Evaluate the Efficacy and Safety of Adebrelimab Combined With Chemotherapy With or Without Radiotherapy as Neoadjuvant Treatment for HER2-Negative Locally Advanced Breast Cancer

A Prospective, Multicenter, Randomized Controlled Phase II Study to Evaluate the Efficacy and Safety of Adebrelimab Combined With Chemotherapy With or Without Radiotherapy as Neoadjuvant Treatment for HER2-Negative Locally Advanced Breast Cancer

A Prospective, Multicenter, Randomized Controlled Phase II Study to Evaluate the Efficacy and Safety of Adebrelimab Combined with Chemotherapy with or without Radiotherapy as Neoadjuvant Treatment for HER2-Negative Locally Advanced Breast Cancer

Study Overview

• Status: Not yet recruiting
• Conditions: HER2-Negative Locally Advanced Breast Cancer
• Intervention / Treatment: Drug: Neoadjuvant Chemotherapy Combined with Immunotherapy and Radiotherapy; Drug: Neoadjuvant Chemotherapy Combined with Immunotherapy

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: fei Ma; Phone Number: 13910217780; Email: drmafei@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Female patients aged between 18 and 70 years old.
2. Pathologically confirmed as invasive breast cancer, with immunohistochemical staining indicating HER2 negativity, as specifically referenced in the guidelines of the American Society of Clinical
3. Oncology/College of American Pathologists (ASCO/CAP).
4. Clinical stage II-III, patients who are planned to undergo neoadjuvant treatment to downstage for surgery or who wish to have breast-conserving surgery after neoadjuvant treatment.
5. The breast tumor is suitable for SBRT (stereotactic body radiotherapy) (tumor distance from the skin > 5 mm, without invasion of the ribs or intercostal muscles).
6. No distant metastasis detected by clinical examination combined with imaging studies (including but not limited to liver ultrasound, chest CT, bone scan, PET-CT).
7. Adequate organ function (hemoglobin ≥ 100 g/L, white blood cells ≥ 3×10⁹/L, neutrophils ≥ 1.5×10⁹/L, platelets ≥ 80×10⁹/L; creatinine ≤ 132 μmol/L; alanine aminotransferase/aspartate aminotransferase ≤ 2.5×upper normal limit [UNL]).
8. Capable of undergoing breast magnetic resonance imaging (MRI) scans. Eligible for follow-up conditions.
9. The subject is able to sign the informed consent form to participate in the study.
10. Women of childbearing age are not pregnant, not breastfeeding, and are using effective contraception.

Exclusion Criteria:

1. Prior receipt of chest radiotherapy, chemotherapy, or immunotherapy.
2. History of other malignancies, with the exception of adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, or papillary thyroid cancer.
3. Patients with active fibroconnective tissue diseases, risk of active autoimmune diseases, or a history of autoimmune diseases that may involve the central nervous system, including but not limited to Crohn's disease, ulcerative colitis, systemic lupus erythematosus, sarcoidosis, Wegener's syndrome, granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, autoimmune hepatitis, systemic sclerosis, Hashimoto's thyroiditis, autoimmune vasculitis, and autoimmune neuropathies (e.g., Guillain-Barré syndrome). The following exceptions apply: Type I diabetes mellitus, stable hypothyroidism on hormone replacement therapy (including hypothyroidism due to autoimmune thyroid disease), psoriasis or vitiligo not requiring systemic therapy, and autoimmune diseases caused by B cells or anti-self-antigen antibodies.
4. Pulmonary disease defined as ≥ Grade 3 according to the NCI-CTCAE v5.0; history of interstitial lung disease (ILD) requiring corticosteroid treatment (including pulmonary fibrosis or radiation pneumonitis), or current ILD or ≥ Grade 2 radiation pneumonitis.

5. Severe comorbidities or active diseases:

   a) History of severe cardiovascular and cerebrovascular diseases, including but not limited to: i. Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, or third-degree atrioventricular block; ii. QT interval prolongation at rest (QTc > 450 msec in males or > 470 msec in females); iii. Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other Grade 3 or higher cardiovascular and cerebrovascular events within 6 months prior to the first dose; iv. Presence of heart failure with New York Heart Association (NYHA) functional class ≥ II.

   b) Poorly controlled diabetes for > 1 month: fasting blood glucose > 10 mmol/L, or postprandial 2-hour blood glucose > 13 mmol/L.

   c) Poorly controlled psychiatric disorders with an episode or exacerbation within the past 6 months.

   d) Active infection. e) Positive for human immunodeficiency virus (HIV) antibodies. Other diseases that are not suitable for immunotherapy, or a history of other malignancies.

6. Presence of severe internal medical conditions that may affect radiotherapy or immunotherapy.
7. Pregnant or breastfeeding women.
8. History of allergy to components of radiotherapy or immunotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant Chemotherapy Combined with Immunotherapy and Radiotherapy; Recommended Chemotherapy Regimen and Doses:Albumin-bound Paclitaxel 260 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles, followed by Epirubicin 90 mg/m² on Day 1 + Cyclophosphamide 600 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles.; Recommended Immunotherapy Dose:Adebrelimab 1200 mg, repeated every 3 weeks, starting simultaneously with neoadjuvant chemotherapy and continuing for 1 year (including postoperative administration).; Radiotherapy: Preoperative Radiotherapy: Positioning: Immobilization with a neck-chest integrated frame, combined CT and MRI positioning with image fusion. Diagnostic MRI images can also be fused simultaneously. CT positioning should be performed with a plain scan, with a slice thickness of 3 mm. MRI positioning should include at least three sequences: T1-enhanced, T2 fat-suppressed, and DWI. Target and Normal Organ Contouring: GTVp (Gross Tumor Volume - Primary): Define the breast tumor target area based on MRI, CT, physical examination, and ultrasoun	Drug: Neoadjuvant Chemotherapy Combined with Immunotherapy and Radiotherapy; Recommended Chemotherapy Regimen and Doses:Albumin-bound Paclitaxel 260 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles, followed by Epirubicin 90 mg/m² on Day 1 + Cyclophosphamide 600 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles.; Recommended Immunotherapy Dose:Adebrelimab 1200 mg, repeated every 3 weeks, starting simultaneously with neoadjuvant chemotherapy and continuing for 1 year (including postoperative administration).; Radiotherapy: Preoperative Radiotherapy: Positioning: Immobilization with a neck-chest integrated frame, combined CT and MRI positioning with image fusion. Diagnostic MRI images can also be fused simultaneously. CT positioning should be performed with a plain scan, with a slice thickness of 3 mm. MRI positioning should include at least three sequences: T1-enhanced, T2 fat-suppressed, and DWI. Target and Normal Organ Contouring: GTVp (Gross Tumor Volume - Primary): Define the breast tumor target area based on MRI, CT, physical examination, and ultrasound
Active Comparator: Neoadjuvant Chemotherapy Combined with Immunotherapy; Recommended Chemotherapy Regimen and Doses:Albumin-bound Paclitaxel 260 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles, followed by Epirubicin 90 mg/m² on Day 1 + Cyclophosphamide 600 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles.; Recommended Immunotherapy Dose: Adebrelimab 1200 mg, repeated every 3 weeks, starting simultaneously with neoadjuvant chemotherapy and continuing for 1 year (including postoperative administration).	Drug: Neoadjuvant Chemotherapy Combined with Immunotherapy; Recommended Chemotherapy Regimen and Doses:Albumin-bound Paclitaxel 260 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles, followed by Epirubicin 90 mg/m² on Day 1 + Cyclophosphamide 600 mg/m² on Day 1, every 3 weeks (Q3W) × 4 cycles.; Recommended Immunotherapy Dose: Adebrelimab 1200 mg, repeated every 3 weeks, starting simultaneously with neoadjuvant chemotherapy and continuing for 1 year (including postoperative administration).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR)	For binary efficacy endpoints (including pCR, ORR, etc.), the number of subjects and percentage in each category will be summarized, and the 95% confidence interval for the rate will be calculated using the Clopper-Pearson method.	24 months

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2025
• Primary Completion (Estimated): September 10, 2028
• Study Completion (Estimated): September 10, 2028

Study Registration Dates

• First Submitted: March 18, 2025
• First Submitted That Met QC Criteria: April 1, 2025
• First Posted (Actual): April 3, 2025

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: April 1, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Immunomodulating Agents; Immunologic Factors
• Other Study ID Numbers: NCC5177

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No