Neoadjuvant Toripalimab Combined With Preoperative Radiotherapy for Initial Chemotherapy-Nonresponding Triple-Negative Breast Cancer Patients (NEOTRIO-2)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- pCR rate
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
- •ECOG performance status 0 or
- •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).
排除标准
- •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.
研究组 & 干预措施
SBRT-Toripalimab-Chemo Rescue
All enrolled participants receive the same regimen:
- Stereotactic Body Radiation Therapy (SBRT): started within 1 week after confirmation of chemotherapy resistance.
- Toripalimab (anti-PD-1 antibody): cycle 1 starts the day after SBRT ends.
- Chemotherapy switch: every 21 days for 4 cycles.
干预措施: SBRT (Radiation)
SBRT-Toripalimab-Chemo Rescue
All enrolled participants receive the same regimen:
- Stereotactic Body Radiation Therapy (SBRT): started within 1 week after confirmation of chemotherapy resistance.
- Toripalimab (anti-PD-1 antibody): cycle 1 starts the day after SBRT ends.
- Chemotherapy switch: every 21 days for 4 cycles.
干预措施: Toripalimab (anti-PD-1 antibody) (Drug)
SBRT-Toripalimab-Chemo Rescue
All enrolled participants receive the same regimen:
- Stereotactic Body Radiation Therapy (SBRT): started within 1 week after confirmation of chemotherapy resistance.
- Toripalimab (anti-PD-1 antibody): cycle 1 starts the day after SBRT ends.
- Chemotherapy switch: every 21 days for 4 cycles.
干预措施: Chemotherapy switch (Drug)
结局指标
主要结局
pCR rate
时间窗: At definitive surgery, 3-5 weeks after completion of cycle 4 (week 15 from study entry)
Pathological complete response (pCR), percentage of patients with no invasive residual tumor in breast and lymph nodes (ypT0/is ypN0) at surgery.
次要结局
- 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))