To Evaluate the Efficacy of Toripalimab Combined With Chemotherapy After HIFU Induction in the Treatment of Early Triple-negative Breast Cancer

Study Overview
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Brief Summary
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To investigate the efficacy and safety of terbinumab combined with chemotherapy (epirubicin + cyclophosphamide → nab-paclitaxel + carboplatin) in neoadjuvant therapy of triple-negative breast cancer after HIFU.

Official Title
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To Evaluate the Efficacy and Safety of Toripalimab Combined With Chemotherapy (Epirubicin + Cyclophosphamide → Nab-paclitaxel + Carboplatin) in the Neoadjuvant Treatment of Triple-negative Breast Cancer After High-intensity Focused Ultrasound (HIFU) Induction

Conditions
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Breast Cancer, TNBC - Triple-Negative Breast Cancer

Intervention / Treatment
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* Drug: Toripalimab
* Drug: Epirubicin
* Procedure: High Intensity Focused Ultrasoun
* Drug: Cyclophosphamide
* Drug: Carboplatin
* Drug: Nab-paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients aged ≥ 18 years who require a negative pregnancy test for premenopausal and perimenopausal patients and promise to take reliable contraceptive measures during treatment; Histopathologically confirmed breast cancer patients who are negative for estrogen receptor (ER), progesterone receptor (PR), and HER-2 by immunohistochemistry; positive PD-L1 expression in tumor cells (≥ 1%); triple-negative breast cancer patients without distant metastasis; According to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, they have at least one evaluable target lesion; ECOG PS score: 0 - 1; New York Heart Association (NYHA) functional class I; Electrocardiogram without myocardial ischemia, echocardiography LVEF > 55%, cardiac markers: cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) test values within the normal range; Normal major organ function, Meet the following criteria: WBC ≥ 4.0 × 10 9/L,Neutrophil count (ANC) ≥ 1.5 × 10 9/L; platelet ≥ 100 × 10 9/L; hemoglobin ≥ 10 g/dL; serum creatinine ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) ≤ 2.5 × ULN; alanine aminotransferase (ALT) ≤ 2.5 × ULN; total bilirubin ≤ 1.5 × ULN; serum creatinine ≤ 1.5 × ULN; 9) The subject is able to understand the study procedures, voluntarily join the study, sign the informed consent form, have good compliance, and cooperate with the follow-up. - Exclusion Criteria: Patients during pregnancy and lactation, women of childbearing age who refuse to take effective contraceptive measures during the study period; Patients with peripheral nervous system disorders caused by diseases or those with a history of significant mental disorders and central nervous system disorders; Serious or uncontrolled infections that may affect the evaluation of study treatment or study results, including but not limited to: active hepatitis virus infection, human immunodeficiency virus (HIV) antibody positive, lung infection, etc.; Known allergy to the active ingredients or other components of the study drug or surgical contraindications; In addition to cured basal cell carcinoma of the skin and cured cervical carcinoma in situ, other cancers are disease-free for less than 5 years; Severe liver disease (such as cirrhosis, etc.), kidney disease, respiratory disease or uncontrolled diabetes, active gastrointestinal ulcers and other need treatment; Need to receive other anti-tumor therapy (except ovarian function inhibitors) during neoadjuvant therapy as judged by the investigator; Patients who are participating in other clinical trials within one month; Patients with severe heart disease or discomfort, Expected intolerance to chemotherapy,Including, but not limited to: a. fatal arrhythmia or higher grade atrioventricular block (second-degree type 2 [Mobitz 2] atrioventricular block or third-degree atrioventricular block); b. unstable angina pectoris; c. clinically significant valvular heart disease; d. transmural myocardial infarction on electrocardiogram; e. uncontrolled hypertension; any other condition that in the opinion of the investigator would make the patient inappropriate for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HIFU+Toripalimab+Chemotherapy<br>High Intensity Focused Ultrasoun， followed by Toripalimab 240 mg + epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2 × 4 cycles → Toripalimab240 mg + carboplatin AUC 5 + nab-paclitaxel 260 mg/m2 IVD × 4 cycles every 3 weeks for 8 doses. | Drug: Toripalimab<br>* Toripalimab 240mg<br>Drug: Epirubicin<br>* 90mg/m2，IVD，q3w<br>Procedure: High Intensity Focused Ultrasoun<br>* HIFU treatment at lesion site<br>Drug: Cyclophosphamide<br>* 600mg/m2，IVD，q3w<br>Drug: Carboplatin<br>* AUC 5，IVD，q3w<br>Drug: Nab-paclitaxel<br>* 260mg/m2，IVD，q3w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pCR | Pathologic complete response rate | 6 months |