A Randomized, Controlled, Open-label, Multi-center, Phase IIb/III Clinical Study to Evaluate BEBT-209 Plus Carboplatin and Gemcitabine Versus Carboplatin Plus Gemcitabine in Locally Advanced or Metastatic Triple-Negative Breast Cancer
Title: A Study to See if BEBT-209 Combined With Chemotherapy Works to Treat People With Triple-Negative Breast Cancer Researchers want to learn if a new drug called BEBT-209 works to treat people with a specific type of breast cancer. This cancer is called locally advanced or metastatic triple-negative breast cancer (TNBC). The study has two parts. In the first part, researchers want to see if the new drug combination can shrink tumors. In the second part, researchers want to see if this treatment helps people live longer. Researchers will put participants into two groups by chance. This is like flipping a coin. Group 1: Participants get BEBT-209 plus two chemotherapy drugs. These drugs are Carboplatin and Gemcitabine. Group 2: Participants get only the two chemotherapy drugs. Researchers will group people based on the treatments they had in the past. Researchers will also check: How long the treatment keeps the cancer from growing. This is called progression-free survival (PFS). If the treatment is safe. Researchers will look for adverse events (AE), such as low blood cell counts. How participants feel. This is called health-related quality of life (HRQoL). How the body uses the drug.
⁃ Participants must meet all of the following criteria to be eligible for the study:
• Age and gender: Female, aged 18 to 75 years (inclusive).
• Informed consent: Voluntarily signed the written informed consent form (ICF).
• Diagnosis: Pathologically confirmed hormone receptor (HR)-negative and human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic triple-negative breast cancer (TNBC).
• HR-negative: \<1% of nuclei stain positive for estrogen receptor (ER) and progesterone receptor (PR) by immunohistochemistry (IHC). HER2-negative: IHC 0, 1+, or IHC 2+ with negative in situ hybridization (ISH).
• Prior therapy: Must have received at least one but no more than two prior systemic therapies for unresectable locally advanced or metastatic disease. Progression within 12 months of completion of neoadjuvant/adjuvant therapy is considered one line of systemic therapy.
• Measurable disease: At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
• Performance status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with stable status within 2 weeks prior to screening (clinically insignificant decline).
• Life expectancy: At least 12 weeks.
• Organ function: Adequate organ and bone marrow function (no blood transfusion or growth factors within 2 weeks prior to screening):
⁃ (1)Absolute neutrophil count (ANC) ≥ 1,500/mm³; (2) Platelets ≥ 100,000/mm³; (3) Hemoglobin ≥ 9 g/dL; (4) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (or ≤ 5.0 × ULN with liver metastases); (5) Total bilirubin ≤ 1.5 × ULN (or ≤ 3 × ULN with liver metastases); (6) Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min (Cockcroft-Gault).
• Toxicity recovery: Prior anti-cancer therapy toxicities resolved to ≤ grade 1 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 6.0 (excluding alopecia or other stable toxicities deemed safe by the investigator).
• Contraception: Negative serum pregnancy test within 7 days before treatment for women of childbearing potential. Agree to use highly effective contraception during the study and for 6 months after the last dose.
⁃ Note: The initial documentation of locally advanced or metastatic disease must be supported by biopsy, pathology, or imaging reports with specific dates. Systemic therapy includes systemic treatments for TNBC, such as chemotherapy, targeted therapy, and immunotherapy.