Phase II Exploratory Study of Toripalimab Combined With SBRT in HER2-Negative Breast Cancer Patients With Insensitivity to Neoadjuvant Chemotherapy

NCT07410234 | Not Yet Recruiting Phase 2

• 1 other identifier: TJCIH-TNBCTori-2026
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to evaluate the efficacy and safety of toripalimab combined with radiochemotherapy as perioperative therapy in HER2-negative breast cancer patients insensitive to neoadjuvant chemotherapy. This was a multicohort, single-center exploratory clinical study. Eligible patients were initially administered standard neoadjuvant chemotherapy (TAC or TE regimen). Efficacy assessment was performed after 2 cycles of neoadjuvant chemotherapy, and only those evaluated as stable disease (SD) were formally enrolled. Enrolled patients were stratified into the HR-positive group and the triple-negative breast cancer (TNBC) group, with each group further divided into 3 arms receiving the following treatments respectively:

• Cohort 1: Continued the original neoadjuvant chemotherapy for 4 cycles, followed by surgical treatment within 5 weeks for eligible patients.
• Cohort 2: Received the original neoadjuvant chemotherapy regimen plus toripalimab for 4 cycles, followed by surgery within 5 weeks; toripalimab monotherapy was continued for an additional 13 cycles postoperatively.
• Cohort 3: Received the original neoadjuvant chemotherapy regimen plus toripalimab for 4 cycles combined with concurrent stereotactic body radiation therapy (SBRT, 25Gy/5f), followed by surgery within 5 weeks; toripalimab monotherapy was continued for an additional 13 cycles postoperatively.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response（pCR）

  pCR is defined as the absence of residual invasive cancer on resected breast specimen and the sampled regional lymph nodes as shown by hematoxylin-eosin staining after completion of the neoadjuvant treatment.

  Up to12 months

Study Arms (6)

HR1

OTHER

Drug: standard neoadjuvant chemotherapy regimens

HR2

EXPERIMENTAL

Drug: Toripalimab; Drug: standard neoadjuvant chemotherapy regimens

HR3

EXPERIMENTAL

Drug: Toripalimab; Radiation: SBRT; Drug: standard neoadjuvant chemotherapy regimens

TNBC1

OTHER

Drug: standard neoadjuvant chemotherapy regimens

TNBC2

EXPERIMENTAL

Drug: Toripalimab; Drug: standard neoadjuvant chemotherapy regimens

TNBC3

EXPERIMENTAL

Drug: Toripalimab; Radiation: SBRT; Drug: standard neoadjuvant chemotherapy regimens

Interventions

Toripalimab DRUG

Preoperative: toripalimab, 240mg, IV, D1, Q3W. Preoperative toripalimab contains 4 cycles. Postoperative: Toripalimab 240mg, IV, D1, Q3W. . Postoperative Toripalimab following surgery within 5 weeks for 13 cycles.

HR2; HR3; TNBC2; TNBC3

SBRT RADIATION

Local radiotherapy: Subjects received concurrent stereotactic body radiotherapy (SBRT，25 Gray in 5 fractions) for the primary lesion, within 5 weeks before the surgery.

HR3; TNBC3

standard neoadjuvant chemotherapy regimens DRUG

standard neoadjuvant chemotherapy regimens for breast cancer: TAC, TE, etc. T: docetaxel, nab-paclitaxel or paclitaxel. Routine clinical dosage and administration shall be adopted. A: epirubicin, pirarubicin or doxorubicin. Routine clinical dosage and administration shall be adopted. C: cyclophosphamide 500 mg/m², IV. Q3W. Dose reduction and treatment delay are permitted; the maximum allowable delay is 3 weeks, calculated from the last administration date. Treatment shall be discontinued if this limit is exceeded. E: epirubicin. Routine clinical dosage and administration shall be adopted.

HR1; HR2; HR3; TNBC1; TNBC2; TNBC3

Eligibility Criteria

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

You may qualify if:

• The patient voluntarily participates in this study, has signed the informed consent form, with good compliance and willingness to cooperate with follow-up.
• Aged ≥18 years, male or female.
• Histologically confirmed unilateral primary invasive breast cancer, meeting the criteria of cT2-4N0-2M0.
• HER-2 expression negative by immunohistochemistry (IHC); for patients with HER-2 2+ expression, HER-2 gene non-amplification must be confirmed by in situ hybridization (ISH).
• Patients with stable disease (SD) assessed after 2 cycles of neoadjuvant chemotherapy.
• At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).
• Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1.
• Expected survival ≥3 months.
• At least one tumor tissue biopsy specimen of the primary tumor obtained during screening must be provided to the central laboratory.
• Function of vital organs meets the following requirements (administration of any blood components or cell growth factors is not allowed within 2 weeks before the start of screening tests):
• Absolute neutrophil count (ANC) ≥1.5×10⁹/L;
• Platelet count ≥100×10⁹/L;
• Hemoglobin ≥9 g/dL;
• Serum albumin ≥3.0 g/dL;
• Total bilirubin ≤1.5×upper limit of normal (ULN), alanine transaminase (ALT) and/or aspartate transaminase (AST) ≤2.5×ULN;

You may not qualify if:

• A history of invasive malignancy within 5 years prior to signing the informed consent form, except for adequately treated basal/squamous cell skin cancer or carcinoma in situ of the cervix.
• Receipt of any of the following treatments:
• Major surgery or severe trauma within 4 weeks prior to the first dose of study drug;
• Receipt of any non-neoadjuvant anti-tumor therapy (including chemotherapy, radiotherapy, immunotherapy, targeted therapy, biotherapy, or tumor embolization) within 12 months prior to the first dose of study drug;
• Previous vaccination with anti-tumor vaccine, or vaccination with live vaccine within 4 weeks prior to the first dose of study drug;
• Requirement for systemic therapy with corticosteroids (\>10 mg prednisone equivalent per day) or other immunosuppressants within 2 weeks prior to the first dose of study drug.
• A current or historical diagnosis of any active autoimmune disease (e.g., interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism); excluding vitiligo, or patients with childhood asthma/allergies that have resolved and require no intervention in adulthood. Patients with autoimmune-mediated hypothyroidism on a stable dose of thyroid replacement hormone and patients with type 1 diabetes on a stable dose of insulin are eligible for enrollment.
• A history of immunodeficiency, including positive HIV test results, other acquired/congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.
• Uncontrolled clinical cardiac symptoms or diseases, including: (1) heart failure of NYHA Class Ⅱ or higher; (2) unstable angina pectoris; (3) myocardial infarction within 1 year; (4) clinically significant supraventricular/ventricular arrhythmias requiring clinical intervention.
• Severe infection (CTCAE Grade \>2) within 4 weeks prior to the first dose of study drug (e.g., severe pneumonia, bacteremia, infectious complications requiring hospitalization); active pulmonary inflammation indicated by baseline chest imaging; signs and symptoms of infection requiring oral/intravenous antibiotic therapy within 2 weeks prior to the first dose of study drug (prophylactic antibiotic use is excluded); active pulmonary tuberculosis confirmed by medical history or CT scan, a history of active pulmonary tuberculosis within 1 year prior to enrollment, or a history of active pulmonary tuberculosis more than 1 year prior to enrollment without standard treatment.
• Active hepatitis B (HBV DNA ≥ 2000 IU/mL or 10⁴ copies/mL) or active hepatitis C (positive anti-HCV antibodies with HCV-RNA above the lower limit of detection of the assay).
• Known hypersensitivity or intolerance to toripalimab, chemotherapy drugs used in the study, or their excipients.
• Pregnant or lactating women; subjects of childbearing potential who are unwilling or unable to adopt effective contraceptive measures.
• Current participation in another clinical study or participation within the previous 4 weeks.
• Any other condition that, in the investigator's judgment, makes the subject unsuitable for participation in the study.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

toripalimab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Lina Zhang

CONTACT

86-22-23359337; linazhang2005@126.com

Study Design

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

Study Record Dates

• First Submitted: February 8, 2026
• First Posted: February 13, 2026
• Study Start: February 21, 2026
• Primary Completion (Estimated): February 21, 2028
• Study Completion (Estimated): February 21, 2029
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share