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

NCT07457359 | Recruiting Phase 2 DMC

• 1 other identifier: Y2025-1398
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

TNBC, Triple Negative Breast Cancer

Keywords

chemo-resistance; neoadjuvant SBRT

Outcome Measures

Primary Outcomes (1)

• pCR rate

  Pathological complete response (pCR), percentage of patients with no invasive residual tumor in breast and lymph nodes (ypT0/is ypN0) at surgery.

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

Secondary Outcomes (2)

• ORR Rate

  After cycle 4, within 2 weeks before surgery (week 13).

• Acute and late toxicities

  From first SBRT fraction to 30 days post-SBRT (week 5); From first toripalimab dose to 90 days after last dose (week 28)

Study Arms (1)

SBRT-Toripalimab-Chemo Rescue

EXPERIMENTAL

All enrolled participants receive the same regimen: 1. Stereotactic Body Radiation Therapy (SBRT): started within 1 week after confirmation of chemotherapy resistance. 2. Toripalimab (anti-PD-1 antibody): cycle 1 starts the day after SBRT ends. 3. Chemotherapy switch: every 21 days for 4 cycles.

Radiation: SBRT; Drug: Toripalimab (anti-PD-1 antibody); Drug: Chemotherapy switch

Interventions

SBRT RADIATION

24 Gy in 3 daily fractions (8 Gy each) to the breast primary tumor, started within 1 week after confirmation of chemotherapy resistance.

SBRT-Toripalimab-Chemo Rescue

Toripalimab (anti-PD-1 antibody) DRUG

240 mg intravenous infusion every 21 days for 4 cycles

SBRT-Toripalimab-Chemo Rescue

Chemotherapy switch DRUG

Albumin-bound paclitaxel 125 mg/m² (days 1 \& 8) plus carboplatin AUC 6 (day 1)

SBRT-Toripalimab-Chemo Rescue

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

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

Hangzhou, China

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

toripalimab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Ting Zhang, phD.

CONTACT

+86-571-87783521; zezht@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2026
• First Posted: March 9, 2026
• Study Start: January 4, 2026
• Primary Completion (Estimated): January 4, 2028
• Study Completion (Estimated): January 4, 2029
• Last Updated: March 9, 2026

Record last verified: 2025-12

Locations

CN (1)