HER2-positive Breast Cancer Project Initiated by Investigators

An Open-clinical Trial Phase Ⅱ, Injection of A166 for HER2-positive Patients With Refractory Unresectable Locally Advanced or Metastatic Breast Cancer；KL166-IIS-001

This study will assess the objective response rate (ORR), safety, progression-free survival (PFS) , overall survival (OS), 6-month survival rate, 12-month survival rate, 18-month survival rate, 24-month survival rate, disease control rate (DCR), clinical benefit rate (CBR), duration of response (DOR) and Time to Response (TTR). Injection of A166 for HER2-positive patients with refractory unresectable locally advanced or metastatic breast cancer who have failed previous ADC drug therapy.

Inclusion Criteria:

• 1. Male or female patient ≥ 18 years and ≤ 75 years when signing the informed consent form; 2. Breast cancer patients by histopathology and/or cytology documented, including:

  a) Participants with unresectable locally advanced or metastatic breast cancer; b) Evaluated or tested as HER2-positive expression. The definition of HER2 positive in this study: immunohistochemistry (IHC) was 2+ and confirmed by fluorescence in situ hybridization (FISH), or IHC was 3+; 3. Have received at least 3 targeted therapies for locally advanced or metastatic disease, including:

  1. Disease progression after receiving at least 1 trastuzumab-containing (including a biosimilar of trastuzumab on the market)-based treatment;

  2. After receiving at least one anti-HER2 tyrosine kinase inhibitor (lapatinib or pyrrotinib)-based treatment plan, the disease progresses or cannot tolerate toxic and side effects;

  3. The disease progresses or cannot tolerate toxic and side effects after receiving treatment with antibody-conjugated drugs targeting HER2 (such as T-DM1 or other ADCs); Note: Adjuvant therapy and anti-HER2 therapy used in the neoadjuvant treatment stage before radical treatment are not counted, but recurrence or metastasis occurs during the last anti-HER2 medication period or within one year after the end, it can be regarded as a plan.

     4. Have previously received taxanes to treat breast cancer;

     Exclusion Criteria:

• 1. Serious or uncontrollable heart diseases that require treatment, including:

  1. Congestive heart failure graded 3 or 4 by the New York College of Cardiology (NYHA);
  2. Unstable angina pectoris that cannot be controlled by drugs;
  3. Myocardial infarction occurred within 6 months before the first administration of the study treatment;
  4. Severe arrhythmia requiring medical treatment (except for atrial fibrillation or paroxysmal supraventricular tachycardia); 2. Baseline measurement, QTc interval, male> 450 msec, female> 470 msec; 3. Clinically active interstitial lung disease; 4. Patients with primary central nervous system (CNS) malignant tumors or CNS metastases that have failed local treatment; for asymptomatic brain metastases, or with stable clinical symptoms and no need for steroids and other brain metastases within 4 weeks before the first administration of the trial drug Treated patients can be included in the group; 5. Those who are known to have a history of hypersensitivity to other monoclonal antibodies or allergic to A166 and its components for injection; 6. Those who have permanently discontinued trastuzumab due to any toxicity;