Pre‑surgery SBRT followed by nab‑paclitaxel plus toripalimab for HR+/HER2− breast cancer

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

This trial will test whether a short course of targeted radiotherapy before surgery, followed by reduced chemotherapy with nab‑paclitaxel and the immunotherapy toripalimab, can raise the chance of a complete tumor response in women with stage IIB–IIIC HR‑positive, HER2‑negative breast cancer.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 27 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Xijing Hospital (other)
• Drugs / interventions: Toripalimab, chemotherapy, immunotherapy
• Locations: 2 sites (Xi'an, Shannxi Province and 1 other locations)
• Trial ID: NCT06914440 on ClinicalTrials.gov

What this trial studies

This single‑arm Phase 2 trial will enroll 27 women with previously untreated, non‑metastatic stage IIB–IIIC HR+/HER2− breast cancer. Participants receive stereotactic body radiotherapy (SBRT) to the tumor area, then neoadjuvant nab‑paclitaxel combined with the PD‑1 inhibitor toripalimab, followed by surgery and planned adjuvant chemotherapy. The study uses pathology at surgery (pathological complete response, pCR) and safety assessments as primary endpoints to see whether adding radiotherapy and immunotherapy to de‑escalated chemotherapy increases pCR rates. Imaging, central pathology review, and standard labs will monitor response and toxicity throughout treatment and follow‑up.

Who should consider this trial

Good fit: Women aged 18–75 with previously untreated, non‑metastatic stage IIB–IIIC (cT3N0 or cT2‑4N1‑3) HR+/HER2− invasive breast cancer, ECOG 0–1, grade 2–3, Ki‑67 ≥15%, and deemed fit for radiotherapy and chemotherapy are ideal candidates.

Not a fit: Patients with metastatic disease, HER2‑positive or triple‑negative tumors, poor performance status, major comorbidities, or recent prior anticancer therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could increase pathological complete response rates and lower recurrence risk for higher‑risk HR+/HER2‑ breast cancer while potentially reducing overall chemotherapy exposure.

How similar studies have performed: Checkpoint inhibitors have shown clear benefit mainly in triple‑negative breast cancer, and smaller studies combining radiotherapy with immunotherapy have demonstrated immune activation but limited proven increases in pCR for HR+/HER2‑ disease, so this approach is promising but still experimental.

Eligibility criteria

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. Breast cancer assessed as non-metastatic (M0), meeting all of the following:

   1. Clinical stage: Stage IIB, IIIA, IIIB, or IIIC
   2. Required imaging assessments (within 28 days): Abdominal CT, ECT Bone scan, Chest CT and Brain MRI
4. Histologically or pathologically confirmed invasive carcinoma of no special type, 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).

Where this trial is running

Xi'an, Shannxi Province and 1 other locations

• Xijing Hospital Affiliated to Air Force Military Medical University — Xi'an, Shannxi Province, China (RECRUITING)
• Xijing Hospital Affiliated to Air Force Military Medical University — Xi'an, Shannxi, China (RECRUITING)

Study contacts

• Study coordinator: JIAJUN DING

Conditions: Breast Cancer, Neoadjuvant therapy