SHR-A1811 Plus Pertuzumab in the Neoadjuvant Treatment of HER2 Positive BC

Phase 2

Not yet recruiting

• Conditions: Breast Cancer Early Stage Breast Cancer (Stage 1-3)
• Interventions: Drug: SHR-A1811; Drug: Pertuzumab; Drug: Docetaxel; Drug: Carboplatin; Drug: Albumin-Paclitaxel; Drug: Trastuzumab

• Registration Number: NCT06927180
• Lead Sponsor: Henan Cancer Hospital

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-04
• Status Verified: 2025-04
• Study First Submitted QC: 2025-04-13
• Last Update Submitted: 2025-04-13
• Study First Posted: 2025-04-15
• Last Update Posted: 2025-04-15
• Study Start: 2025-04-16
• Primary Completion: 2029-05-01
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: Female
• Target Recruitment: 180

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1：SHR-A1811+Pertuzumab	SHR-A1811	Participants will receive SHR-A1811+Pertuzumab for 6 cycles.
Cohort 1：SHR-A1811+Pertuzumab	Pertuzumab	Participants will receive SHR-A1811+Pertuzumab for 6 cycles.
Cohort 3：TCbHP	Docetaxel	Participants will receive Docetaxel +Carboplatin +Trastuzumab +Pertuzumab for 6 cycles.
Cohort 3：TCbHP	Carboplatin	Participants will receive Docetaxel +Carboplatin +Trastuzumab +Pertuzumab for 6 cycles.
Cohort 2：SHR-A1811+Pertuzumab+Albumin-Paclitaxel	SHR-A1811	Participants will receive SHR-A1811+Pertuzumab+Albumin-Paclitaxel for 6 cycles.
Cohort 2：SHR-A1811+Pertuzumab+Albumin-Paclitaxel	Pertuzumab	Participants will receive SHR-A1811+Pertuzumab+Albumin-Paclitaxel for 6 cycles.
Cohort 2：SHR-A1811+Pertuzumab+Albumin-Paclitaxel	Albumin-Paclitaxel	Participants will receive SHR-A1811+Pertuzumab+Albumin-Paclitaxel for 6 cycles.
Cohort 3：TCbHP	Pertuzumab	Participants will receive Docetaxel +Carboplatin +Trastuzumab +Pertuzumab for 6 cycles.
Cohort 3：TCbHP	Trastuzumab	Participants will receive Docetaxel +Carboplatin +Trastuzumab +Pertuzumab for 6 cycles.

Primary Outcome Measures

Name	Time	Method
Pathological complete response rate (pCR rate)	After surgery（within 1 month）	After neoadjuvant chemotherapy and surgery, the resected specimen (breast + axilla) was free of any invasive cancer (ie, ypT0/is, ypN0)

Secondary Outcome Measures

Name	Time	Method
Invasive Disease Free Survival of 5 years	5-year	5-year Invasive Disease-Free Survival was defined as patients who did not experience regional, contralateral or distant recurrence, or dies during a follow-up period of at least 5 years from the date of surgery.
Event-Free Survival of 5 years	5-year	5-year Event-Free Survival was defined as patients who did not experience disease progression during neoadjuvant therapy, local or distant recurrence, second primary malignancy (breast or other cancer), or dies during a follow-up period of at least 5 years after treatment.
Objective Response Rate (ORR)	During neoadjuvant therapy before surgery（within 6 months）	ORR is the proportion of patients whose tumors have shrunk significantly over the course of treatment. Specifically, ORR includes both partial response (PR) and complete response (CR). Partial response (PR) : The maximum diameter or volume of the tumor is reduced by at least 30%, but it does not completely disappear. Complete response (CR) : The tumor disappears completely and no visible signs of cancer are confirmed by imaging tests, such as CT scans, MRI, or ultrasound.
Adverse Events rate	2-year	Evaluate the nature, incidence and severity of chemotherapy adverse events according to CTCAE 5.0

Trial Locations

Locations (1)

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China