Neoadjuvant SBRT Followed by Nab-Paclitaxel Combined With Toripalimab in HR+/HER2- Breast Cancer

Neoadjuvant SBRT Followed by Nab-Paclitaxel Combined With Toripalimab in HR+/HER2- Breast Cancer: A Single-arm, Prospective Clinical Trial

The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant stereotactic body radiotherapy (SBRT) followed by nab-paclitaxel combined with toripalimab in patients with previously untreated HR+/HER2-negative breast cancer. Eligible patients include those with stage IIB-IIIC disease (cT3N0, cT2-4N1-3 or cT1N2-3) or stage IIA disease (cT2N0 or cT1N1) with at least two of the following high-risk factors: histologic grade 3, Ki-67 ≥50% or premenopausal with age <50 years. A total of 27 enrolled patients will be assigned to receive the combination therapy. The primary question it aims to answer is whether this combination of radiotherapy, de-escalated chemotherapy, and immunotherapy can improve the total pathologic complete response (tpCR) rate (defined as ypT0/Tis ypN0).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Radiation: Stereotactic Body Radiation Therapy (SBRT); Drug: Toripalimab; Drug: Neoadjuvant Chemotherapy; Procedure: Surgery; Drug: Adjuvant Chemotherapy; Radiation: Adjuvant Radiotherapy; Drug: Endocrine therapy

Detailed Description

HR-positive and HER2-negative (HR+/HER2-) breast cancer is the most common subtype of breast cancer. Although this subtype is generally associated with favorable overall survival, patients with high-risk features remain at substantial risk for late recurrence and distant metastasis. In particular, those presenting with large primary tumors (cT3 or higher) or axillary lymph node involvement face a significantly elevated risk of locoregional recurrence and distant metastasis relative to patients with earlier-stage, lower-risk disease.

In recent years, the role of neoadjuvant therapy in the comprehensive treatment of breast cancer has gained increasing attention. The pathological complete response (pCR) rate following neoadjuvant therapy is closely associated with long-term survival. However, compared to HER2+ or triple-negative breast cancer, HR+/HER2- breast cancer patients exhibit a significantly lower pCR rate with neoadjuvant chemotherapy alone. Neoadjuvant chemotherapy combined with immunotherapy has become a key treatment strategy for TNBC, this combination also improves pCR rates in HR+/HER2- breast cancer, though the benefit is less pronounced than in TNBC. Radiotherapy not only releases a large number of tumor antigens and inflammatory signals to enhance systemic anti-tumor immune responses, but also promotes the exposure of tumor cell surface antigens, thereby increasing the immunogenicity of the tumor microenvironment. The synergistic effect of radiotherapy and immunotherapy, when combined with chemotherapy, may further improve treatment efficacy. Based on these, we designed this clinical trial evaluating the effect of neoadjuvant radiotherapy combined with de-escalated chemotherapy and immunotherapy, aiming to explore its potential to improve pCR rates and long-term outcomes in HR+/HER2- breast cancer patients. Enrolled patients will receive four cycles of single-agent Nab-Paclitaxel plus Toripalimab within one week after stereotactic radiotherapy, followed by surgery and subsequent adjuvant therapy. Postoperative pCR rate and prognosis of participants will be analyzed in our clinical study.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: JIAJUN DING; Phone Number: 15121089323; Email: yuki_ding1996@163.com

Study Locations

• China
  • Shannxi
    • Xi'an, Shannxi, China
      • Recruiting
      • Xijing Hospital Affiliated to Air Force Military Medical University
      • Contact: Ting Wang; Phone Number: 0086-13700283101; Email: ting_w100@126.com
  • Shannxi Province
    • Xi'an, Shannxi Province, China, 710032
      • Recruiting
      • Xijing Hospital Affiliated to Air Force Military Medical University
      • Contact: Ting Wang, PhD; Phone Number: 0086-13700283101; Email: ting_w100@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female patients aged ≥18 and ≤75 years at the time of signing informed consent.
2. ECOG PS status of 0-1.

3. Histologically confirmed non-metastatic (M0) breast cancer, meeting all of the following:

   a) Clinical stage (per AJCC 8th edition) meeting one of the following: i. cT3N0, cT2-4N1-3, or cT1N2-3 (Stage IIB, IIIA, IIIB, or IIIC); ii. cT2N0 or cT1N1 (Stage IIA) with at least two of the following high-risk features: Histologic grade 3; Ki-67 ≥50%; Age <50 years and premenopausal status.

   b) Imaging assessments within 28 days prior to enrollment including: abdominal CT or ultrasound, bone scan (ECT), chest CT, and brain MRI.

4. Histologically or pathologically confirmed invasive carcinoma, with all of the following:

   1. Grade 2 or 3 (confirmed by central laboratory);
   2. ER-positive (>1% staining) and/or PR-positive (>1% staining) by IHC;
   3. HER2-negative (IHC 0/1+ or HER2/neu FISH ratio ≤1.8);
   4. Ki-67 ≥15%.
5. Patient deemed eligible for radiotherapy after MDT evaluation.
6. No prior antitumor therapy within 1 month before enrollment.

7. Organ Function Requirements (within 7 days prior to enrollment):

   1. Complete blood count (no transfusion or hematopoietic growth factors within 7 days): ANC ≥1.5×10⁹/L; ALC ≥0.5×10⁹/L; Platelets ≥100×10⁹/L; Hemoglobin ≥90 g/L; WBC ≥3.0×10⁹/L and ≤15×10⁹/L;
   2. Blood biochemistry (no transfusion/albumin within 7 days): ALT/AST ≤2.5×ULN; ALP ≤2.5×ULN；BUN/Cr ≤1.5×ULN; Cr≥60 mL/min (Cockcroft-Gault formula);
   3. Coagulation: PT/APTT ≤1.5×ULN; INR ≤1.5×ULN (if no anticoagulant therapy);
   4. Urinalysis: Urine protein <2+; if ≥2+, 24-hour urine protein must be ≤1g;
   5. Thyroid function:TSH ≤1×ULN; if abnormal, normal T3/T4 levels required for eligibility.

8. Women of childbearing potential must:

   1. Have a negative serum pregnancy test within 7 days before treatment;
   2. Use highly effective contraception during the study and for 180 days after the last dose.
9. Voluntarily sign informed consent, demonstrate good compliance, and commit to follow-up.

Exclusion Criteria:

1. Inflammatory Breast Cancer.

2. Comorbidities/Medical History:

   1. Autoimmune disease: patients with any known or suspected autoimmune disease, except: hypothyroidism due to autoimmune thyroiditis managed with hormone replacement therapy only, stable type-1 diabetes with well-controlled blood glucose.
   2. Cardiovascular Diseases: poorly controlled hypertension despite medication (SBP >140 mmHg or DBP>90 mmHg). And with the history (within 6 months prior to enrollment) of myocardial infarction, severe/unstable angina, NYHA Class ≥2 heart failure, clinically significant arrhythmias as well as symptomatic congestive heart failure.
   3. Interstitial lung disease, non-infectious pneumonitis, or other uncontrolled systemic diseases (e.g., diabetes, pulmonary fibrosis, acute pneumonia);
   4. Vaccination: receipt of live attenuated vaccines within 28 days prior to enrollment or planned during the study;
   5. Infections: HIV/AIDS, active hepatitis(HBV-DNA ≥500 IU/mL; HCV-RNA above detection limit), or co-infection with HBV and HCV, severe infections within 4 weeks prior to enrollment (e.g., bacteremia, severe pneumonia requiring hospitalization), active infection requiring systemic antibiotics (CTCAE≥Grade 2) within 2 weeks prior to treatment, active tuberculosis within 1 year prior to enrollment;
   6. Unexplained fever >38.5°C during screening (unless deemed tumor-related by the investigator);
   7. Malignancy History: other malignancies diagnosed within 5 years prior to enrollment (except adequately treated basal cell carcinoma, squamous cell skin cancer, or cervical carcinoma in situ);
   8. Surgery:Major surgery within 28 days prior to enrollment (diagnostic biopsies or PICC line placement are allowed);
   9. Transplant: Prior or planned allogeneic bone marrow or solid organ transplant;
   10. Neurological: peripheral neuropathy ≥Grade 2;
   11. Gastrointestinal: clinically significant bowel obstruction;
   12. Thrombotic Events: arterial/venous thrombosis within 6 months prior to enrollment (e.g., stroke, transient ischemic attack, DVT, pulmonary embolism);
   13. Bleeding Risk: hemoptysis (≥2.5 mL/day) within 2 months prior to enrollment, clinically significant bleeding within 3 months prior to enrollment (e.g. gastrointestinal bleeding, hemorrhagic gastric ulcer, baseline fecal occult blood≥++), and the known bleeding/thrombotic disorders (e.g., hemophilia, coagulopathy, thrombocytopenia, hypersplenism);
   14. Coagulation abnormalities (INR >1.5×ULN or APTT >1.5×ULN), or requiring long-term anticoagulation (warfarin/heparin) or antiplatelet therapy (aspirin≥300 mg/day or clopidogrel ≥75 mg/day).

3. Treatment-Related Exclusions:

   1. Prior systemic targeted therapy or immunostimulants (e.g., interferon, IL-2) within 4 weeks before treatment;
   2. Known allergy to the investigational drug (recombinant humanized anti-PD-1 mAb) or its excipients.
4. Clinical Trial Participation: participation in another drug trial within 4 weeks prior to enrollment, or within 5 half-lives of the last investigational drug dose.
5. Substance Abuse: history of drug/alcohol abuse or dependency.
6. Pregnancy/Lactation: pregnant, breastfeeding, or planning pregnancy during the study.
7. Investigator' s Discretion: other conditions that may compromise subject safety or study integrity (e.g., severe lab abnormalities, social factors).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment; During the neoadjuvant treatment period, participants will undergo stereotactic radiotherapy and subsequently receive chemotherapy combined with immunotherapy.

Radiation: Stereotactic Body Radiation Therapy (SBRT); The prescribed dose of radiation is 24 Gy delivered in 3 fractions (8 Gy/fraction) using SBRT technique. Subjects received SBRT for the primary breast cancer lesion at 8Gy/Fraction each time for 3 consecutive days, 1 week before the start of systemic therapy. The first day of radiation is C1D1.; Drug: Toripalimab; Toripalimab will be administered at a fixed dose of 240 mg via intravenous infusion every 3 weeks (q3w). The first dose is given on Cycle 2 Day 1 (C2D1), followed by dosing on the first day of each subsequent cycle for a total of 4 cycles. (Toripalimab×4 240mg D1 q3w); Drug: Neoadjuvant Chemotherapy; Combined with Toripalimab, Nab-paclitaxel will be dosed at 125 mg/m² based on body surface area, administered by intravenous infusion weekly (Days 1, 8, 15 of each 21-day cycle) for 4 cycles.(T×4, Nab-Paclitaxel 125mg/m2，D1、D8、D15 q3w).; Procedure: Surgery; Surgery will be performed 2-6 weeks after completion of neoadjuvant therapy. The surgical approach will be determined by the investigator based on disease status and patient preference.; Drug: Adjuvant Chemotherapy; The anthracycline may be either Epirubicin (body surface area-adjusted 50 mg/m²) or Liposomal Doxorubicin (body surface area-adjusted 30 mg/m²) combined with Cyclophosphamide (body surface area-adjusted 600 mg/m²). Both drugs were administered intravenously every 3 weeks, and then the first day of each course was administered for 4 cycles. (EC×4, Epirubicin 50 mg/m² or Liposomal Doxorubicin 30 mg/m², comined with Cyclophosphamide 600 mg/m², D1, q3w); Radiation: Adjuvant Radiotherapy; Conventional radiotherapy will be delivered to the breast/chest wall and regional lymph nodes (investigator-selected technique), with explicit prohibition of tumor bed boost irradiation.; Drug: Endocrine therapy; Investigator-selected adjuvant endocrine therapy will be deterimend according to applicable guidelines, considering menopausal status, recurrence risk, treatment history, comorbidities as well as patient preference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total pathologic complete response (tpCR) rate according to RCB system	tpCR is defined as the absence of invasive carcinoma in the breast primary lesion and negative regional lymph nodes (ypT0/Tis ypN0) by hematoxylin-eosin staining after completion of the neoadjuvant treatment. RCB system will be used for the pathological evaluation after neoadjuvant therapy	At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RCB 0/I rate	The RCB 0/I rate is defined as the percentage of patients achieving either pathological complete response (RCB-0) or minimal residual disease (RCB-I), corresponding to near-pCR status	At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
Breast pathologic complete response (bpCR) rate	bpCR is defined as the absence of residual invasive carcinoma in the breast primary lesion (ypT0/Tis; ductal carcinoma in situ may be present), regardless of regional lymph node status, assessed by hematoxylin and eosin (H&E) staining after neoadjuvant therapy.	At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
Axillary pathologic complete response (apCR) rate	apCR is defined as negative pathologic status of axillary lymph nodes (ypN0) after neoadjuvant therapy, assessed by H&E staining.	At definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab (each cycle is 21 days), approximately 4 months from start of neoadjuvant therapy.
Objective response rate (ORR)	ORR is defined as the proportion of patients with best overall response of complete response (CR) or partial response (PR) per RECIST version 1.1, as assessed by the investigator.	From start of neoadjuvant therapy until definitive surgery, assessed every 2 cycles (each cycle is 21 days) during neoadjuvant treatment.
EFS	Event-free survival (EFS) is defined as the time from the first neoadjuvant treatment to the first occurrence of any of the following events: (1) disease progression during neoadjuvant therapy (locoregional progression or distant metastasis) precluding radical surgery; (2) locoregional recurrence or distant metastasis after definitive surgery; (3) second primary malignancy; or (4) death from any cause.	From date of first neoadjuvant treatment until the date of first documented event, assessed up to 5 years.
iDFS	Invasive disease-free survival (iDFS) is defined as the time from the first neoadjuvant treatment to invasive disease recurrence (including local recurrence, ipsilateral and contralateral invasive breast cancer, distant recurrence), new primary tumor, or death from any cause.	From date of first neoadjuvant treatment until the date of first documented invasive disease recurrence or death, assessed up to 5 years.
OS	Overall survival (OS) is defined as the time from the first neoadjuvant treatment to death from any cause.	From date of first neoadjuvant treatment until the date of death from any cause, assessed up to 5 years.
Safety and tolerability	Incidence, severity, and type of treatment-related adverse events (AEs) and serious adverse events (SAEs), graded according to NCI CTCAE version 5.0.	From signing of informed consent through 30 days after the last dose of study treatment, assessed up to 5 years.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) with efficacy	To evaluate the association between baseline PD-L1 expression status (by IHC) and TILs density (by HE staining and IHC) in pre-treatment tumor tissue and pathologic response (tpCR, RCB 0/I, bpCR, apCR)	PD-L1 and TILs will be evaluated at baseline (pre-treatment), and pathologic response will be assessed at definitive surgery (approximately 4 months after initiation of neoadjuvant therapy).
Effect of treatment on the immune microenvironment of HR+/HER2- breast cancer	To explore the percentage change (unit of measure: percentage of positive cells and relative expression change) in tumor immune microenvironment markers (e.g., immune cell infiltration, PD-L1 expression) induced by neoadjuvant treatment, assessed by IHC in paired pre- and post-treatment tumor tissue samples.	Baseline (pre-treatment) and perioperative (at definitive surgery, following completion of neoadjuvant SBRT and 4 cycles of nab-paclitaxel plus toripalimab, each cycle is 21 days, approximately 4 months).

Collaborators and Investigators

• Sponsor: Xijing Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: March 30, 2025
• First Submitted That Met QC Criteria: March 30, 2025
• First Posted (Actual): April 6, 2025

Study Record Updates

• Last Update Posted (Actual): August 14, 2026
• Last Update Submitted That Met QC Criteria: August 12, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Breast Cancer; Neoadjuvant therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Investigative Techniques; Therapeutics; Drug Therapy; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Combined Modality Therapy; toripalimab; Surgical Procedures, Operative; Radiosurgery; Neoadjuvant Therapy; Chemotherapy, Adjuvant; Radiotherapy, Adjuvant
• Other Study ID Numbers: XJ-ViBranT-B-001

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