Utidelone Plus Capecitabine Versus Taxane Plus Capecitabine in HER2-negative Locally Advanced or Metastatic Breast Cancer

Prior treatment

• Patients who have received anti-tumor therapy within 4 weeks prior to the start of study treatment, including chemotherapy, radical radiotherapy, hormone therapy, biological therapy, immunotherapy or anti-tumor Chinese medicine therapy;
• Patients who have undergone major organ surgery (excluding needle biopsy) or have significant trauma within 4 weeks before the first dose of treatment, or anticipating for a major surgical procedure during the study;
• Experienced grade 3 or above nervous system-related adverse events after treatment with anti-microtubule drugs;
• Received taxane and/or capecitabine-containing adjuvant/neoadjuvant chemotherapy within 1 year prior to the first study treatment;
• Received prior first-line chemotherapy containing a taxane or capecitabine;
• Inability to take or absorb oral medications;
• Use of corticosteroids is prohibited.

Other illness

• Other malignancies (including primary brain or leptomeninges-related tumors) within the past 5 years, except cured cutaneous basal cell carcinoma and cervical carcinoma in situ;
• Known or suspected hypersensitivity to any of the study drugs or excipients;
• Any other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that precludes study treatment implementation or follow-up ；
• Any other condition that the investigator considers inappropriate to participate in this trial .

Other

• HER-2 positive (IHC + + +, or FISH positive);
• Symptomatic peripheral neuropathy or CTCAE 5.0 grade ≥ 2;
• Symptomatic central nervous system metastases;
• Pregnant or lactating women;

• Signed Informed Consent Form;
• Women aged ≥ 18 years;
• Patients with locally advanced or metastatic, histologically or cytologically documented breast cancer;
• The primary tumor and metastases (if aspirated) are both HER2-negative;
• Eastern Cooperative Oncology Group (ECOG) score \[0-2\] points;
• Measurable disease according to RECIST version 1.1;
• Previous chemotherapy with taxane for early breast cancer (eBC; neoadjuvant or adjuvant setting) is permitted if completed ≥12 months before randomisation;
• No more than one prior chemotherapy regimen for inoperable locally advanced or metastatic HER2-negative breast cancer;
• Hormone receptor positive patients are allowed no more than two lines of prior endocrine therapy for metastatic disease (including CDK4/6 inhibitors, chidamide and PI3K inhibitors, etc.);
• Patients must have recovered to ≤ Grade 1 (CTCAE v5.0) from all toxicities related to prior antineoplastic therapy. However, patients with any grade of alopecia are allowed ;
• Patients with asymptomatic CNS metastases may be enrolled, if:
  • Intracranial lesions are evaluable and eligible for systemic therapy only in the absence of extracranial evaluable lesions, or
  • Patients with stable intracranial lesions after local treatment while there are extracranial evaluable lesions ;
• Adequate hematological, hepatic and renal function;
• Women of child bearing potential must agree to use a contraceptive method during the treatment period and for at least 90 days after the last dose of experiment treatment;
• Life expectancy of at least 12 weeks;
• Patients must be able to participate and comply with treatment and follow-up.