Breast Cancer, HER2-positive Breast Cancer, Early-stage Breast Cancer, Locally Advanced Breast Cancer
Conditions
Brief summary
This is a prospective, multi-center, single-arm, phase 2 exploratory study to evaluate the efficacy and safety of adding 4 cycles of Trastuzumab Rezetecan (T-DXh), an anti-HER2 antibody-drug conjugate, as continued neoadjuvant therapy in patients with early or locally advanced HER2-positive breast cancer who have residual invasive disease after standard 6-cycle TCbHP (taxane, carboplatin, trastuzumab, pertuzumab) neoadjuvant therapy. Patients will receive 4 cycles of T-DXh (4.8 mg/kg IV Q3W) followed by radical surgery. The primary endpoint is tpCR rate. Secondary endpoints include ORR, EFS, OS, 3-year iDFS, and safety. Simon's two-stage design (H0: pCR ≤10%, H1: pCR ≥25%, α=0.05, β=0.2) requires 43 evaluable patients; with 10% dropout, 48 patients will be enrolled.
Interventions
An anti-HER2 antibody-drug conjugate (ADC) consisting of a humanized HER2-targeting monoclonal antibody (trastuzumab) conjugated to a DNA topoisomerase I inhibitor (SHR169265) via a cleavable tetrapeptide linker.
Sponsors
The First Affiliated Hospital with Nanjing Medical University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years. * For premenopausal and perimenopausal patients: negative pregnancy test and agreement to use reliable contraception during the treatment period. * Pathologically confirmed HER2-positive invasive breast cancer (IHC 3+ or IHC 2+ with FISH+). * Completed standard neoadjuvant TCbHP (taxane + carboplatin + trastuzumab + pertuzumab) with imaging assessment not achieving clinical complete remission (non-cCR). * Agree to undergo a core needle biopsy. * ECOG performance status 0 or 1. * Adequate organ function meeting the following criteria: hemoglobin ≥ 90 g/L, white blood cell count ≥ 3.5 × 10\^9/L, platelet count ≥ 100 × 10\^9/L, absolute neutrophil count ≥ 1.5 × 10\^9/L, AST/ALT ≤ 3 × ULN, total bilirubin ≤ 1.5 × ULN, serum creatinine ≤ 1.5 × ULN. * No myocardial ischemia on ECG; New York Heart Association (NYHA) functional class I; left ventricular ejection fraction (LVEF) ≥ 55% by echocardiography; cardiac troponin I (cTnI) and brain natriuretic peptide (BNP) within normal limits. * Signed informed consent.
Exclusion criteria
* Male breast cancer or inflammatory breast cancer. * Metastatic breast cancer (Stage IV). * Concurrent other malignancy or history of other malignancy within the past 5 years, except adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix. * Concurrent other anti-tumor therapy or participation in another clinical trial. * Severe non-malignant disease that would affect compliance or place the patient at risk. * Major surgery within 4 weeks prior to start of study treatment or anticipated need for major surgery during the study. History of allergic reaction or contraindication to any component of the study drug. * Dementia, mental abnormality, or any psychiatric illness that interferes with understanding of the informed consent. * Any other condition assessed by the investigator as unsuitable for inclusion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Total Pathological Complete Response (tpCR) | At the time of surgery, approximately 12 weeks after the start of the 4-cycle Trastuzumab Rezetecan treatment. | Absence of invasive residual cancer in both the breast primary tumor and axillary lymph nodes (ypT0/is, ypN0) after neoadjuvant therapy and surgery. Presence of ductal carcinoma in situ (DCIS) is allowed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 3-Year Invasive Disease-Free Survival (iDFS) Rate | 3 years after surgery. | Percentage of patients who are free from invasive disease at 3 years after surgery. Invasive disease events include ipsilateral invasive breast tumor recurrence, local/regional invasive recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, or death from any cause. |
| Incidence of Adverse Events (AEs) | From signing of informed consent until 28 days after the last dose of study treatment. | Number of participants experiencing adverse events. AEs are graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0. |
| Event-Free Survival (EFS) | From first dose up to 5 years after last patient enrolled. | Time from first dose of study treatment to the earliest occurrence of any of the following: disease progression (per RECIST 1.1), local/regional/distant recurrence, second primary tumor (breast or other), or death from any cause. |
| Overall Survival (OS) | From first dose up to 5 years after last patient enrolled. | Time from first dose of study treatment to death from any cause. |
Contacts
CONTACTXiaoan Liu
Outcome results
None listed