Breast Cancer
Conditions
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.
Interventions
DRUGToripalimab
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.
RADIATIONSBRT
Local radiotherapy: Subjects received concurrent stereotactic body radiotherapy (SBRT，25 Gray in 5 fractions) for the primary lesion, within 5 weeks before the surgery.
DRUGstandard neoadjuvant chemotherapy regimens
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.
Sponsors
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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): 1. Absolute neutrophil count (ANC) ≥1.5×10⁹/L; 2. Platelet count ≥100×10⁹/L; 3. Hemoglobin ≥9 g/dL; 4. Serum albumin ≥3.0 g/dL; 5. Total bilirubin ≤1.5×upper limit of normal (ULN), alanine transaminase (ALT) and/or aspartate transaminase (AST) ≤2.5×ULN; 6. Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (calculated according to the Cockcroft-Gault formula); 7. International Normalized Ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×ULN (screening is permitted for patients receiving stable-dose anticoagulant therapy \[e.g., low-molecular-weight heparin or warfarin\] with INR within the expected therapeutic range for the anticoagulant). * Female subjects of childbearing potential must undergo a urine or serum pregnancy test within 72 hours prior to the first administration of the study drug with a negative result, and agree to use an effective contraceptive method during the trial and for 6 months after the last dose. Male subjects whose partners are women of childbearing potential must use an effective contraceptive method during the trial and for 6 months after the last dose.
Exclusion criteria
* 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: 1. Major surgery or severe trauma within 4 weeks prior to the first dose of study drug; 2. 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; 3. Previous vaccination with anti-tumor vaccine, or vaccination with live vaccine within 4 weeks prior to the first dose of study drug; 4. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pathologic complete response（pCR） | Up to12 months | 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. |
Contacts
CONTACTLina Zhang
Outcome results
None listed