SHR-A1811 and pertuzumab before surgery for HER2-positive breast cancer

SHR-A1811 Plus Pertuzumab in Combination With or Without Albumin-paclitaxel as Neoadjuvant Treatment for Early or Locally Advanced HER2-positive Breast Cancer：A Prospective, Randomized, Open-label, Phase II Trial.

This study tests whether adding SHR-A1811 to pertuzumab, with or without albumin-paclitaxel, helps people with early HER2-positive breast cancer reach a pathologic complete response before surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Henan Cancer Hospital (Government)
• Drugs / interventions: chemotherapy, pertuzumab, trastuzumab
• Locations: 1 site (Zhengzhou, Henan)
• Trial ID: NCT06927180 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 trial enrolls adults with early or locally advanced HER2-positive invasive breast cancer and assigns them 1:1:1 to one of three 6-cycle neoadjuvant regimens: SHR-A1811 plus pertuzumab, SHR-A1811 plus pertuzumab and albumin-paclitaxel, or a standard TCbHP regimen (docetaxel, carboplatin, trastuzumab, pertuzumab). The primary endpoint is pathologic complete response (pCR) after neoadjuvant therapy, with safety and tolerability monitored as key secondary outcomes. Eligible participants must have measurable primary lesions, adequate organ and bone marrow function, and preserved cardiac function. The trial is conducted at Henan Cancer Hospital and directly compares the new SHR-A1811-containing combinations against the current standard regimen.

Who should consider this trial

Good fit: Adults aged 18–70 with histologically confirmed HER2-positive early or locally advanced (clinical T2–T4, M0) invasive breast cancer, measurable disease, ECOG 0–1, and adequate organ and cardiac function are ideal candidates.

Not a fit: Patients with metastatic (M1) disease, HER2-negative tumors, significant cardiac dysfunction, inadequate organ or marrow function, prior systemic therapy for the current cancer, or inability to tolerate protocol treatments are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, these combinations could increase pCR rates and potentially improve long-term outcomes for people with early HER2-positive breast cancer.

How similar studies have performed: Prior neoadjuvant trials combining established HER2-targeted antibodies (for example trastuzumab plus pertuzumab) have improved pCR rates, but SHR-A1811 is a newer agent with limited published clinical data to date.

Eligibility criteria

Inclusion Criteria:

* Age: 18-70 years old, ECOG 0-1 point.
* Clinical T2-T4, with any LN, M0.
* HER2+, invasive breast cancer confirmed by histopathology;(HER2 positive expression means that there is at least one case of tumor cell immunohistochemical staining intensity of 3+or positive confirmed by fluorescence in situ hybridization \[FISH\] in the pathological test/review of the primary focus conducted by the Pathology Department of the Research Center Hospital).
* Having clinically measurable lesions: measurable lesions displayed on ultrasound, mammography, or MR (optional) within the first month of randomization.
* Organ and bone marrow function tests within one month before chemotherapy indicate no contraindications to chemotherapy：Absolute value of neutrophil count ≥ 1.5 × 10\^9/L; Hemoglobin ≥ 90g/L; Platelet count ≥ 100 × 10\^9/L; Total bilirubin≤1.5 ULN (upper limit of normal value); Creatinine≤1.5 × ULN; AST/ALT ≤ 2.5 × ULN.
* Cardiac ultrasound: Left ventricular ejection fraction (LVEF ≥ 50%).
* Women of childbearing age tested negative for serum pregnancy test 7 days before randomization.
* Sign an informed consent form.

Exclusion Criteria:

* Stage IV (metastatic) breast cancer.
* Has received chemotherapy, endocrine therapy, targeted therapy, reflex therapy, etc. for this disease.
* The patient has a second primary malignant tumor, except for fully treated skin cancer.
* The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures.
* The presence of uncontrolled cardiovascular and cerebrovascular disease, including (but not limited to) any of the following within the 6 months prior to the first dose: congestive heart failure (NYHA III or IV), myocardial infarction or cerebral infarction, pulmonary embolism, unstable angina, or arrhythmia requiring treatment at the time of screening; Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restricted cardiomyopathy, undefined cardiomyopathy); A clinically significant history of prolonged QTc, grade II type II atrioventricular block or grade III atrioventricular block or QTc interphase (F method) \> 470 msec (female); Atrial fibrillation (EHRA grade ≥2b); Unmanageable hypertension, which the investigators judged unsuitable for study participation.
* Due to serious and uncontrollable other medical diseases, researchers believe that there are contraindications to chemotherapy.
* Individuals with a known history of allergies to the drug components of this protocol;
* Having a history of immunodeficiency, including HIV testing positive, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.

Where this trial is running

Zhengzhou, Henan

• Henan Cancer Hospital — Zhengzhou, Henan, China (Recruiting)

Study contacts

• Principal investigator: Zhenzhen Liu — Henan Cancer Hospital
• Study coordinator: Zhenzhen Liu

Conditions Breast Cancer Early Stage Breast Cancer; Breast Cancer; HER2-positive Breast Cancer; pathologic complete response; SHR-A1811; Pertuzumab; Albumin-Paclitaxel