This Study Aims to Optimize Neoadjuvant Therapy for HER2-positive Breast Cancer by Implementing a Dynamic Monitoring-guided Treatment Strategy.

NCT06973525 | Not Yet Recruiting Phase 2

• 1 other identifier: Pending Assignment
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to optimize neoadjuvant therapy for HER2-positive breast cancer by implementing a dynamic monitoring-guided treatment strategy. Patients will initially receive trastuzumab, pyrotinib, and albumin-bound paclitaxel. Those who do not achieve a radiological response after Cycle 2 will switch to SHR-A1811 (a HER2-targeted antibody-drug conjugate) combined with pertuzumab. The primary objective is to evaluate whether this sequential treatment strategy improves the pathological complete response (pCR) rate while maintaining safety. The study will also explore the value of dynamic efficacy monitoring in guiding treatment adjustments and assess the safety and tolerability of the regimens.

Conditions

HER2-positive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• tpCR

  Total pathological complete response (tpCR: ypT0-is/ypN0)

  At the time of surgery

Secondary Outcomes (1)

• EFS

  5 years

Other Outcomes (3)

• bpCR

  At the time of surgery

• ORR

  During 24 weeks of the neoadjuvant treatment

• Incidence of Adverse Events

  from consent to 28 days after last dose

Study Arms (2)

SHR-A1811+Pertuzumab

EXPERIMENTAL

Patients will initially receive trastuzumab, pyrotinib, and albumin-bound paclitaxel. Those who do not achieve a radiological response after Cycle 2 will switch to SHR-A1811 (a HER2-targeted antibody-drug conjugate) combined with pertuzumab.

Drug: Patients will initially receive trastuzumab, pyrotinib, and albumin-bound paclitaxel. Those who do not achieve a radiological response after Cycle 2 will switch to SHR-A1811 (a HER2-targeted antibody

trastuzumab, pyrotinib, and nab-paclitaxe

ACTIVE COMPARATOR

Patients will initially receive trastuzumab, pyrotinib, and nab-paclitaxel. Those who achieve a partial response (PR) or complete response (CR) after cycle 2 will continue on the same regimen.

Drug: Patients will initially receive trastuzumab, pyrotinib, and nab-paclitaxel. Those who achieve a partial response (PR) or complete response (CR) after cycle 2 will continue on the same regimen.

Interventions

Patients will initially receive trastuzumab, pyrotinib, and albumin-bound paclitaxel. Those who do not achieve a radiological response after Cycle 2 will switch to SHR-A1811 (a HER2-targeted antibody DRUG

Drug: SHR-A1811 Drug: Pertuzumab

SHR-A1811+Pertuzumab

Patients will initially receive trastuzumab, pyrotinib, and nab-paclitaxel. Those who achieve a partial response (PR) or complete response (CR) after cycle 2 will continue on the same regimen. DRUG

Patients will initially receive trastuzumab, pyrotinib, and nab-paclitaxel. Those who achieve a partial response (PR) or complete response (CR) after cycle 2 will continue on the same regimen.

trastuzumab, pyrotinib, and nab-paclitaxe

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed invasive cancer of the breast and meet the clinical stage II（T2N0-1M0/T3N0M0）or III（T2N2M0/T3N1-2M0) criteria;
• Age between18-70 years;
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
• Histologically confirmed to be HER2-positive invasive breast cancer;
• LVEF≥55%；
• At least one measurable lesion according to RECIST version 1.1
• Normal organ and marrow function: Hemoglobin (HB) ≥90 g/L (No blood was transfused within 14 days), Absolute neutrophil count ≥ 1500/μL, Platelets ≥ 75,000/μL, Total bilirubin ≤ 1.5 x ULN), aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT) ≤ 3 x ULN, creatinine \< 1 x ULN, endogenous creatinine clearance \> 50 ml/min (Cockcroft-Gault formula);
• Non-pregnant and non-lactating, fertile female subjects were required to use a medically approved contraceptive method for the duration of the study treatment and at least 3 months after the last use of the study drug; Ability to understand and willingness to sign a written informed consent

You may not qualify if:

• Stage IV (metastatic) breast cancer.
• 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; 5.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.
• Individuals with a known history of allergies to the drug components of this protocol; 7.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.

Sponsors & Collaborators

• Hebei Medical University Fourth Hospital: lead

MeSH Terms

Interventions

pyrotinib

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 15, 2025
• Study Start: September 1, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2032
• Last Updated: August 5, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share