Short-course SBRT plus toripalimab and chemotherapy for chemo-resistant triple-negative breast cancer

Neoadjuvant Toripalimab Combined With Preoperative Radiotherapy for Initial Chemotherapy-Nonresponding Triple-Negative Breast Cancer Patients (NEOTRIO-2)

This trial will try a short, high-precision course of breast radiation followed by toripalimab with paclitaxel and carboplatin for people whose triple-negative breast cancer did not shrink after initial chemotherapy to see if it can eliminate invasive cancer at surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 75 Years
• Sex: Female
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: toripalimab, chemotherapy, Radiation, prednisone, immunotherapy
• Locations: 1 site (Hangzhou)
• Trial ID: NCT07457359 on ClinicalTrials.gov

What this trial studies

This is a single-arm, single-center Phase II trial for patients with stage II–III triple-negative breast cancer whose tumors show stable or progressive disease after two cycles of standard neoadjuvant chemotherapy. Participants receive stereotactic body radiotherapy (24 Gy in 3 daily fractions) to the intact breast primary, then start toripalimab with albumin-bound paclitaxel and carboplatin for four 21-day cycles. The primary endpoint is pathologic complete response (no invasive cancer in breast or nodes at surgery), with secondary endpoints including objective radiologic response, changes in tumor-infiltrating lymphocytes, safety, event-free and overall survival, and rate of breast-conserving surgery. Exploratory biomarker studies include whole-exome and RNA sequencing, TCR clonality, PD-L1 and interferon signatures, and circulating tumor DNA dynamics.

Who should consider this trial

Good fit: Ideal candidates are women aged 18–75 with newly diagnosed stage II–III triple-negative breast cancer who have stable or progressive disease after two cycles of standard neoadjuvant chemotherapy, have ECOG 0–1, adequate organ function, and are suitable for SBRT and surgery.

Not a fit: Patients who already respond to initial chemotherapy, have distant metastatic disease, poor performance status, or contraindications to radiotherapy, immunotherapy, or platinum/taxane chemotherapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could convert chemotherapy-resistant tumors into pathologic complete responses and increase the chance of breast-conserving surgery.

How similar studies have performed: Combining radiotherapy with PD‑1 blockade has shown promising signals in early-phase studies, but this specific SBRT followed by toripalimab plus chemotherapy 'rescue' strategy is novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

* Female, age 18-75 years, newly diagnosed invasive breast cancer.
* Histologically confirmed triple-negative phenotype: ER \< 1 %, PR \< 1 % by IHC, HER2 negative (IHC 0/1+ or IHC 2+ with ISH negative).
* Clinical stage II-III (T2-4 or N1-3, M0).
* Completed 2 cycles of standard neoadjuvant chemotherapy (taxane ± anthracycline ± platinum) and assessed as non-responder: stable disease (SD) or progressive disease (PD) by RECIST 1.1.
* ECOG performance status 0 or 1.
* Radiation oncologist confirms suitability for SBRT and subsequent standard post-operative radiotherapy.
* Adequate organ function within 14 days before enrollment: WBC ≥ 2 000/µL, ANC ≥ 1 500/µL, platelets ≥ 100 000/µL, Hb ≥ 9 g/dL; Serum creatinine ≤ 2 mg/dL or GFR ≥ 40 mL/min; AST/ALT ≤ 2.5 × ULN, total bilirubin ≤ ULN (≤ 3 mg/dL if Gilbert syndrome); INR ≤ 1.5 (on anticoagulation allowed if therapeutic range)
* Negative HIV, HBV surface antigen, and HCV antibody (or HBV DNA / HCV RNA negative if false-positive).

Exclusion Criteria:

* Inflammatory breast cancer.
* Any other malignancy requiring treatment within the past 3 years (except adequately treated basal-cell skin carcinoma or cervical CIS).
* Active autoimmune disease, immunodeficiency, or systemic steroids \> 10 mg/day prednisone equivalent within 2 years.
* Clinically significant cardiovascular disease (unstable angina, NYHA III/IV heart failure, recent MI).
* Prior radiotherapy to the breast or chest wall.
* Active infection requiring systemic therapy.
* Known intolerance or hypersensitivity to toripalimab, paclitaxel, or carboplatin.
* Pregnant or lactating women.

Where this trial is running

Hangzhou

• The Department of Radiation Oncology，the Second Affiliated Hospital of Zhejiang University School of Medicine, hangzhou, zhejiang — Hangzhou, China (Recruiting)

Study contacts

• Study coordinator: Ting Zhang, phD.

Conditions TNBC, Triple Negative Breast Cancer; chemo-resistance; neoadjuvant SBRT