Randomized Controlled Clinical Study of Efficacy and Safety of Initumab Combined with Pyrrotinib and Chemotherapeutic Agents in Neoadjuvant Therapy for HER2-positive Breast Cancer with Different Treatment Cycles

The purpose of this study was to explore the efficacy and safety of initumab combined with pyrrotinib and chemotherapy for 4 cycles and 6 cycles of neoadjuvant therapy for HER2-positive breast cancer, and to explore the efficacy and safety of continued use of initumab combined with pyrrotinib in pCR patients.

This study adopted A prospective, randomized controlled, open-label design, and selected eligible subjects to be randomly divided into cohort A and Cohort B. Cohort A will receive initumab at initial load dose of 8mg/kg and maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 4 doses. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 4 cycles of administration. After surgery for breast cancer, initumab + pyrrotinib was selected as adjuvant therapy for pCR patients after surgery for 1 year (neoadjuvant therapy + adjuvant therapy for a total of 1 year, a total of 13 cycles of adjuvant therapy), and non-pCR patients were selected by doctors. Cohort B will receive initumab at initial load dose of 8mg/kg and maintenance dose of 6mg/kg intravenously on the first day of every three weeks. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 6 cycles of administration. After surgery for breast cancer, initumab + pyrrotinib was selected as adjuvant therapy for pCR patients after surgery for 1 year (neoadjuvant therapy + adjuvant therapy for a total of 1 year, and adjuvant therapy for a total of 11 cycles), and non-pCR patients were selected by doctors.

Study Overview

• Status: Not yet recruiting
• Conditions: HER2 Positive Breast Cancer
• Intervention / Treatment: Drug: Cohort A will receive an initial load dose of 8mg/kg and a maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 4 doses; Drug: Cohort B will receive an initial load dose of 8mg/kg and a maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 6 doses

• Study Type: Interventional
• Enrollment (Estimated): 208
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: dongsong S dongsong; Phone Number: +8613943189777; Email: songdong117@126.com

Participation Criteria

Eligibility Criteria

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

Description

inclusion criteria：

1. Age ≥18 years old, while ≤70 years old, gender is not limited; 2.2. Invasive breast cancer confirmed histologically by air-core needle biopsy; According to AJCC breast cancer Staging System 8th edition, clinical staging was T1c-4, N0-3, M0.

3. HER2 positive: IHC 3+ or IHC 2+ and FISH+ 4.Left ventricular ejection fraction (LVEF) ≥ 50% 5.ECOG physical condition score is 0 or 1 6.In the absence of blood transfusion or symptomatic treatment (granulocyte colony-stimulating factor/erythropoietin (EPO)/interleukin-11, etc.) within 14 days prior to initial administration, organ function must meet the following requirements Blood routine: absolute value of neutrophil (ANC) ≥1.5×109/L; Platelet (PLT) ≥100×109/L; Hemoglobin (Hb) ≥90g/L Blood biochemistry: Total bilirubin (TBIL) ≤1.5×ULN; ALT and AST≤1.5×ULN; BUN and Cr≤1.5×ULN; Creatinine clearance ≥50mL/min (Cockcroft-Gault formula) 7.Voluntarily participate in this study, sign informed consent, have good compliance and are willing to cooperate with follow-up

exclusion criteria:

1. Previous history of invasive breast cancer
2. Bilateral breast cancer, inflammatory breast cancer (e.g., erythema and/or skin involvement, and/or pathological findings of tumor cells in the dermal lymphatic vessels), or clinical stage T1c, N0, M0
3. Prior biopsy of primary tumor and/or axillary lymph node excision and/or excision
4. Previous systemic treatment for breast cancer;
5. A history of life-threatening hypersensitivity, or a known history of allergy to any component of the investigational drug;
6. Participated in clinical trials of other drugs or medical devices within 4 weeks before the first drug use, and received treatment with experimental drugs or devices
7. Patients who had undergone major surgery within 28 days prior to the first dose or planned to undergo major surgery during the study period
8. Other malignant tumors (excluding cervical carcinoma in situ, non-melanoma skin cancer, localized prostate cancer, ductal carcinoma in situ) within the previous 5 years
9. Active hepatitis, active tuberculosis or other serious infectious diseases, including but not limited to: Active hepatitis C virus (HCV) infection (HCV antibody positive but not RNA negative), or hepatitis B virus (HBV) infection (HBV surface antigen positive and HBV-DNA copy number >2000 IU/mL) or other serious infections requiring systemic treatment such as bacteremia, severe infectious pneumonia
10. A history of immunodeficiency or other autoimmune diseases, including but not limited to human immunodeficiency virus (HIV) infection (HIV-positive), systemic lupus erythematosus, rheumatoid arthritis, or a history of organ transplantation
11. Patients with a history of cardiovascular and cerebrovascular diseases, including: (1) unstable angina pectoris; (2) medically treatable or clinically significant arrhythmias; (3) myocardial infarction occurring within 6 months; (4) Heart failure, degree II and above atrioventricular block; (5) Cerebral infarction (except lacunar cerebral infarction), cerebral hemorrhage and other diseases occurring within 6 months
12. Patients with poorly controlled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg under regular medication), or with a prior history of hypertensive crisis or hypertensive encephalopathy
13. Pregnant and lactating female patients; Pregnant women of childbearing age who were positive in screening pregnancy test; Patients who are unwilling to use effective contraception throughout the trial period and for 6 months after the end of medication
14. Other circumstances deemed inappropriate by the investigator to participate in 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
Other: Queue A	Drug: Cohort A will receive an initial load dose of 8mg/kg and a maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 4 doses; Cohort A will receive initumab at initial load dose of 8mg/kg and maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 4 doses. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 4 cycles of administration
Other: Queue B	Drug: Cohort B will receive an initial load dose of 8mg/kg and a maintenance dose of 6mg/kg intravenously on the first day of every three weeks for a total of 6 doses; The initial loading dose of initumab was 8mg/kg, and the maintenance dose was 6mg/kg, which was administered intravenously on the first day of every three weeks. Pyrrotinib 400mg orally once daily; Combined chemotherapy drugs (not limited, according to the actual clinical selection), a total of 6 cycles of administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
total Pathological Complete Response，tpCR	After completion of neoadjuvant therapy, subjects' completely removed breast specimens and all sampled regional lymph nodes were evaluated

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate，ORR	It refers to the percentage of cases that achieved complete response (CR) and partial response (PR) after neoadjuvant therapy as a percentage of the total number of evaluable cases
Event-Free Survival，EFS	Refers to the time from enrollment to the first recorded recurrence of disease, disease progression, or death from any cause after surgery
Invasive Disease-Free Survival，iDFS	Refers to the time from enrollment to the first occurrence of an aggressive ipsilateral tumor recurrence, aggressive countermeasure breast cancer, local/regional aggressive recurrence, distant recurrence, or death from any cause
Overall Survival	Refers to the time from enrollment to death

Collaborators and Investigators

• Sponsor: The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): February 19, 2026
• Study Completion (Estimated): February 19, 2027

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: OBU-BC-II-206

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
• product manufactured in and exported from the U.S.: No