Neoadjuvant Pyrotinib in HR-positive and HER2-low High-risk Early Breast Cancer

Neoadjuvant Pyrotinib Combined With Chemotherapy Versus Chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) High-risk Early Breast Cancer: an Open-lable, Multi-center, Randomized Phase III Trial

This is a multi-center, open-lable, prospective, randomized phase III clinical trial to further validate the efficacy and safety of neoadjuvant pyrotinib combined with chemotherapy in HR-positive/HER2-low (IHC 2+/FISH-negative) high-risk early breast cancer

Study Overview

• Status: Active, not recruiting
• Conditions: Early-stage Breast Cancer; Breast Cancer Invasive; HER2 Low Breast Carcinoma; Hormone-receptor-positive Breast Cancer
• Intervention / Treatment: Drug: Pyrotinib, epirubicin or doxorubicin, cyclophosphamide, paclitaxel; Drug: Epirubicin or doxorubicin, cyclophosphamide, paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Must participate voluntarily, sign the informed consent form, and have good compliance
• Aged ≥ 18 and ≤ 70 years old with ECOG PS score of 0-1
• Histopathological newly diagnosed, unilateral, primary invasive breast cancer
• Histopathological hormone receptor-positve ( estrogen receptor and/or progesterone receptor ≥ 10% stained cells) and HER2-low (immunochemistry 2+ with fluorescent in situ hybridization negative)
• TNM stage-IIb/III, or TNM stage-IIa with high risk (N+, G3, or MammaPrint High-risk)
• At least one evaluable target breast lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Left ventricular ejection fraction ≥ 55%, Fridericia-corrected QT interval < 450 ms in males and < 470 ms in females
• White blood cell count: ≥ 3.0 × 10^9/L, absolute neutrophil count: ≥ 1.5 × 10^9/L, platelet count: ≥ 100 × 10^9/L, hemoglobin: ≥ 90 g/L
• Aspartate aminotransferase and alanine aminotransferase: ≤ 2.5 × ULN, alkaline phosphatase: ≤ 2.5 × ULN, blood total bilirubin: ≤ 1.5 × ULN, serum creatinine: ≤ 1.5 × ULN
• Non-menopausal or non-surgically sterilized female patients identified as non-pregnant and non-lactating and consented to contraception both during the trial and within 6 months after the last administration of the test drug

Exclusion Criteria:

• Metastatic BC, bilateral BC, occult BC, inflammatory BC, or with other malignant tumors
• Known history of hypersensitivity to the study drugs
• Patients who need receive other anti-tumor treatments (except for OFS) during neoadjuvant therapy as judged by the investigators
• With severe cardiac disease or discomfort that is not expected to tolerate treatment, including but not limited to: a) arrhythmia that requires medication or is clinically significant, or high-grade atrioventricular block, b) unstable angina, myocardial infarction, heart failure or clinically significant heart valve disease, c) poorly controlled hypertension or any heart disease unsuitable for participation in this trial as determined by the investigators
• Patients who participated in a clinical trial of another drug within 4 weeks prior to randomization or underwent BC-free surgery within 4 weeks or had not fully recovered after BC-free surgery
• Other malignancy in the past 5 years, other than cured cervical carcinoma in situ, basal or squamous cell carcinoma of skin
• Patients who had basic gastrointestinal diseases (especially long-term history of diarrhea or/and constipation), inability to swallow, intestinal obstruction or other factors will affect drugs administration and absorption
• Presence of accompanying diseases that may pose serious risks to the safety of the patient or may affect the patient's ability to complete the study (including but not limited to severe diabetes mellitus, active infection, thyroid disorders, etc.) as judged by the investigator
• With a history of immunodeficiency, including acquired or congenital immunodeficiencies, or a history of organ transplantation
• Past history of confirmed neurological or mental disorders, including epilepsy or dementia
• Other conditions of the subject determined by the investigator to be unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant pyrotinib combined with chemotherapy	Drug: Pyrotinib, epirubicin or doxorubicin, cyclophosphamide, paclitaxel; Pyrotinib 320 mg orally once daily, and epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.
Placebo Comparator: Neoadjuvant chemotherapy	Drug: Epirubicin or doxorubicin, cyclophosphamide, paclitaxel; Epirubicin 90 mg/m² or doxorubicin 60 mg/m² plus cyclophosphamide 600 mg/m² intravenously on day 1 for four 3-week cycles followed by paclitaxel 175 mg/m² intravenously on day 1 or four 3-week cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Cancer Burden 0/1 rate as assessed by independent central review	The proportion of patients with RCB 0/I after neoadjuvant therapy according to the online Residual Cancer Burden Calculator provided by the MD Anderson Cancer Center as assessed by independent central review	Within 4 weeks after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Residual Cancer Burden 0/1 rate as assessed by local pathology review	The proportion of patients with RCB 0/I after neoadjuvant therapy according to the online Residual Cancer Burden Calculator provided by the MD Anderson Cancer Center as assessed by local pathology review	Within 4 weeks after surgery
Pathological complete response rate	The proportion of patients with no residual invasive tumor cells in the breast and axillary nodes, regardless of ductal carcinoma in situ	Within 4 weeks after surgery
Objective response rate	The percentage of patients who achieved a complete or partial response in breast according to the RECIST, version 1.1, based on MRI, at the end of cycle 2 neoadjuvant therapy and at the end of cycle 8 neoadjuvant therapy	Within 2 weeks of breast MR examination
Breast conservation surgery rate	The proportion of patients who had successful breast conservation surgery after neoadjuvant therapy	Within 4 weeks after surgery
Health-related Quality of Life 1	The score of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (version 3)	Within 7 days before the first treatment and the end of each cycle (each cycle is 21 days)
Health-related Quality of Life 2	The score of Breast Cancer-Specific Module (QLQ-BR23)	Within 7 days before the first treatment and the end of each cycle (each cycle is 21 days)
5-year event-free survival	the time from random assignment until any relapse, unequivocal tumor progression, or any-cause death	During the 5 years after random assignment
5-year overall survival	the time from random assignment until any-cause death	During the 5 years after random assignment
Safety (AEs+SAEs)	General safety will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Ovarian toxicity will be evaluated by menstrual status and FSH and E2	from signing the informed consent form until 2 years after completion of neoadjuvant treatment
Biomarkers (Immune cell subpopulations quantities)	The association between immune cell subpopulations quantities and RCB	Within 4 weeks after surgery

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
• Collaborators: Jiangsu HengRui Medicine Co., Ltd.
• Investigators: Principal Investigator: Chang Gong, Prof, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): January 17, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: November 14, 2023
• First Submitted That Met QC Criteria: November 17, 2023
• First Posted (Actual): November 22, 2023

Study Record Updates

• Last Update Posted (Actual): January 30, 2026
• Last Update Submitted That Met QC Criteria: January 29, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: neoadjuvant; HR-positive; pyrotintb; HER2-low EBC
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Carbohydrates; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glycosides; Taxoids; Cyclodecanes; Diterpenes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Anthracyclines; Naphthacenes; Aminoglycosides; Daunorubicin; Cyclophosphamide; Doxorubicin; Paclitaxel; Epirubicin; pyrotinib
• Other Study ID Numbers: PILHLE-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in future research article after de-identification and the study protocol will be shared beginning 3 months and ending 5 years following publication. Proposals should be directed to gchang@mail.sysu.edu.cn and data will be shared by email
• IPD Sharing Time Frame: beginning 3 months and ending 5 years following publication of future research article
• IPD Sharing Access Criteria: Researchers who provide a methodologically sound proposal, that need to be approved by an approved accredited ethics committee
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No