NCT06914440

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Xijing Hospital · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

The goal of this clinical trial is to evaluate the efficacy and safety of neoadjuvant radiotherapy followed by chemotherapy combined with immunotherapy in patients with previously untreated stage IIB-IIIC (cT3N0 or cT2-4N1-3) HR-positive and HER2-negative breast cancer. 27 enrolled patients will be assigned to receive stereotactic body radiotherapy followed by Nab-Paclitaxel combined with Toripalimab. The main question it aims th answer is that whether the combination therapy of radiotherapy, de-escalated chemotherapy, and immunotherapy could improve the pCR rate of HR-positive and HER2-negative breast cancer.

Detailed description

HR-positive and HER2-negative (HR+/HER2-) breast cancer is the most common subtype of breast cancer. Although it is the subtype with the best treatment outcomes, HR+/HER2- breast cancer carries a higher risk of long-term recurrence and metastasis compared to the other subtypes. Additionally, patients with T3 or lager tumor or axillary lymph node metastasis have a significantly increased risk of local recurrence and distant metastasis compared to early-stage patients. 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 effectof 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.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2025-06-05
• Primary completion: 2026-04-01
• Completion: 2030-12-01
• First posted: 2025-04-06
• Last updated: 2025-07-15

Locations

2 sites across 1 country: China