Neoadjuvant Toripalimab Plus SBRT for Chemo-Resistant Triple-Negative Breast Cancer

Summary

The goal of this clinical trial is to test whether a "rescue" strategy can turn chemotherapy-resistant triple-negative breast cancer (TNBC) into a curable state. Patients whose tumors fail to shrink after 2 cycles of standard neoadjuvant chemotherapy will receive a short, high-precision course of stereotactic body radiotherapy (SBRT, 24 Gy in 3 daily fractions) to the breast primary tumor, followed by 4 cycles of toripalimab (an anti-PD-1 antibody) combined with albumin-bound paclitaxel plus carboplatin. The main questions are: Can this SBRT-immuno-chemo triplet raise the pathologic complete response (pCR; no invasive cancer in breast or nodes at surgery)? Can it produce an objective radiologic response (ORR) in at least half of the patients, allowing more breast-conserving operations and fewer mastectomies? Secondary objectives include safety, changes in tumor-infiltrating lymphocytes (TILs), event-free survival, and exploratory biomarkers (whole-exome and RNA-seq, PBMC immunoprofiling) to discover signatures of benefit. Participants will undergo image-guided core biopsies before and after SBRT, provide serial blood samples, and have definitive surgery 3-5 weeks after the last cycle.

Eligibility

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.

Conditions3

Interventions2

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