Recruiting
Phase 2
Neoadjuvant SBRT Followed by Nab-Paclitaxel Combined With Toripalimab in HR+/HER2- Breast Cancer
Condition(s) studied
Breast Cancer
Investigational drug(s) / intervention(s)
Stereotactic Body Radiation Therapy (SBRT)Toripalimab →Neoadjuvant ChemotherapySurgeryAdjuvant ChemotherapyAdjuvant RadiotherapyEndocrine therapy
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.
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)
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).
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.
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)
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.
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.
Study summary
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).
Eligibility
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).
Primary outcome measure(s)
- Total pathologic complete response (tpCR) rate according to RCB system — 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.
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
Trial sites (2)
| Facility | City | Region | Status |
| Xijing Hospital Affiliated to Air Force Military Medical University |
Xi'an |
Shannxi Province |
Recruiting |
| Xijing Hospital Affiliated to Air Force Military Medical University |
Xi'an |
Shannxi |
Recruiting |
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