Adjuvant Trastuzumab Plus Neratinib in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer After Neoadjuvant Trastuzumab Plus Pertuzumab

NCT05760612 | Recruiting Phase 3

• 1 other identifier: SYSKY-2023-075-03
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

Neratinib is an irreversible pan-HER tyrosine kinase inhibitor (TKI). Currently, no studies have investigated the use of macromolecular anti-HER2 agents combined with TKIs for the treatment of non-pCR HER2-positive breast cancer following neoadjuvant therapy. Furthermore, there are no prospective randomized controlled trials comparing trastuzumab plus pertuzumab versus trastuzumab plus TKIs in HER2-positive breast cancer patients with residual cancer burden class (RCB) I or II after neoadjuvant trastuzumab and pertuzumab. Therefore, this study aimed to evaluate the efficacy and safety of adjuvant trastuzumab plus neratinib in patients with hormone receptor-positive/HER2-positive breast cancer and RCB 0/I following neoadjuvant trastuzumab and pertuzumab therapy.

Conditions

Early-stage Breast Cancer; HER2-positive Breast Cancer; Adjuvant Treatment After Trastuzumab; RCB Classification 1-2; Neratini

Keywords

Hormone receptor positive HER2 positive breast cancer; targeted therapy; adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Invasive disease free survival, IDFS

  The time from random assignment until the first occurrence of invasive disease recurrence, distant recurrence, or death from any cause.

  During the 3 years after random assignment

Secondary Outcomes (4)

• Disease free survival, DFS

  During the 3 years after random assignment

• Overall survival, OS

  During the 3 years after random assignment

• Distant disease free survival, DDFS

  During the 3 years after random assignment

• Incidence and severity of adverse events

  From signing the informed consent form until 28 days after completion of adjuvant treatment

Study Arms (2)

Trastuzumab combined with Pertuzumab

ACTIVE COMPARATOR

Trastuzumab (8 mg/kg IV loading dose, followed by 6 mg/kg IV once every 3 weeks), and pertuzumab (840 mg IV loading dose, followed by 420 mg IV once every 3 weeks). This regimen will be repeated for a total of 18 cycles,encompassing both the preoperative and adjuvant phases.

Drug: Trastuzumab and Pertuzumab

Trastuzumab combined with neratinib

EXPERIMENTAL

Trastuzumab (8 mg/kg IV loading dose, followed by 6 mg/kg IV once every 3 weeks), and neratinib 240 mg orally once daily. The trastuzumab treatment will be continued for a total of 18 cycles, encompassing both the preoperative and adjuvant phases, while neratinib will be maintained throughout the adjuvant period.

Drug: Trastuzumab and neratinib

Interventions

Trastuzumab and neratinib DRUG

Trastuzumab (8 mg/kg IV loading dose, followed by 6 mg/kg IV once every 3 weeks), and neratinib 240 mg orally once daily. The trastuzumab treatment will be continued for a total of 18 cycles, encompassing both the preoperative and adjuvant phases, while neratinib will be maintained throughout the adjuvant period.

Trastuzumab combined with neratinib

Trastuzumab and Pertuzumab DRUG

Trastuzumab (8 mg/kg IV loading dose, followed by 6 mg/kg IV once every 3 weeks), and pertuzumab (840 mg IV loading dose, followed by 420 mg IV once every 3 weeks). This regimen will be repeated for a total of 18 cycles,encompassing both the preoperative and adjuvant phases.

Trastuzumab combined with Pertuzumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients aged 18-70 years;
• Eastern Cooperative Oncology Group performance status of 0 or 1;
• Clinical stage at initial diagnosis (per the 8th edition of the American Joint Committee on Cancer Staging Manual): cT1-4/N1-3/M0 (cT1mi/N0 or cT1a-b/N0 are eligible), meeting the criteria for neoadjuvant therapy as per NCCN 2022 guidelines;
• Histologically confirmed hormone receptor-positive (estrogen receptor ≥1% and/or progesterone receptor ≥1%) and HER2-positive (immunohistochemistry 3+ or fluorescence in situ hybridization-positive) invasive breast cancer;
• Completion of ≥4 cycles of neoadjuvant therapy with trastuzumab and pertuzumab, without recurrence or metastatic disease prior to adjuvant treatment; residual cancer burden class 0 or I after neoadjuvant therapy; time from initial surgery to randomization ≤12 weeks;
• Adequate organ function within 2 weeks prior to screening (without transfusion or use of growth factors):
• Absolute neutrophil count ≥1.5 × 10⁹/L;
• Platelet count ≥90 × 10⁹/L;
• Hemoglobin ≥90 g/L;
• Total bilirubin ≤1.5 × upper limit of normal (ULN);
• Alanine aminotransferase and aspartate aminotransferase ≤1.5 × ULN;
• Post-neoadjuvant therapy echocardiography showing left ventricular ejection fraction (LVEF) ≥50% during screening, with an absolute decrease of ≤15% compared to pre-chemotherapy values; if no pre-chemotherapy LVEF assessment is available, LVEF must be ≥55% during screening;
• Life expectancy ≥6 months;
• For premenopausal or non-sterilized female patients: agreement to abstain from sexual activity or use effective non-hormonal contraception during study treatment and for 8 weeks after the last dose;
• Willingness to participate voluntarily, provide signed informed consent, demonstrate good compliance, and cooperate with follow-up.

You may not qualify if:

• History of local or regional breast cancer recurrence;
• Clinical stage IV (metastatic) breast cancer;
• Bilateral breast cancer;
• History of other malignant tumors within the past 5 years, except for curatively treated cervical carcinoma in situ, basal cell carcinoma, or cutaneous squamous cell carcinoma;
• Prior treatment with pyrotinib, lapatinib, neratinib, or other tyrosine kinase inhibitors; trastuzumab emtansine; or any antitumor biological or immunotherapy;
• Concurrent participation in another clinical trial involving antitumor therapy, including endocrine therapy, bisphosphonate therapy, or immunotherapy;
• Significant cardiac disease, including:
• Heart failure or systolic dysfunction (LVEF \< 50%);
• Poorly controlled arrhythmias (e.g., atrial tachycardia, significant ventricular arrhythmia, or high-grade atrioventricular block);
• Angina requiring antianginal medication;
• Clinically significant valvular heart disease;
• Electrocardiographic evidence of transmural myocardial infarction;
• Poorly controlled hypertension (systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 100 mmHg) despite medication;
• Impaired drug absorption due to dysphagia, intestinal obstruction, or other gastrointestinal disorders;
• History of neurological or psychiatric conditions that may compromise compliance or informed consent;

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-sen University Sun Yat-sen Memorial Hospital

Guangzhou, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; neratinib; pertuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Chang Gong

CONTACT

13925089353; gchang@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief physician

Study Record Dates

• First Submitted: February 26, 2023
• First Posted: March 8, 2023
• Study Start: March 14, 2023
• Primary Completion (Estimated): February 16, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)