A Randomized, Open Label, Multi-center 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
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 136
- Locations
- 1
- Primary Endpoint
- Total pathological complete response rate (tpCR) rate
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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;
Arms & Interventions
ARX788 + pyrotinib maleate
ARX788 1.5 mg/kg intravenously (IV) every three weeks plus pyrotinib maleate 320 mg orally once daily for 6 cycles
Intervention: ARX788 (Drug)
ARX788 + pyrotinib maleate
ARX788 1.5 mg/kg intravenously (IV) every three weeks plus pyrotinib maleate 320 mg orally once daily for 6 cycles
Intervention: Pyrotinib maleate (Drug)
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
Intervention: Trastuzumab (Drug)
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
Intervention: Pertuzumab (Drug)
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
Intervention: Docetaxel (Drug)
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
Intervention: Carboplatin (Drug)
Outcomes
Primary Outcomes
Total pathological complete response rate (tpCR) rate
Time Frame: 3 years
The standard for removal of breast and lymph node tumors which means there are no infiltrating cancer cells at the primary breast and axillary lymph nodes, and only intraductal cancer is allowed on the breast.
Secondary Outcomes
- Breast pathological complete response rate (bpCR) rate(3 years)
- Residual tumor burden (RCB)(3 years)
- Best overall response rate (BORR)(3 years)
- Five-year overall survival (OS)(5 years)
- Event-free survival (EFS)(3 years)
- Adverse events (AE)(3 years)
Investigators
Caigang Liu
Director of the Cancer Center
Shengjing Hospital