NCT07457359

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

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

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: Female
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• TNBC, Triple Negative Breast Cancer

Interventions

Type	Name	Description
RADIATION	SBRT	24 Gy in 3 daily fractions (8 Gy each) to the breast primary tumor, started within 1 week after confirmation of chemotherapy resistance.
DRUG	Toripalimab (anti-PD-1 antibody)	240 mg intravenous infusion every 21 days for 4 cycles
DRUG	Chemotherapy switch	Albumin-bound paclitaxel 125 mg/m² (days 1 \& 8) plus carboplatin AUC 6 (day 1)

Timeline

• Start date: 2026-01-04
• Primary completion: 2028-01-04
• Completion: 2029-01-04
• First posted: 2026-03-09
• Last updated: 2026-03-09

Locations

1 site across 1 country: China