Trastuzumab Emtansine (T-DM1) in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy

Trastuzumab Emtansine (T-DM1) Treatment in HER2-positive Breast Cancer Patients With Progressive Disease After TKIs or HP Therapy: a Multicenter, Single-arm, Phase II Study

The goal of this clinical trial is to learn about the efficacy and safety of trastuzumab emtansine (T-DM1) in the treatment of patients with advanced HER2-positive breast cancer after TKIs or HP therapy. The main questions it aims to answer are:

• The objective response rate of patients receiving T-DM1 therapy with advanced HER2-positive breast cancer after TKIs or HP therapy.
• The adverse events and prognosis of patients with advanced HER2-positive breast cancer who receive the T-DM1 therapy.
• Changes of anti-tumor immunity during T-DM1 therapy in patients with advanced HER2-positive breast cancer.

Participants will receive T-DM1 treatment (3.6mg/kg, d1/21, IVD) until progressive diseases or intolerable adverse effects occurs.

Inclusion Criteria:

• Age ≥ 18 years; pregnancy test (-) for premenopausal and perimenopausal patients, promising to use reliable contraception during treatment.
• Patients who were be diagnosed with invasive breast cancer according to the eighth edition of American Joint Committee on Cancer (AJCC) staging system, and develop disease progression after anti-HER2 therapy (TKIs) for stage IV disease at initial diagnosis or within one year of adjuvant anti-HER2 therapy (HP) after surgery for early breast cancer.
• At least one measurable lesion according to RECIST 1.1.
• ECOG score of 0 or 1.
• The organ function is still good and meets the following indicators: hemoglobin ≥ 90g/L, white blood cell ≥ 3.5×10^9/L, platelet ≥ 100×10^9/L, neutrophil ≥ 1.5×10^9/L, aspartate aminotransferase or alanine aminotransferase ≤ 3×ULN, total bilirubin ≤ 1.5×ULN, serum creatinine value ≤ 1.5×ULN.
• Without myocardial ischemia in ECG.
• NYHA grade I; Echocardiography LVEF ≥55%; Cardiac markers: cardiac troponin (cTnI) and brain natriuretic peptide (BNP) within normal range.
• Complete all necessary baseline laboratory and radiological tests prior to treatment.
• Complete clinical data.

Exclusion Criteria:

• male breast cancer or inflammatory breast cancer.
• Patients who have other malignant tumors or have contracted malignant tumors other than breast cancer in the past 5 years, except for basal cell carcinoma of the skin or flat cell carcinoma and carcinoma in situ of the cervix that have been adequately treated and controlled.
• Accompanying other anti-tumor treatments or participating in other clinical trials.
• Serious diseases that will affect the patient's compliance or put the patient at risk.
• Major surgical procedures performed within 4 weeks prior to the commencement of study treatment or anticipated major surgical procedures during the course of the study.
• Patients who have used ADC drugs at present or before this study.
• History of allergic reactions or contraindications to use of any drug ingredient in this study.
• Patients with chronic diarrhea and intestinal obstruction, as well as other diseases that affect drug administration and absorption.
• Patients who have clinical cardiac symptoms or diseases that are not well controlled, such as: heart failure above NYHA 2; unstable angina; myocardial infarction occurred within one year; clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention.
• Dementia, intellectual abnormality, or any mental illness that interferes with the understanding of informed consent.