Early-stage Breast CancerPhase 3NCT05760612
Adjuvant Trastuzumab Plus Neratinib in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer After Neoadjuvant Trastuzumab Plus Pertuzumab
A Phase 3 study testing Trastuzumab and neratinib and Trastuzumab and Pertuzumab in people with Early-stage Breast Cancer and HER2-positive Breast Cancer, run by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Early-stage Breast Cancer, HER2-positive Breast Cancer, Adjuvant Treatment After Trastuzumab
- What is being tested?
- Trastuzumab and neratinib and Trastuzumab and Pertuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- 14 Mar 2023to 1 Nov 2028
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
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- 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.
Who cannot join
- 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;
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- 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;
- Chronic gastrointestinal disorders with predominant diarrhea;
- Known hypersensitivity to any study drug components; history of immunodeficiency (e.g., HIV positivity, congenital or acquired immunodeficiency disorder), or prior organ transplantation;
- Pregnancy, lactation, or positive pregnancy test at baseline in women of childbearing potential;
- Severe comorbidities that may interfere with treatment, including active infections (e.g., hepatitis B, hepatitis C, tuberculosis, syphilis) or any other condition deemed by the investigator to render the patient unsuitable for trial participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Sun Yat-sen Memorial Hospital
Guangzhou
chang Gong, 13925089353, gchang@mail.sysu.edu.cn
About this study
Official title: A Randomized, Open-Label, Phase III Trial Comparing Adjuvant Trastuzumab Plus Neratinib Versus Trastuzumab Plus Pertuzumab in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer With Residual Cancer Burden 0/I After Neoadjuvant Trastuzumab Plus Pertuzumab
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
- Being tested
- Trastuzumab and neratinib, Trastuzumab and Pertuzumab
- Keywords
- Hormone receptor positive HER2 positive breast cancer, targeted therapy, adjuvant therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trastuzumab and neratinibDrug
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 and PertuzumabDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Trastuzumab and neratinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: During the 3 years after random assignment
Secondary outcomes (4)
Disease free survival, DFS
The time from random assignment until recurrence, the development of a second cancer, or death from any cause.
Measured: During the 3 years after random assignment
Overall survival, OS
The time from randomization to death from any cause.
Measured: During the 3 years after random assignment
Distant disease free survival, DDFS
The time from random assignment until the first occurrence of distant recurrence or death from any cause.
Measured: During the 3 years after random assignment
Incidence and severity of adverse events
The incidence and severity of adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).
Measured: From signing the informed consent form until 28 days after completion of adjuvant treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2023
- Study start14 Mar 2023
- Primary completion16 Feb 2028 (estimated)
- Study completion1 Nov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Early-stage Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chang Gong, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05760612
- Sponsor's protocol ID
- SYSKY-2023-075-03
- Status last verified
- Sep 2025
- First submitted
- 26 Feb 2023
- Last updated
- 25 Sep 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No