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

This is a single-arm, single-center, phase II exploratory trial designed for chemotherapy-refractory, early-stage triple-negative breast cancer (Stage II-III). After two cycles of standard neoadjuvant chemotherapy (taxane ± anthracycline ± platinum), patients with stable disease (SD) or progressive disease (PD) by RECIST 1.1 are eligible. Intervention sequence: Day 1-3: SBRT 8 Gy × 3 fractions to the intact breast primary (total 24 Gy) under daily image guidance. Day 4: first dose of toripalimab 240 mg IV. Day 21 (±3 d): start cycle 2 of toripalimab 240 mg d1 + albumin-bound paclitaxel 125 mg/m² d1,8 + carboplatin AUC 6 d1, q21 d × 4 cycles (immunotherapy always given first on day 1). Surgery: within 3-5 weeks after cycle 4; sentinel-node or axillary dissection per institutional standard. Adjuvant radiation (standard whole-breast/chest-wall plus nodal fields) is delivered post-operatively, but no further boost to the primary tumour bed is required. Endpoints Primary: pCR rate (ypT0/is ypN0) in the intent-to-treat population. Secondary: ORR by RECIST 1.1 after 4 cycles, change in TILs (H\&E-based, % stromal area), safety (CTCAE v5.0), event-free survival, overall survival, and rate of breast-conserving surgery. Exploratory: genomic scars, PD-L1, interferon signature, TCR clonality, ctDNA dynamics.