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NCT Number: NCT06973525

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

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.

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Key information

Age range

18 year–70 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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.

6.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.

Treatment and study plan

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

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.

Primary outcomes

  1. tpCR

    Time frame: At the time of surgery

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

Secondary outcomes

  1. EFS

    Time frame: 5 years

    Event-free survival

Other outcomes

  1. bpCR

    Time frame: At the time of surgery

    Breast pathological complete response (bpCR:ypT0-is)

  2. ORR

    Time frame: During 24 weeks of the neoadjuvant treatment

    Objective Response Rate (ORR) according to Response Evaluation Criteria in Solid

  3. Incidence of Adverse Events

    Time frame: from consent to 28 days after last dose

    Incidence of Adverse Events

Sponsors and collaborators

Lead sponsor

Hebei Medical University Fourth Hospital

Other

Registry information

Official study title

Optimizing Neoadjuvant Therapy for HER2-Positive Breast Cancer Based on Dynamic Efficacy Monitoring: A Trial of Trastuzumab Plus Pyrotinib and Albumin-Bound Paclitaxel Followed by SHR-A1811 Plus Pertuzumab(OnThePath Trial)

Acronym: HER2-DM-NACT

Important dates

Study start
2025
Primary completion
2027
Study completion
2032
First posted
May 15, 2025
Registry last updated
Aug 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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