Neoadjuvant Oral Paclitaxel Plus Subcutaneous Pertuzumab/Trastuzumab in Patients With HER2-positive Breast Cancer

A Single-Arm Clinical Study to Evaluate the Efficacy and Safety of Neoadjuvant Oral Paclitaxel Plus Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients With HER2-positive Breast Cancer

The goal of this clinical trial is to evaluate the efficacy and safety of oral paclitaxel plus fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in the neoadjuvant treatment of HER2+ breast cancer patients.

OPTIMAL-BC is a multicenter, single arm study using a Simon's two-stage design evaluating neoadjuvant treatment with paclitaxel oral solution combined with subcutaneous fixed dose combination (FDC) of pertuzumab and trastuzumab every 3 weeks for 6 cycles. All subjects will undergo surgery in line with local guidelines following neoadjuvant therapy. The primary endpoint is total pathological complete response(tpCR, ypT0/is, ypN0).

Inclusion Criteria:

Aged 18-75 years old. Histologically confirmed HER2-positive invasive breast cancer with clinical stages T1c-4, N0-3, and M0 (excluding T1cN0M0), according to the 8th American Joint Committee on Cancer (AJCC) edition BC staging system HER2 overexpression was defined as immunohistochemistry (IHC) 3+ or 2+ with HER2 gene amplification, determined by fluorescence in situ hybridization (FISH).

Baseline left ventricular ejection fraction (LVEF) of ≥50%. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.

The functional level of major organs must meet the following requirements (no blood transfusion and no use of white blood cell, red blood cell and platelet-raising drugs within 2 weeks before the first dose):

• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase and aspartate aminotransferase (ALT/AST) ≤1.5×ULN
• Blood urea nitrogen and serum creatinine ≤1.5×ULN
• Creatinine clearance (Ccr) ≥50 ml/min (Cockcroft-Gault formula) Signature of informed consent

Exclusion Criteria:

• History of invasive breast cancer. Bilateral breast cancer or inflammatory breast cancer . Prior excisional and/or incisional biopsy of the primary tumor and/or axillary lymph nodes.

Prior systemic therapy for breast cancer. History of life-threatening hypersensitivity reactions or known hypersensitivity to any component of the investigational drug.

Participation in another clinical trial of a drug or medical device within 4 weeks prior to the first dose and/or receipt of investigational drug/device during the trial.

Major surgery within 28 days prior to the first dose or planned major surgery during the study period.

History of other malignancies within the past 5 years, except for carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer, or ductal carcinoma in situ.

Active tuberculosis or other severe infectious diseases requiring systemic treatment, including but not limited to bacteremia, severe pneumonia, and other serious infections.

History of immunodeficiency or autoimmune diseases, including but not limited to HIV infection (HIV antibody positive), systemic lupus erythematosus, rheumatoid arthritis, or history of organ transplantation.

History of cardiovascular or cerebrovascular diseases, including:

• Unstable angina;
• Clinically significant arrhythmias requiring medication;
• Myocardial infarction within the past 6 months;
• Heart failure or second-degree or higher atrioventricular block;
• Cerebral infarction (excluding lacunar infarction) or cerebral hemorrhage within the past 6 months.

Poorly controlled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg despite regular medication), or history of hypertensive crisis or hypertensive encephalopathy.

Unsuitability for oral administration of the investigational drug, as judged by the investigator, including:

• Clinically significant or uncontrolled congenital or acquired gastrointestinal diseases;
• Diseases that may affect drug administration, gastric entry, or absorption (e.g., intestinal obstruction, Crohn's disease, ulcerative colitis).

Pregnant or breastfeeding women; women of childbearing potential with a positive pregnancy test at screening; or those unwilling to use effective contraception during the study and for 6 months after the last dose.