Neoadjuvant Chemotherapy in Combination With Toripalimab for HR+/HER2- Breast Cancer : a Randomized, Open-label, Parallel-controlled, Multi-center Phase III Study (NEOTORCH-BREAST04)

Neoadjuvant Chemotherapy in Combination With Toripalimab for HR+/HER2- Breast Cancer : a Randomized, Open-label, Parallel-controlled, Multi-center Phase III Study (NEOTORCH-BREAST04)

Our center plans to conduct a randomized, open-label, parallel-controlled, multi-center phase III study to evaluate the efficacy and safety of neoadjuvant chemotherapy combined with Toripalimab for HR+/HER2- breast cancer. The aim is to further explore the treatment strategy of chemotherapy with immunotherapy for patients with HR+/HER2- breast cancer, provide more treatment options for breast cancer patients, and offer a potential theoretical basis for the precision treatment of breast cancer.The primary study objective is to evaluate the pathologic complete response（PCR）and RCB0-1 ratio of neodjuvant treatment of HR+/HER2- breast cancer.

Inclusion Criteria:

1. Female patients aged 18-75 years old;

2. ECOG score is 0-1 points;

3. breast cancer meets the following standards: Histologically confirmed invasive breast cancer with tumor diameter>1cm (T1c-3; N0-3; M0). All patients were pathohistologically confirmed as HR+/HER2- breast cancer. According to the breast cancer diagnosis and treatment guidelines and specifications of the Chinese Anti Cancer Association (2021 version), Luminal B is divided into Luminal B (HER2 negative) and Luminal B (HER2 positive). Luminal B (HER2 negative) is ER/PR positive, HER2 negative and Ki-67 proliferation index is high or PR low expression. Luminal type B (HER2 positive) is ER/PR positive, HER2 positive (protein overexpression or gene amplification), and Ki-67 in any state. Therefore, HR+/HER2- breast cancer is a Luminal type breast cancer patient excluding HER2+.

   Pathological examination of PD-L1 expression:

   The Combined Positive Score (CPS) refers to the percentage of PD-L1 positive cells (including tumor cells, lymphocytes, macrophages) in all tumor cells. Our center detected the PD-L1 antibody site as 22C3.

4. The functional level of major organs must meet the following requirements (no blood transfusion within 2 weeks before screening, no use of...)

Using leukocyte and platelet boosting drugs:

1. Blood routine: Absolute neutrophil count (ANC) greater than 1.5 × 109/L; platelet count (PLT) greater than 75 × 109/L; Hemoglobin (Hb) is greater than 90g/L; Lymphocyte count ≥ 1.5 × 109/L
2. Blood biochemistry: Total bilirubin (TBIL) is less than 1.5 × ULN; Alanine aminotransferase ALT and aspartate levels are less than 1.5 × ULN; Alkaline phosphatase is less than 2.5 × ULN; Urea nitrogen/ Urea (BUN/UREA) and creatinine (Cr) are less than 1.5 × ULN.
3. Cardiac ultrasound: Left ventricular ejection fraction (LVEF) greater than 55%.
4. 12 lead electrocardiogram: The Fridericia corrected QT interval (QTcF) is less than 470 milliseconds 5. For female patients who have not yet reached menopause or undergone surgical sterilization: during the treatment period and in the study treatment, the final use effective contraceptive methods for at least 6 months after a single administration.

6. Voluntarily join this study, sign an informed consent form, have good compliance, and are willing to cooperate with follow-up.

Exclusion Criteria:

1. Stage IV breast cancer.
2. Inflammatory breast cancer.
3. Previously received anti-tumor treatment or radiation therapy for any malignant tumor, excluding those that have been cured Malignant tumors such as cervical carcinoma in situ, basal cell carcinoma, or squamous cell carcinoma.
4. Simultaneously undergoing anti-tumor treatment in other clinical trials, including but not limited to chemotherapy and endocrine therapy. Treatment, biological therapy, bone improvement drug therapy, or immune checkpoint inhibitor therapy, etc.
5. The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before the first administration of the study drug, or the patient has not fully recovered from such surgical procedures.
6. Serious heart disease or discomfort, including but not limited to the following diseases:

1) Diagnosed history of heart failure or systolic dysfunction (LVEF less than 50%).

2) High risk uncontrolled arrhythmias, such as atrial tachycardia, resting heart rate greater than 100bpm, significant ventricular arrhythmias (such as ventricular tachycardia), or higher-level atrioventricular block (i.e. Mobitz II second or third degree atrioventricular block).

3) Angina requiring medication for treatment. 4) Heart valve disease with clinical significance. 5) ECG shows transmural myocardial infarction. 6) Poor control of hypertension (systolic blood pressure greater than 180mmHg and/or diastolic blood pressure greater than 180mmHg after drug treatment) 100mmHg). 7. Uncontrolled active infections that require treatment; History of immunodeficiency, including HIV testing positive Sexual, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.

8. Patients with chronic active hepatitis B or active hepatitis C (excluding hepatitis B virus carriers, stable hepatitis B after drug treatment [HBV-DNA test negative or<50IU/ml] and cured hepatitis C patients [HCV RNA test negative]).

9. Have received immunotherapy and experienced adverse immune events such as immune related pneumonia and myocarditis, which have been determined by researchers to potentially affect the safety of the experimental medication.

10. Individuals with a known history of allergies to the components of this medication regimen.

11. Pregnant and lactating female patients, female patients with fertility and positive baseline pregnancy test results, or reproductive age patients who are unwilling to take effective contraceptive measures during the entire trial period and within 6 months after the last study medication.

12. Suffering from serious accompanying diseases or other comorbidities that may interfere with the planned treatment, or any other circumstances that the researcher deems unsuitable for the patient to participate in this study.