A Study of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) as Neoadjuvant Treatment in HER2-positive Breast Cancer Patients

NCT ID: NCT05426486

Last Updated: 2024-10-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 136 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-23
• Study Completion Date: 2028-12-30

Brief Summary

This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer.

Detailed Description

This is a randomized, open label Phase II-III neoadjuvant study comparing the efficacy and safety of ARX788 combined with pyrotinib maleate versus TCBHP (trastuzumab plus pertuzumab with docetaxel and carboplatin) in patients with HER2-positive breast cancer. Patients will be randomized (1:1) to one of the two treatment arms: arm 1, ARX788 plus pyrotinib maleate for 6 cycles; arm 2, trastuzumab plus pertuzumab with docetaxel and carboplatin for six cycles. Patients will undergo surgery after neoadjuvant therapy. Efficacy will be assessed every 2 cycles.

Conditions

HER2-positive Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ARX788 + pyrotinib maleate

ARX788 1.5 mg/kg intravenously (IV) every three weeks plus pyrotinib maleate 320 mg orally once daily for 6 cycles

Group Type: EXPERIMENTAL

ARX788

Intervention Type: DRUG

HER2 antibody-drug conjugate

Pyrotinib maleate

Intervention Type: DRUG

EGFR/HER2 dual inhibitor

trastuzumab + pertuzumab + docetaxel + carboplatin

Trastuzumab (8 mg/kg first dose, followed 6 mg/kg) puls pertuzumab (840 mg first dose, followed 420 mg) plus docetaxel (75 mg/m3) plus carboplatin (AUC6) IV every 3 weeks for 6 cycles

Group Type: ACTIVE_COMPARATOR

Trastuzumab

Intervention Type: DRUG

anti-Her2 monoclonal antibody

Pertuzumab

Intervention Type: DRUG

anti-HER2 monoclonal antibody

Docetaxel

Intervention Type: DRUG

Cytotoxic chemotherapy

Carboplatin

Intervention Type: DRUG

Cytotoxic chemotherapy

Interventions

ARX788

HER2 antibody-drug conjugate

Intervention Type: DRUG

Pyrotinib maleate

EGFR/HER2 dual inhibitor

Intervention Type: DRUG

Trastuzumab

anti-Her2 monoclonal antibody

Intervention Type: DRUG

Pertuzumab

anti-HER2 monoclonal antibody

Intervention Type: DRUG

Docetaxel

Cytotoxic chemotherapy

Intervention Type: DRUG

Carboplatin

Cytotoxic chemotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Female patients aged ≥ 18 but ≤ 75 years;
• Diagnosis of breast cancer meets the following criteria: Histologically confirmed invasive breast cancer; Tumor staging: Stage II-III patients who meet the 8th edition of AJCC Cancer Staging Manual;
• HER2-positive breast cancer pathologically confirmed is defined as Immunohistochemical method (IHC 3+) or IHC 2+ with FISH+;
• Eastern Cooperative Oncology Group (ECOG) level 0-1;
• The functional level of major organs must conform to the following requirements: Neutrophils (ANC) ≥ 1.5×10^9/L (with no use of growth factors within 14 days); Platelet count (PLT) ≥ 100×10^9/L (with no correct treatment within 7 days ); Hemoglobin (Hb) ≥ 90 g/L (with no correct treatment within 7 days ); Total bilirubin (TBIL) ≤ 1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3×ULN; Urea nitrogen and creatinine ≤ 1.5×ULN and creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula); Cardiac color Doppler ultrasound: left ventricular ejection fraction (LVEF) ≥ 50%; 12-lead electrocardiogram: QT interval ≤ 480 ms;
• Patients who participate in the trial voluntarily, sign an informed consent, have good compliance and are willing to comply with the follow-up visit.

Exclusion Criteria

• Previously received any anti-tumor therapy (chemotherapy, radiotherapy, molecular targeted therapy, endocrine therapy, etc.);
• Patients who are concurrently receiving other anti-tumor therapy;
• Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer;
• Stage IV breast cancer;
• With a history of any malignancies other than breast cancer in the past 5 years, excluding cured cervical carcinoma in situ and melanoma skin cancer;
• Inability to swallow, chronic diarrhea and intestinal obstruction, and having many factors that affect drug administration and absorption;
• Patients with known allergies to any active ingredients or excipients of Investigational medicinal product;
• With a history of interstitial pulmonary disease, drug-induced pulmonary interstitial disease, and radiation pneumonitis that require hormone therapy, or any clinically active pulmonary interstitial disease as suggested by any evidence;
• Patients who are currently suffering from keratitis, corneal disease, retinal disease, or active eye infection that require any interventions for the eyes;
• Once suffered from any heart disease, including: (1) arrhythmia with clinical significance, (2) myocardial infarction; (3) heart failure; (4) investigator's judgment as not suitable for participating in this trial;
• Female patients during pregnancy and lactation, or those who are fertile and positive for baseline pregnancy test or those of childbearing age who are unwilling to take effective contraceptive measures throughout the trial period;
• Serious concomitant diseases or other comorbid diseases that will endanger the safety of patients or interfere with the completion of the trial, including but not limited to severe hypertension, severe diabetes mellitus, and active infections that are out of control;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Caigang Liu

OTHER

Sponsor Role: lead

Responsible Party

Caigang Liu

Director of the Cancer Center

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Caigang Liu, MD

Role: PRINCIPAL_INVESTIGATOR

Shengjing Hospital

Locations

Shengjing Hospital affiliated to China Medical University

Shenyang, Liaoning, China

Countries

China

Other Identifiers

MUKDEN 06

Identifier Type: -

Identifier Source: org_study_id