A Prospective, Open-label, Randomized Trial Comparing Switch to A1811 Versus Continued THP Neoadjuvant Therapy After THP Induction in HER2-Positive Breast Cancer (SwithADC)
Switching to A1811 vs. Continuation of the Original Neoadjuvant Regimen After THP Induction in HER2-Positive Breast Cancer
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).
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: swithing to A1811
Switch to A1811 therapy for 4 cycles |
Switch to A1811 therapy for 4 cycles |
|
Active Comparator: THP
Continue the THP regimen for 4 cycles |
Continue the THP regimen for 4 cycles |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
pCR
Time Frame: 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. |
From enrollment to the end of treatment at 6 months
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
ORR
Time Frame: 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. |
From enrollment to the end of treatment at 6 months
|
|
EFS
Time Frame: 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. |
From enrollment to the end of treatment at 5 years
|
|
OS
Time Frame: From enrollment to the end of treatment at 5 years
|
he time from randomization to death from any cause. |
From enrollment to the end of treatment at 5 years
|
|
AE rate
Time Frame: 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. |
From enrollment to the end of treatment at 4 weeks
|
|
RCB0/1
Time Frame: 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 |
From enrollment to the end of treatment at 4 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MA-BC-II-154
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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