A Study of BEBT-209 in Combination With Chemotherapy for the Treatment of Advanced Triple-Negative Breast Cancer

Inclusion Criteria:

1. Age: ≥18 years old, female;

2. The subject has fully understood and is willing to sign the Informed Consent Form (ICF);

3. Confirmed diagnosis of HR-negative, HER2-negative locally recurrent or metastaticbreast cancer by pathological biopsy;

4. Estrogen and progesterone receptor immunohistochemical assessment of tumor tissue isnegative (defined as <1% nuclear staining), and HER2 is negative (i.e., nooverexpression, including local immunohistochemical assessment [0 or 1+], orimmunohistochemical assessment [2+] with negative in situ hybridization testing);

5. The subject has previously received 1-2 lines of systemic treatment (if progressionwithin 12 months after the last treatment of adjuvant/new adjuvant, it can beconsidered as one line of treatment);

6. At least one measurable lesion in accordance with Response Evaluation Criteria inSolid Tumors (RECIST) 1.1 criteria;

7. Eastern Cooperative Oncology Group (ECOG) score of 0-1 , and no decline in physicalperformance in the past two weeks;

8. Life expectancy of at least 12 weeks;

9. Adequate organ and bone marrow function, defined as follows:

10. Absolute neutrophil count (ANC) ≥ 1500/mm³ (1.5 × 10^9/L);

11. Platelets ≥ 100,000/mm³ (100 × 10^9/L);

12. Hemoglobin ≥ 9 g/dL (90 g/L);

13. Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) both ≤ 2.5 ×ULN, when liver metastasis is present, ALT or AST both ≤ 5.0 × Upper limit ofnormal value (ULN);

14. Total bilirubin (TBIL) ≤ 1.5 × ULN, when liver metastasis is present, ≤ 3.0 ×ULN;

15. Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 60 mL/min (based on the Cockcroft and Gault formula);

16. All acute toxic reactions from previous anticancer treatments or surgical procedureshave resolved to baseline severity or National Cancer Institute Common TerminologyCriteria for Adverse Events (NCI CTCAE) version 5.0 ≤ Grade 1 (except for alopeciaor other toxicities that the investigator deems have no safety risk to the patient);

17. Women of childbearing age must have a negative serum pregnancy test within 7 daysprior to the start of study medication, and must be willing to use a medicallyrecognized, highly effective contraceptive method (such as intrauterine device,birth control pills, or condoms) during the study period and for one month after thelast administration of the study medication.

Exclusion Criteria:

1. Previous treatment with gemcitabine;

2. Previous treatment with carboplatin for locally recurrent unresectable or metastaticbreast cancer is allowed if it was administered in the adjuvant or neoadjuvantsetting more than 6 months before the first metastatic relapse;

3. Concurrent central nervous system metastases or leptomeningeal disease requiringimmediate radiotherapy or corticosteroid treatment; patients must discontinuesteroid medication for at least 14 days before the first administration of the studydrug. No stereotactic radiosurgery within 7 days or whole brain radiotherapy within 14 days before the first administration of the study drug;

4. Previous receipt of hematopoietic stem cell or bone marrow transplantation;

5. Within 7 days prior to study entry, the patient has received the followingtreatments:

6. Medications known to be strong inhibitors/inducers of CYP3A4;

7. Medications known to significantly prolong the QT interval or cause torsades depointes (antiarrhythmic drugs such as quinidine, disopyramide, procainamide,sotalol, etc.);

8. Within 14 days prior to study entry, the patient has received radiotherapy, orwithin 21 days prior to study entry, the patient has received other investigationaldrug treatment or cytotoxic chemotherapy;

9. Known history of hypersensitivity or suspected allergic symptoms to any component ofBEBT-209, carboplatin, or gemcitabine;

10. In a resting state, the average corrected QT interval (QTc) obtained from 3Electrocardiogram (ECG) examinations is >480msec (corrected using the Fridericiamethod); history of long QT syndrome or confirmed family history of long QTsyndrome; history of clinically significant ventricular arrhythmias, or current useof antiarrhythmic drugs or implantation of defibrillation devices for the treatmentof ventricular arrhythmias;

11. Uncontrolled electrolyte disturbances that may affect the action of QTc-prolongingdrugs (such as hypocalcemia <1.0mmol/L, hypokalemia < lower limit of normal,hypomagnesemia <0.5mmol/L), but re-screening is allowed after interventionaltreatment;

12. History of myocardial infarction, severe/unstable angina, persistent arrhythmias ≥Grade 2 according to NCI CTCAE version 5.0, any grade of atrial fibrillation,coronary/ peripheral artery bypass surgery, symptomatic congestive heart failure,cerebrovascular accident (including transient ischemic attack or symptomaticpulmonary embolism);

13. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or anyupper gastrointestinal surgery including gastrectomy; known malabsorption syndromeor other conditions that may impair the absorption of BEBT-209;

14. Clinically significant active infections, including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiencysyndrome (AIDS)-related diseases. Active hepatitis B is defined as positive forhepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg), and HBV-DNAgreater than the upper limit of normal for the research center. Patients withquantitative HBV DNA greater than the upper limit of normal for the research centerare allowed to receive antiviral treatment before screening to reduce the viral loadto within the normal range, but must continue to receive antiviral treatment forhepatitis B during the trial; active hepatitis C is defined as HCV RNA above thedetection limit;

15. Diabetes with poor blood sugar control as judged by the investigator;

16. Women who plan to conceive again within 5 years without having undergone oocytecryopreservation;

17. Recent or active suicidal ideation or behavior;

18. Currently participating in or about to participate in other interventional clinicaltrials;

19. Other serious acute or chronic medical or psychiatric conditions or laboratory testabnormalities that may increase the risk of participating in the study or the riskassociated with the administration of the study drug, or interfere with the studyresults, and any other conditions that the investigator deems the patient is notsuitable to participate in this study.