TNBC, Triple Negative Breast CancerPhase 2NEOTRIO-2NCT07457359
Neoadjuvant Toripalimab Plus SBRT for Chemo-Resistant Triple-Negative Breast Cancer
A Phase 2 study testing SBRT, Toripalimab (anti-PD-1 antibody) and Chemotherapy switch in people with TNBC, Triple Negative Breast Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- TNBC, Triple Negative Breast Cancer
- What is being tested?
- SBRT, Toripalimab (anti-PD-1 antibody) and Chemotherapy switch
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 4 Jan 2026to 4 Jan 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
The Department of Radiation Oncology，the Second Affiliated Hospital of Zhejiang University School of Medicine, hangzhou, zhejiang
Hangzhou
About this study
Official title: Neoadjuvant Toripalimab Combined With Preoperative Radiotherapy for Initial Chemotherapy-Nonresponding Triple-Negative Breast Cancer Patients (NEOTRIO-2)
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.
Read the 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
- Being tested
- SBRT, Toripalimab (anti-PD-1 antibody), Chemotherapy switch
- Keywords
- chemo-resistance, neoadjuvant SBRT
- Medical subject headings
- Triple Negative Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
24 Gy in 3 daily fractions (8 Gy each) to the breast primary tumor, started within 1 week after confirmation of chemotherapy resistance.
Toripalimab (anti-PD-1 antibody)Drug
240 mg intravenous infusion every 21 days for 4 cycles
Chemotherapy switchDrug
Albumin-bound paclitaxel 125 mg/m² (days 1 \& 8) plus carboplatin AUC 6 (day 1)
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Radiation: SBRT; Drug: Toripalimab (anti-PD-1 antibody); Drug: Chemotherapy switch |
What is being measured
The primary outcome is the main question the study is designed to answer.
pCR rate
Pathological complete response (pCR), percentage of patients with no invasive residual tumor in breast and lymph nodes (ypT0/is ypN0) at surgery.
Measured: At definitive surgery, 3-5 weeks after completion of cycle 4 (week 15 from study entry)
Secondary outcomes (2)
ORR Rate
Proportion of patients achieving complete or partial tumor shrinkage by RECIST 1.1 on MRI.
Measured: After cycle 4, within 2 weeks before surgery (week 13).
Acute and late toxicities
Acute Radiation Skin Reaction;Immune-Related Adverse Events (irAEs)
Measured: From first SBRT fraction to 30 days post-SBRT (week 5); From first toripalimab dose to 90 days after last dose (week 28)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2026
- Study start4 Jan 2026
- Primary completion4 Jan 2028 (estimated)
- Study completion4 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for TNBC, Triple Negative Breast CancerStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07457359
- Sponsor's protocol ID
- Y2025-1398
- Acronym
- NEOTRIO-2
- Status last verified
- Dec 2025
- First submitted
- 4 Mar 2026
- Last updated
- 9 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Toripalimab Combined With Preoperative Radiotherapy for Initial Chemotherapy-Nonresponding Triple-Negative Breast Cancer Patients (NEOTRIO-2)
- ClinicalTrials.gov ID
- NCT07457359
- Acronym / sponsor ID
- NEOTRIO-2 / Y2025-1398
- Conditions
- TNBC, Triple Negative Breast Cancer
- Keywords
- chemo-resistance, neoadjuvant SBRT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 4 Jan 2026 (actual)
- Primary completion
- 4 Jan 2028 (estimated)
- Study completion
- 4 Jan 2029 (estimated)
- First posted
- 9 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SBRT-Toripalimab-Chemo Rescue | Experimental | Radiation: SBRT, Drug: Toripalimab (anti-PD-1 antibody), Drug: Chemotherapy switchAll 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SBRT24 Gy in 3 daily fractions (8 Gy each) to the breast primary tumor, started within 1 week after confirmation of chemotherapy resistance. | Radiation | SBRT-Toripalimab-Chemo Rescue |
| Toripalimab (anti-PD-1 antibody)240 mg intravenous infusion every 21 days for 4 cycles | Drug | SBRT-Toripalimab-Chemo Rescue |
| Chemotherapy switchAlbumin-bound paclitaxel 125 mg/m² (days 1 \& 8) plus carboplatin AUC 6 (day 1) | Drug | SBRT-Toripalimab-Chemo Rescue |
Primary outcome
pCR rate
Time frame: 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.
2 secondary outcomes
ORR Rate
Time frame: After cycle 4, within 2 weeks before surgery (week 13).
Acute and late toxicities
Time frame: From first SBRT fraction to 30 days post-SBRT (week 5); From first toripalimab dose to 90 days after last dose (week 28)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SBRT, Toripalimab (anti-PD-1 antibody) and Chemotherapy switch in people with TNBC, Triple Negative Breast Cancer, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 9 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ting Zhang, phD. (+86-571-87783521, zezht@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pCR rate (time frame: At definitive surgery, 3-5 weeks after completion of cycle 4 (week 15 from study entry)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2026.