Testing Pyrotinib, Fulvestrant and Dalpiciclib After Trastuzumab Rezetecan in Advanced Breast Cancer

Trial details

Who runs it

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Trial code

NCT07892274

Record updated

23 October 2026

Original description

The purpose of this clinical trial is to evaluate whether, in patients with hormone receptor-positive (HR-positive) and HER2-positive advanced breast cancer whose disease has progressed after trastuzumab-based therapy, switching to pyrotinib, fulvestrant, and dalpiciclib after induction with trastuzumab rezetecan-among those without disease progression-is superior to continued treatment with trastuzumab rezetecan. The three medicines are pyrotinib (a medicine that blocks HER2 and similar signals), fulvestrant (a hormone therapy), and dalpiciclib (a medicine that slows cancer cell division).Read full original descriptionShow less

An Open-Label, Multicenter Clinical Study of Trastuzumab Rezetecan Followed by Pyrotinib in Combination With Fulvestrant and Dalpiciclib in Patients With HR-Positive, HER2-Positive Advanced Breast Cancer

The purpose of this clinical trial is to evaluate whether, in patients with hormone receptor-positive (HR-positive) and HER2-positive advanced breast cancer whose disease has progressed after trastuzumab-based therapy, switching to pyrotinib, fulvestrant, and dalpiciclib after induction with trastuzumab rezetecan-among those without disease progression-is superior to continued treatment with trastuzumab rezetecan. The three medicines are pyrotinib (a medicine that blocks HER2 and similar signals), fulvestrant (a hormone therapy), and dalpiciclib (a medicine that slows cancer cell division).

The primary question this study aims to answer is:

Does switching to pyrotinib, fulvestrant, and dalpiciclib prolong the time participants live without their cancer worsening compared with continued treatment with trastuzumab rezetecan?

The study will also assess overall survival, tumor response to treatment, and adverse events.

Researchers will compare the three-medicine combination with continued trastuzumab rezetecan.

Participants will:

Receive trastuzumab rezetecan once every 3 weeks for 6 cycles.

If the cancer has not worsened after these 6 cycles, be randomly assigned to receive either the three-medicine combination or continued trastuzumab rezetecan.

Undergo imaging scans every 6 weeks during the first 24 weeks and every 9 weeks thereafter to assess the cancer.

Undergo blood tests, cardiac assessments, and other safety evaluations during treatment and follow-up.

Inclusion: Adult female patients aged 18 to 80 years with metastatic breast cancer confirmed by pathology or imaging, not amenable to curative surgery or radiotherapy; Pathologically confirmed estrogen receptor (ER) and/or progesterone receptor (PR) positive (≥10% tumor cells by immunohistochemistry) and HER2-positive (IHC 3+ or FISH-positive); Disease progression during or within 1 year after neoadjuvant/adjuvant trastuzumab, or prior trastuzumab-based therapy for metastatic disease; Eastern Cooperative Oncology Group (ECOG) performance status 0-2 and estimated life expectancy ≥3 months; Prior treatment-related toxicity resolved to Grade ≤1 per NCI CTCAE v4.03 (except alopecia or other toxicity deemed by the investigator not to pose a safety risk); Adequate bone marrow function within 1 week before enrollment: white blood cell count ≥3.0×10⁹/L, absolute neutrophil count ≥1.5×10⁹/L, platelet count ≥100×10⁹/L; Adequate hepatic, renal, and cardiac function within 1 week before enrollment: total bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN (≤5×ULN in patients with liver metastases); serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min; left ventricular ejection fraction ≥55%; QTcF ≤470 ms; Patient understands the study procedures, voluntarily agrees to participate, and provides written informed consent.

Exclusion: No prior trastuzumab, chemotherapy, or endocrine therapy; Considered by the investigator to be a candidate for chemotherapy; Inability to swallow, chronic diarrhea, or bowel obstruction that may affect drug administration or absorption; More than one prior line of endocrine therapy, chemotherapy, or targeted therapy for metastatic disease; Concurrent other anticancer therapy; Any severe concomitant disease that, in the investigator's judgment, would compromise patient safety or study completion; Other malignancy within the past 5 years, except curatively treated cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma of the skin; Known allergy to any component of the study drugs; history of immunodeficiency, including HIV positivity, HCV, active hepatitis B, or other acquired/congenital immunodeficiency; history of organ transplantation; History of neurological or psychiatric disorders, including epilepsy or dementia; Any other condition that, in the investigator's judgment, makes the patient unsuitable for the study; Severe cardiac disease or condition, including but not limited to: heart failure or systolic dysfunction (LVEF ≤50%), uncontrolled hypertension, significant ventricular arrhythmia, high-grade atrioventricular block, angina requiring anti-anginal therapy, clinically significant valvular disease, or ECG evidence of acute myocardial infarction; Central nervous system metastases; Visceral crisis; Pregnancy or lactation, or a positive pregnancy test at baseline in women of childbearing potential.

ClinicalTrials.gov NCT07892274