

Zhengzhou, Henan

• Professor — Zhengzhou, Henan, China (RECRUITING)

Conditions: HER2-positive Advanced Breast Cancer, Brain Metastases, Radiotherapy