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. (Cinderella-Neo)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: triple-targeted anti-HER2 and CDK4/6 inhibitor

Detailed Description

In patients with ER-positive and HER2-positive breast cancer, the therapeutic potential of combining trastuzumab, pertuzumab, and pyrotinib-representing a triple-targeted anti-HER2 strategy-alongside intensified endocrine therapy( with CDK4/6 inhibitors )has not yet been established. To further enhance treatment efficacy, minimize reliance on chemotherapy, and identify the optimal neoadjuvant approach for this patient 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.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yin Liu, MD; Phone Number: 02164175590; Email: liuyinfudan@163.com
• Study Contact Backup: Name: Zhimin Shao, MD, PhD; Phone Number: 02164175590; Email: zhimingshao@yahoo.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Women aged 18 to 70 years with breast cancer eligible for neoadjuvant therapy
2. Clinically staged as II-III
3. Histologically confirmed unilateral invasive breast cancer with HER2 positivity, defined as HER2 immunohistochemistry 3+ or in situ hybridization (FISH)-confirmed amplification
4. Estrogen receptor (ER) expression ≥10% by immunohistochemistry
5. Postmenopausal status
6. Premenopausal or perimenopausal patients must undergo surgical oophorectomy or receive ovarian function suppression with gonadotropin-releasing hormone (GnRH) agonists
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
8. Left ventricular ejection fraction (LVEF) ≥50% and corrected QT interval (QTc) ≤470 ms
9. 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

Exclusion Criteria:

1. HER2-negative disease, defined as immunohistochemistry (IHC) score of 0 or 1+; or IHC 2+ without amplification by fluorescence in situ hybridization (FISH)
2. Prior receipt of neoadjuvant therapy or any systemic or non-surgical local treatment, including chemotherapy, targeted therapy, radiotherapy, or endocrine therapy
3. History of another malignancy, except for adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ
4. Inflammatory breast cancer, bilateral breast cancer, or presence of distant metastases
5. Pregnant or breastfeeding women, or women of childbearing potential who are unwilling or unable to use effective contraception during the study period
6. Concurrent participation in another interventional clinical trial
7. 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

8. Current use of strong CYP3A4 inhibitors or inducers, including:

   1. 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
   2. Strong inducers: carbamazepine, phenytoin, primidone, rifampicin, and St. John's wort
9. Active, severe, or uncontrolled infection, or fever of unknown origin during the screening period
10. History of substance abuse involving psychotropic agents with ongoing dependence, or history of significant psychiatric disorder that may impair compliance or safety
11. Deemed unsuitable for study participation by the treating investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: triple-targeted anti-HER2; trastuzumab, pertuzumab, and pyrotinib combined with CDK4/6 inhibitor and endocrine therapy	Drug: triple-targeted anti-HER2 and CDK4/6 inhibitor; trastuzumab, pertuzumab, and pyrotinib combined with CDK4/6 inhibitor and endocrine therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pCR	pathological response rate	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	3 years
adverse events	adverse events according to CTCAE 5.0	3 years
EFS	Event free survival	3 years
iDFS	invasive disease free survival	3 years
RFS	Recurrence free survival	3 years
DDFS	distant disease free survival	3 years

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): December 31, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): April 30, 2028

Study Registration Dates

• First Submitted: December 6, 2025
• First Submitted That Met QC Criteria: December 6, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 6, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: neoadjuvant; ER positive and HER2 positive; triple-targeted anti-HER2 strategy; chemotherapy-free
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms
• Other Study ID Numbers: SCHBCC-N098

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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