Neoadjuvant Trastuzumab-rezetecan Plus Pertuzumab or Nab-Paclitaxel, Carboplatin, Trastuzumab, and Pyrotinib After Suboptimal Response to Neoadjuvant Dual HER2-Targeted Therapy Combined With Chemotherapy in HER2-Positive Early Breast Cancer

NCT07340398 | Recruiting Phase 2

• 1 other identifier: 2025-1587
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, response-guided phase II study investigates individualized neoadjuvant treatment strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. After receiving neoadjuvant dual-HER2-targeted therapy with chemotherapy, patients are evaluated for their treatment response. Those achieving an adequate response continue the therapy, whereas patients with a suboptimal response transition to an intensified investigational regimen incorporating novel targeted agents. This adaptive approach aims to optimize pathologic response, minimize unnecessary toxicity, and explore more effective treatment options for individuals with insufficient benefit from conventional neoadjuvant therapy.

Conditions

HER2-positive Early Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Total Pathological Complete Response (tpCR) Rate: ypT0/Tis, ypN0

  The tpCR rate is defined as the proportion of participants with no residual invasive cancer cells in both the breast primary tumor site (residual in situ cancer cells are permitted) and all sampled axillary lymph nodes.

  18 weeks

Secondary Outcomes (4)

• Breast Pathological Complete Response (bpCR) Rate: ypT0/Tis

  18 weeks

• Objective Response Rate (ORR)

  18 weeks

• Event-Free Survival (EFS)

  Approximately five years

• Adverse Event (AE)

  Approximately three years

Study Arms (2)

nab-PCbHPy

EXPERIMENTAL

Drug: Nab paclitaxel; Drug: Carboplatin; Drug: Trastuzumab; Drug: Pyrotinib

SHR-A1811+P

EXPERIMENTAL

Drug: Pertuzumab; Drug: SHR-A1811

Interventions

Nab paclitaxel DRUG

Nab paclitaxel

nab-PCbHPy

Carboplatin DRUG

carboplatin

nab-PCbHPy

Trastuzumab DRUG

trastuzumab

nab-PCbHPy

Pertuzumab DRUG

pertuzumab

SHR-A1811+P

SHR-A1811 DRUG

a HER2-targeted antibody-drug conjugate (ADC)

Also known as: Trastuzumab-rezetecan

SHR-A1811+P

Pyrotinib DRUG

Pyrotinib: an oral irreversible pan-HER tyrosine kinase inhibitor (TKI).

nab-PCbHPy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 and ≤75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Primary tumor size \>1 cm.
• Histologically confirmed invasive breast cancer, clinically staged as:
• Stage I (T1cN0M0)
• Stage II (T1cN1M0, T2N0-1M0 or T3N0M0)
• Stage III (T2N2-3M0, T3N1-3M0, or T4N0-3M0)
• HER2-positive status: IHC 3+ or IHC 2+ with positive ISH.
• Adequate major organ function:
• Hematology (no transfusion or hematopoietic growth factors, e.g., G-CSF, within 14 days):
• Hemoglobin ≥100 g/L
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
• Platelet count ≥100 × 10⁹/L
• Biochemistry:
• Total bilirubin ≤1.5 × ULN

You may not qualify if:

• Prior anti-tumor therapy for breast cancer, including chemotherapy, radiotherapy, targeted therapy, or endocrine therapy.
• Concurrent administration of any other anti-tumor treatment.
• Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer.
• Breast cancer not confirmed histologically.
• History of other malignancy within the past 5 years, except successfully treated cervical carcinoma in situ.
• Severe dysfunction of major organs (heart, liver, kidney).
• Conditions affecting oral drug administration or absorption, e.g., inability to swallow, chronic diarrhea, or intestinal obstruction.
• Participation in another investigational drug trial within 4 weeks prior to enrollment.
• Known hypersensitivity to study drug components; history of immunodeficiency (HIV positive, active HCV, active hepatitis B, other congenital/acquired immunodeficiency) or prior organ transplantation.
• History of clinically significant cardiac disease, including:
• Arrhythmia requiring medication
• Myocardial infarction
• Heart failure
• Other cardiac conditions deemed unsuitable for study participation by the investigator
• Pregnant or breastfeeding women, or women of childbearing potential who test positive at baseline or are unwilling to use effective contraception throughout the study.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, China

RECRUITING

MeSH Terms

Interventions

Taxes; Carboplatin; Trastuzumab; pertuzumab; pyrotinib

Intervention Hierarchy (Ancestors)

Economics; Health Care Economics and Organizations; Coordination Complexes; Organic Chemicals; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yiding Chen

CONTACT

15868131018; ydchen@zju.edu.cn

Yunxiang Zhou

CONTACT

yxzhou@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 14, 2026
• Study Start: December 25, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): January 1, 2031
• Last Updated: January 21, 2026

Record last verified: 2025-12

Locations

CN (1)