Recruiting

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

ClinicalTrials.gov IDNCT07457359

PhasePHASE2

Enrollment18

SponsorSecond Affiliated Hospital, Zhejiang University, School of Medicine

Age18 Years

SexFEMALE

I'm interested View official listing

Conditions studied

TNBC, Triple Negative Breast Cancer

About this study

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.

Interventions

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)

Primary outcomes

pCR rate (At definitive surgery, 3-5 weeks after completion of cycle 4 (week 15 from study entry))

Eligibility information

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.

Study locations

The Department of Radiation Oncology，the Second Affiliated Hospital of Zhejiang University School of Medicine, hangzhou, zhejiang, Hangzhou, China

Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.

Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.