Clinical trial NCT06973525: This Study Aims to Optimize Neoadjuvant Therapy for HER2-positive Breast Cancer by Implementing a Dynamic Monitoring-guided Treatment Strategy.
Official 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）
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: HER2-positive Breast Cancer
Lead sponsor: Hebei Medical University Fourth Hospital
Sponsor class: OTHER
First posted: 2025-05-15
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Histologically confirmed invasive cancer of the breast and meet the clinical stage II（T2N0-1M0/T3N0M0）or III（T2N2M0/T3N1-2M0) criteria;
2. Age between18-70 years;
3. Eastern Cooperative Oncology Group (ECOG) performance status 0-1;
4. Histologically confirmed to be HER2-positive invasive breast cancer;
5. LVEF≥55%；
6. At least one measurable lesion according to RECIST version 1.1
7. 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);
8. 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:

1. Stage IV (metastatic) breast cancer.
2. The patient has a second primary malignant tumor, except for fully treated skin cancer.
3. 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.
4. 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.

Primary outcomes:
measure: tpCR
timeFrame: At the time of surgery
Secondary outcomes:
measure: EFS
timeFrame: 5 years
Other outcomes:
measure: bpCR
timeFrame: At the time of surgery
measure: ORR
timeFrame: During 24 weeks of the neoadjuvant treatment
measure: Incidence of Adverse Events
timeFrame: from consent to 28 days after last dose
Locations:
Study officials:
References: