Overview

Purpose of the Study:

Primary Study Objective:

To evaluate the efficacy of pyrrolitinib maleate tablets in the treatment of HER-2-positive early or locally advanced breast cancer after adjuvant therapy with trastuzumab

Secondary Research Objectives:

To evaluate the safety of pyrrolitinib maleate tablets in the treatment of HER-2 positive early or locally advanced breast cancer after trastuzumab adjuvant therapy

Study Endpoints Primary Study Endpoint:

Invasive disease free survival (iDFS)

Secondary Study Endpoints:

1. overall survival (OS);
2. disease-free survival (DFS);
3. distant metastasis free survival (DDFS);
4. safety Study Population: Patients with early or locally advanced HER-2 positive breast cancer with clinical stage 0-III who have received prior neoadjuvant or adjuvant therapy. where the neoadjuvant and/or adjuvant treatment phase has been completed at least ≥24 weeks (8 dosing cycles) of trastuzumab therapy and the time interval between the end of the last course of trastuzumab therapy and entry into the study must be ≤1 year Study Design: Single-arm, multicenter, interventional study Administration Pyrrolitinib: The recommended dose of this product is 400 mg orally once daily within 30 minutes after breakfast for 52 weeks (approximately one year).

Dose adjustments may be made in accordance with this protocol, taking into account adverse reactions in subjects. Each consecutive suspension of piretinib during the course of the study should not exceed 14 days, prophylactic use of medications for the treatment of diarrhea is permitted during the course of treatment, multiple suspensions of study medication due to adverse events are permitted, and doses of piretinib that are missed for any reason will not be made up.

Eligibility

Inclusion Criteria:

• Age: 18-75 years;
• Invasive breast cancer with clinical stage 0-III and treated surgically;
• Histopathologically confirmed HER-2 positivity: immunohistochemistry (IHC) result of 3+ or in situ hybridization (ISH) result of HER-2 gene amplification (HER-2/CEP17 ≥ 2.0 or average HER-2 copy number/cell ≥ 6);
• Have undergone radical mastectomy or breast-conserving surgery for breast cancer, with no cancer left in the body and no recurrence of metastatic disease after

  surgery

  1. Pathologic test confirms that there is no residual invasive cancer at the margins and no residual ductal carcinoma in situ;
  2. Patients who have not received neoadjuvant therapy should have negative surgical margins, and there is no requirement for the presence of lymph node metastasis (including the presence of lymph node micrometastasis) suggested by postoperative pathological tests;
  3. Patients receiving neoadjuvant therapy are not allowed to have postoperative pathologic evidence of invasive carcinoma in the breast or axillary lymph nodes;

• Previous trastuzumab anti-HER-2 therapy: completion of ≥24 weeks (8 dosing cycles)

  of trastuzumab in the neoadjuvant and/or adjuvant phases; the interval between the end of the last course of trastuzumab therapy and entry into the study must be ≤1 year.

• Known hormone receptor status (ER/PR);
• ECOG score of 0-1;

Normal function of major organs:

1. Blood count:

   Neutrophils (ANC) ≥ 1.5 x 109/L; Platelet count (PLT) ≥90×109/L; Hemoglobin (Hb) ≥90 g/L;

2. Blood biochemistry:

   Total bilirubin (TBIL) ≤1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤1.5 × ULN; Alkaline phosphatase ≤ 2.5 x ULN; Urea or urea nitrogen (BUN) and creatinine (Cr) ≤ 1.5 × ULN;

3. Cardiac ultrasound:

   Left ventricular ejection fraction (LVEF) ≥55%;

4. 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) < 470 msec.
   • For female patients who are not menopausal or surgically sterilized: consent to abstinence or use of an effective non-hormonal pharmacologic method of contraception for the duration of treatment and for 8 weeks after the last dose of study treatment;
   • Benefit in the opinion of the investigator;
   • Voluntarily participate in the study by signing an informed consent form.

Exclusion Criteria:

• Confirmed local/regional recurrence/metastasis at enrollment;
• Prior anti-HER-2 therapy with pyrrolitinib, lenatinib, lapatinib and other tyrosine kinase inhibitors;
• History of gastrointestinal disease with diarrhea as the primary symptom;
• Psychiatric illness or psychotropic substance abuse that prevents cooperation;
• Female patients who are pregnant or breastfeeding;
• Those who, in the opinion of the investigator, are not suitable for enrollment.