Clinical trial NCT06927180: SHR-A1811 Plus Pertuzumab in the Neoadjuvant Treatment of HER2 Positive BC
Official title: SHR-A1811 Plus Pertuzumab in Combination With or Without Albumin-paclitaxel as Neoadjuvant Treatment for Early or Locally Advanced HER2-positive Breast Cancer：A Prospective, Randomized, Open-label, Phase II Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3)
Keywords: Breast Cancer
HER2-positive Breast Cancer
pathologic complete response
SHR-A1811
Pertuzumab
Albumin-Paclitaxel
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2025-04-15
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Patients who meet the inclusion criteria were randomly divided into SHR-A1811+pertuzumab and SHR-A1811+pertuzumab+albumin-paclitaxel and TCbHP group in a 1:1:1 ratio.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to evaluate the efficacy and safety of SHR-A1811 plus pertuzumab in combination with or without albumin-paclitaxel neoadjuvant therapy for early or locally advanced HER2-positive breast cancer. The main questions it aims to answer are:

* Does the pCR of SHR-A1811 plus pertuzumab with or without albumin-paclitaxel improve compared to the current standard of treatment?
* Is the safety of SHR-A1811 plus pertuzumab with or without albumin-paclitaxel better compared to the current standard of treatment? Researchers will compare SHR-A1811+pertuzumab or SHR-A1811+pertuzumab+albumin-paclitaxel to TCbHP to see if SHR-A1811 plus pertuzumab with or without albumin-paclitaxel works to treat early or locally advanced HER2-positive breast cancer.

Subjects will be randomly assigned 1:1:1 to：

* cohort 1：SHR-A1811 combined with pertuzumab for 6 cycles;
* cohort 2：SHR-A1811 combined with pertuzumab and albumin-paclitaxel for 6 cycles;
* cohort 3：TCbHP (docetaxel, carboplatin, trastuzumab and pertuzumab) for 6 cycles.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, questionnaires, and scans.


Eligibility criteria: Inclusion Criteria:

* Age: 18-70 years old, ECOG 0-1 point.
* Clinical T2-T4, with any LN, M0.
* HER2+, invasive breast cancer confirmed by histopathology;(HER2 positive expression means that there is at least one case of tumor cell immunohistochemical staining intensity of 3+or positive confirmed by fluorescence in situ hybridization \[FISH\] in the pathological test/review of the primary focus conducted by the Pathology Department of the Research Center Hospital).
* Having clinically measurable lesions: measurable lesions displayed on ultrasound, mammography, or MR (optional) within the first month of randomization.
* Organ and bone marrow function tests within one month before chemotherapy indicate no contraindications to chemotherapy：Absolute value of neutrophil count ≥ 1.5 × 10\^9/L; Hemoglobin ≥ 90g/L; Platelet count ≥ 100 × 10\^9/L; Total bilirubin≤1.5 ULN (upper limit of normal value); Creatinine≤1.5 × ULN; AST/ALT ≤ 2.5 × ULN.
* Cardiac ultrasound: Left ventricular ejection fraction (LVEF ≥ 50%).
* Women of childbearing age tested negative for serum pregnancy test 7 days before randomization.
* Sign an informed consent form.

Exclusion Criteria:

* Stage IV (metastatic) breast cancer.
* Has received chemotherapy, endocrine therapy, targeted therapy, reflex therapy, etc. for this disease.
* The patient has a second primary malignant tumor, except for fully treated skin cancer.
* The patient had undergone major surgical procedures unrelated to breast cancer within 4 weeks before enrollment, or the patient has not fully recovered from such surgical procedures.
* The presence of uncontrolled cardiovascular and cerebrovascular disease, including (but not limited to) any of the following within the 6 months prior to the first dose: congestive heart failure (NYHA III or IV), myocardial infarction or cerebral infarction, pulmonary embolism, unstable angina, or arrhythmia requiring treatment at the time of screening; Primary cardiomyopathy (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restricted cardiomyopathy, undefined cardiomyopathy); A clinically significant history of prolonged QTc, grade II type II atrioventricular block or grade III atrioventricular block or QTc interphase (F method) \> 470 msec (female); Atrial fibrillation (EHRA grade ≥2b); Unmanageable hypertension, which the investigators judged unsuitable for study participation.
* Due to serious and uncontrollable other medical diseases, researchers believe that there are contraindications to chemotherapy.
* Individuals with a known history of allergies to the drug components of this protocol;
* Having a history of immunodeficiency, including HIV testing positive, or suffering from other acquired or congenital immunodeficiency diseases, or having a history of organ transplantation.

Primary outcomes:
measure: Pathological complete response rate (pCR rate)
timeFrame: After surgery（within 1 month）
Secondary outcomes:
measure: Invasive Disease Free Survival of 5 years
timeFrame: 5-year
measure: Event-Free Survival of 5 years
timeFrame: 5-year
measure: Objective Response Rate (ORR)
timeFrame: During neoadjuvant therapy before surgery（within 6 months）
measure: Adverse Events rate
timeFrame: 2-year
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Zhenzhen Liu
role: PRINCIPAL_INVESTIGATOR
References: