Artificial Intelligence Model-Guided Neoadjuvant Anti-HER2 Targeted Therapy

Artificial Intelligence Model-Guided Neoadjuvant Anti-HER2 Targeted Therapy: A Randomized, Controlled, Open-Label, Multicenter Phase III Clinical Study

Based on total pathologic complete response (tpCR) after surgery, to evaluate the efficacy of an artificial intelligence model-matched anti-HER2 targeted treatment strategy (investigational arm) versus nab-paclitaxel + carboplatin + trastuzumab + pertuzumab (PCbHP, control arm) as neoadjuvant therapy for patients with early or locally advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: SHR- A1811; Drug: PCbHP; Drug: SHR- A1811+ Pyrotinib

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zhimin Shao, MD.PhD; Phone Number: 18017312288; Email: zhimingshao@yahoo.com

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Zhimin Shao, MD.PhD; Phone Number: 18017312288; Email: zhimingshao@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Female patients aged 18 to 75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Histologically confirmed unilateral primary invasive breast cancer, staged as at least cT2 or cN1 (i.e., AJCC 8th edition stage II-III), and M0.
• Pathologically confirmed HER2-positive breast cancer, defined as HER2 IHC 3+, or IHC 2+ with positive in situ hybridization (ISH).
• At least one measurable lesion according to RECIST version 1.1.
• Adequate major organ function, meeting all of the following criteria: Hematology criteria (without blood transfusion or hematopoietic growth factor support within 7 days before screening): hemoglobin (HB) >= 90 g/L; absolute neutrophil count (ANC) >= 1.5 x 10^9/L; platelet count (PLT) >= 75 x 10^9/L.
• Biochemistry criteria: total bilirubin (TBIL) <= 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <= 3 x ULN; serum creatinine (Cr) <= 1.5 x ULN; endogenous creatinine clearance > 50 mL/min (Cockcroft-Gault formula).
• 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) < 470 msec; echocardiography: left ventricular ejection fraction (LVEF) >= 55%.
• Women of childbearing potential must use at least one medically accepted contraceptive method during study treatment and for at least 3 months after the last dose of study drug.
• Subjects must voluntarily participate in the study, sign the informed consent form, demonstrate good compliance, and cooperate with follow-up.

Exclusion Criteria:

• Bilateral breast cancer, inflammatory breast cancer, or clinically stage IV (metastatic) breast cancer.
• Any prior systemic targeted therapy, chemotherapy, endocrine therapy, biologic therapy, radiotherapy, or immunotherapy for any reason.
• Any of the following comorbidities, medical histories, or treatment histories:
• Known or suspected interstitial pneumonitis; or moderate to severe pulmonary disease severely affecting respiratory function, such as severe asthma or severe chronic obstructive pulmonary disease (COPD).
• Serious cardiovascular or cerebrovascular disease, including but not limited to New York Heart Association (NYHA) class II or higher heart failure (including class II), myocardial infarction or cerebrovascular accident (including cerebral ischemia or symptomatic cerebral infarction) within 3 months before first dosing, or persistent arrhythmia of grade >= 2.
• Severe systemic infection (e.g., requiring intravenous antibiotics, antifungal agents, or antiviral drugs according to clinical practice standards), or unexplained fever > 38.5 degrees C during screening or before first dosing.
• Clinically significant bleeding symptoms within 1 month before signing informed consent, or definite bleeding tendency, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or baseline fecal occult blood of ++ or above.
• Known hypersensitivity or intolerance to the investigational medicinal products or their excipients.
• Any other malignancy within the previous 5 years, except cured cervical carcinoma in situ or non-melanoma skin cancer.
• Pregnancy or lactation, or refusal by women of childbearing potential to use appropriate contraception during the trial.
• Participation in another clinical trial within 30 days before the first dose of study drug.
• Any other condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: experimental group	Drug: SHR- A1811; the experimental group consists of different neoadjuvant treatment regimens matched by the artificial intelligence model; Drug: PCbHP; Standard neoadjuvant treatment regimen for HER2-positive breast cancer; Drug: SHR- A1811+ Pyrotinib; the investigational arm consists of different neoadjuvant treatment regimens matched by the artificial intelligence model
Active Comparator: control group	Drug: PCbHP; Standard neoadjuvant treatment regimen for HER2-positive breast cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pathologic Complete Response (pCR)	pCR is defined as the absence of noninvasive tumor residuals in breast and axillary lymph nodes (ypT0/is ypN0) after neoadjuvant therapy.	through study completion, up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR is defined as the proportion of patients who achieved a complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	up to 24 weeks

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: March 29, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; HER2-positive; early
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: SCHBCC-N0114

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No