A Phase II Study to Evaluate the Efficacy and Safety of Anti-HER2 Triple-targeted Drugs Combined With CDK4/6 Inhibitors in Neoadjuvant Therapy for ER-positive HER2-positive Breast Cancer Patients.

NCT07290166 | Not Yet Recruiting Phase 2

• 1 other identifier: SCHBCC-N098
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

Brief Summary

To further enhance treatment efficacy, minimize reliance on chemotherapy, and identify the optimal neoadjuvant approach for ER-positive and HER2-positive population, we have designed a single-arm, phase II clinical trial. This study aims to evaluate the efficacy and safety of a novel regimen integrating CDK4/6 inhibitors intensified endocrine therapy and dual HER2-targeted monoclonal antibodies plus the tyrosine kinase inhibitor pyrotinib.

Conditions

Breast Cancer

Keywords

ER positive and HER2 positive; triple-targeted anti-HER2 strategy; chemotherapy-free; neoadjuvant

Outcome Measures

Primary Outcomes (1)

• pCR

  pathological response rate

  3 years

Secondary Outcomes (6)

• EFS

  3 years

• iDFS

  3 years

• RFS

  3 years

• DDFS

  3 years

• OS

  3 years

Study Arms (1)

triple-targeted anti-HER2

EXPERIMENTAL

trastuzumab, pertuzumab, and pyrotinib combined with CDK4/6 inhibitor and endocrine therapy

Drug: triple-targeted anti-HER2 and CDK4/6 inhibitor

Interventions

triple-targeted anti-HER2 and CDK4/6 inhibitor DRUG

trastuzumab, pertuzumab, and pyrotinib combined with CDK4/6 inhibitor and endocrine therapy

triple-targeted anti-HER2

Eligibility Criteria

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

You may qualify if:

• Women aged 18 to 70 years with breast cancer eligible for neoadjuvant therapy
• Clinically staged as II-III
• Histologically confirmed unilateral invasive breast cancer with HER2 positivity, defined as HER2 immunohistochemistry 3+ or in situ hybridization (FISH)-confirmed amplification
• Estrogen receptor (ER) expression ≥10% by immunohistochemistry
• Postmenopausal status
• Premenopausal or perimenopausal patients must undergo surgical oophorectomy or receive ovarian function suppression with gonadotropin-releasing hormone (GnRH) agonists
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Left ventricular ejection fraction (LVEF) ≥50% and corrected QT interval (QTc) ≤470 ms
• Adequate major organ function, as evidenced by the following laboratory parameters:
• (1) Hematologic function: hemoglobin (Hb) ≥90 g/L (without transfusion within 14 days), absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥100×10⁹/L; (2) Hepatic and renal function: total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN, serum creatinine ≤1×ULN, and calculated creatinine clearance \>50 mL/min using the Cockcroft-Gault formula 10) Willingness to participate in the study, provision of signed informed consent, and demonstrated ability to comply with study procedures and follow-up visits

You may not qualify if:

• HER2-negative disease, defined as immunohistochemistry (IHC) score of 0 or 1+; or IHC 2+ without amplification by fluorescence in situ hybridization (FISH)
• Prior receipt of neoadjuvant therapy or any systemic or non-surgical local treatment, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy
• History of another malignancy, except for adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ
• Inflammatory breast cancer, bilateral breast cancer, or presence of distant metastases
• Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use effective contraception during the study period
• Concurrent participation in another interventional clinical trial
• Significant organ dysfunction, including cardiac, pulmonary, hepatic, or renal impairment; left ventricular ejection fraction (LVEF) \<50% on echocardiography; history of major cardiovascular or cerebrovascular events within 6 months prior to enrollment (e.g., unstable angina, chronic heart failure, myocardial infarction, or stroke); uncontrolled hypertension (\>150/90 mmHg); or poorly controlled diabetes mellitus
• Current use of strong CYP3A4 inhibitors or inducers, including:
• Strong inhibitors: boceprevir, clarithromycin, conivaptan, delavirdine, indinavir, itraconazole, ketoconazole, ritonavir, mibefradil, miconazole, trazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, voriconazole, grapefruit, grapefruit juice, or grapefruit-containing products
• Strong inducers: carbamazepine, phenytoin, primidone, rifampicin, and St. John's wort
• Active, severe, or uncontrolled infection, or fever of unknown origin during the screening period
• History of substance abuse involving psychotropic agents with ongoing dependence, or history of significant psychiatric disorder that may impair compliance or safety
• Deemed unsuitable for study participation by the treating investigator

Sponsors & Collaborators

• Fudan University: lead

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Zhimin Shao, MD, PhD

CONTACT

02164175590; zhimingshao@yahoo.com

Yin Liu, MD

CONTACT

02164175590; liuyinfudan@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 6, 2025
• First Posted: December 18, 2025
• Study Start: December 31, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): April 30, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share