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

NCT06977893 | Recruiting Phase 3

• 1 other identifier: IIT20250026C
• Study Type: interventional
• Target: 194
• Locations: 1 country
• Sites: 13

Brief Summary

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.

Conditions

HR+/HER2- Breast Cancer

Keywords

Breast cancer; Toripalimab; Adjuvant Chemotherapy; Immunotherapy; HR-positive HER2-negative

Outcome Measures

Primary Outcomes (2)

• Pathologic Complete Response（PCR）

  The primary study objective is to evaluate the pathologic complete response（PCR） of the control group and experimental group.

  2 years

• RCB 0-1 Ratio

  2 years

Secondary Outcomes (2)

• Event Free Survival（EFS)

  5 years

• Objective Response Rate (ORR)

  5 years

Study Arms (2)

Experimental Group: Neoadjuvant Chemotherapy in Combination with Toripalimab

EXPERIMENTAL

Drug: Neoadjuvant Chemotherapy in Combination with Toripalimab Description: Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide, starting from the first day of the week, for a total of 12 weeks. Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks for a total of 12 weeks. During neoadjuvant chemotherapy and postoperative adjuvant therapy, use of Toripalimab: intravenous infusion of 240 mg, once every 3 weeks, combined with preoperative neoadjuvant and postoperative adjuvant therapy for a total of 1 year.

Drug: Neoadjuvant Chemotherapy in Combination with Toripalimab

Control Group: Neoadjuvant Chemotherapy

SHAM COMPARATOR

Drug: Neoadjuvant Chemotherapy Description: Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide, starting from the first day of the week, for a total of 12 weeks. Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks for a total of 12 weeks.

Drug: Neoadjuvant Chemotherapy

Interventions

Neoadjuvant Chemotherapy in Combination with Toripalimab DRUG

Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide, starting from the first day of the week, for a total of 12 weeks. Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks for a total of 12 weeks. During neoadjuvant chemotherapy and postoperative adjuvant therapy, use of Toripalimab: intravenous infusion of 240 mg, once every 3 weeks, combined with preoperative neoadjuvant and postoperative adjuvant therapy for a total of 1 year.

Experimental Group: Neoadjuvant Chemotherapy in Combination with Toripalimab

Neoadjuvant Chemotherapy DRUG

Epirubicin (or Liposomal Doxorubicin)+Cyclophosphamide, intravenous infusion of 100 mg/m2. Epirubicin (or 35 mg/m2 liposomal doxorubicin)+600 mg/m2 cyclophosphamide, starting from the first day of the week, for a total of 12 weeks. Paclitaxel, administered intravenously at a dose of 260 mg/m2 every 3 weeks for a total of 12 weeks.

Control Group: Neoadjuvant Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged 18-75 years old;
• ECOG score is 0-1 points;
• 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.
• 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:
• 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
• 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.
• Cardiac ultrasound: Left ventricular ejection fraction (LVEF) greater than 55%.
• 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.
• \. Voluntarily join this study, sign an informed consent form, have good compliance, and are willing to cooperate with follow-up.

You may not qualify if:

• Stage IV breast cancer.
• Inflammatory breast cancer.
• 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.
• 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.
• 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.
• Serious heart disease or discomfort, including but not limited to the following diseases:
• \) Diagnosed history of heart failure or systolic dysfunction (LVEF less than 50%).
• \) 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).
• \) 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.
• \. 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 \[HCV RNA test negative\]).
• \. 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.
• \. Individuals with a known history of allergies to the components of this medication regimen.
• \. 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.
• \. 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.

Sponsors & Collaborators

• First Affiliated Hospital of Zhejiang University: lead

Study Sites (13)

Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

Hangzhou, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhejiang University

Hangzhou, China

RECRUITING

Zhejiang Cancer Hospital

Hangzhou, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, China

NOT YET RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, China

NOT YET RECRUITING

Jinhua Municipal Central Hospital

Jinhua, China

NOT YET RECRUITING

Nanchang People's Hospital

Nanchang, China

NOT YET RECRUITING

Nantong First People's Hospital

Nantong, China

NOT YET RECRUITING

Zhongshan Hospitall, Fudan University

Shanghai, China

NOT YET RECRUITING

Xinjiang Medical University Affiliated Cancer Hospital

Ürümqi, China

NOT YET RECRUITING

Shaanxi Provincial Cancer Hospital

Xi'an, China

NOT YET RECRUITING

The Second Affiliated Hospital of Xi'an Jiaotong University

Xi'an, China

NOT YET RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

NOT YET RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Neoadjuvant Therapy; toripalimab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics

Central Study Contacts

Zhijun Dai, Professor

CONTACT

+86 157 0581 9132; dzj0911@126.com

Youyi Chen

CONTACT

+8615757515017; 913589289@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2025
• First Posted: May 18, 2025
• Study Start: March 24, 2025
• Primary Completion (Estimated): March 23, 2027
• Study Completion (Estimated): March 23, 2030
• Last Updated: May 18, 2025

Record last verified: 2025-05

Locations

CN (13)