Breast Cancer (Early Breast Cancer)
Conditions
Brief summary
This is a multicenter, open-label, randomized controlled trial. A total of 432 eligible patients with HER2-positive breast cancer will be enrolled after screening. All patients will receive THP-based neoadjuvant therapy (THP) for 2 cycles. After 2 cycles, imaging-based response will be assessed according to RECIST v1.1. Patients with a response or stable disease (PR or SD) will be randomized 1:1 into the experimental group or the control group. Randomization occurs after the 2-cycle assessment. Experimental group: Switch to A1811 therapy for 4 cycles. Control group: Continue the THP regimen for 4 cycles. After completing a total of 6 cycles of neoadjuvant therapy, all patients will undergo definitive surgical treatment for pathological assessment. Primary endpoint: Pathologic complete response (pCR).
Interventions
DRUGA1811
Switch to A1811 therapy for 4 cycles
DRUGTHP
Continue the THP regimen for 4 cycles
Sponsors
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
\- 1.18-75 years old 2.Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 3.HER2-positive breast cancer was defined by core needle biopsy pathology showing HER2 positivity, with IHC score of 3+ or IHC score 2+ with positive ISH results 4.At initial diagnosis, tumors were stage II-III according to the AJCC 8th edition breast cancer staging system and deemed operable 5.no prior history of any systemic anti-cancer therapy for breast cancer 6.Adequate organ function 7.Women of reproductive potential must have a negative pregnancy test prior to enrollment. Women of childbearing potential must commit to using effective contraception from study start until 6 months after the last dose of study medication, with ongoing assessment of adherence to contraception. 8.All participants must voluntarily participate in this study and provide written informed consent, with consent approved by the ethics committee prior to use
Exclusion criteria
\- 1.Bilateral breast cancer, stage IV breast cancer, or inflammatory breast cancer; 2.Any history of malignancy within 5 years prior to signing informed consent, excluding treated cervical carcinoma in situ, non-melanoma skin cancer (basal cell carcinoma or squamous cell carcinoma) in remission; 3.Receiving anti-tumor therapy in another interventional clinical trial concurrently, including but not limited to chemotherapy, endocrine therapy, biologic therapy, bone-modifying agents, or immune checkpoint inhibitors; 4.Major surgery unrelated to breast cancer within 4 weeks prior to the first dose of study drug, or not yet fully recovered from such surgery; 5.Severe cardiac disease or unstable condition; 6.Uncontrolled active infections; history of immunodeficiency, including HIV-positive status, or other acquired or congenital immunodeficiency diseases, or a history of organ transplantation 7. Known hypersensitivity to any component of the study drug regimen; 8. Pregnant or breastfeeding women, women of reproductive potential with a positive baseline pregnancy test, or sexually active individuals not willing to use effective contraception from the time of enrollment through 6 months after the last study drug administration; 9.Known or suspected interstitial pneumonia; major or clinically significant pre-existing respiratory diseases within 3 months prior to first dose that could interfere with assessment of drug-related pulmonary toxicity or its management. 10.urrently participating in another interventional pharmacologic clinical study; 11. Refusal to comply with follow-up procedures; 12. Presence of other serious medical or psychiatric conditions or laboratory abnormalities that may increase the risk of participation, interfere with study results, or for any other reason lead the investigator to believe the subject is not suitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pCR | From enrollment to the end of treatment at 6 months | After completion of neoadjuvant therapy, patients underwent definitive surgical resection; histopathological assessment of the hematoxylin and eosin-stained excised breast cancer specimens and all ipsilateral lymph node samples showed no residual invasive cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR | From enrollment to the end of treatment at 6 months | The proportion of subjects achieving CR or PR as the best tumor response during neoadjuvant therapy. The investigators will assess objective response rate (ORR) according to RECIST v1.1. |
| EFS | From enrollment to the end of treatment at 5 years | Time from randomization to the first occurrence of any of the following events: disease progression prior to surgery, local or distant recurrence after surgery, or death from any cause. |
| OS | From enrollment to the end of treatment at 5 years | he time from randomization to death from any cause. |
| AE rate | From enrollment to the end of treatment at 4 weeks | AEs were graded according to NCI-CTCAE v5.0. Descriptive statistics were summarized by treatment group for: any AE, AEs ≥ Grade 3, SAEs, drug-related AEs, drug-related SAEs, AEs leading to dose modification, and AEs leading to discontinuation of therapy. For each category, the number of patients with at least one event and the proportion (with 95% CI) of the corresponding total evaluable patients in each group were reported. |
| RCB0/1 | From enrollment to the end of treatment at 4 weeks | Residual Cancer Burden (RCB) was calculated from the surgical specimen using the published MD Anderson RCB methodology, incorporating: (1) residual tumor bed size in the breast (cm), (2) invasive cancer cellularity (%), (3) in situ component (%), (4) number of positive axillary lymph nodes and the largest metastasis size (mm). The resulting continuous RCB index (0-11.9) was categorized into RCB classes (RCB I, II, III) according to established cutoffs. Calculations were performed using the MD Anderson RCB calculator or an equivalent validated implementation, with results reviewed by study pathologists |
Outcome results
None listed