BEBT-209 combined with chemotherapy for advanced triple-negative breast cancer

A Phase II Study of BEBT-209 in Combination With Carboplatin and Gemcitabine for the Treatment of Advanced Triple-Negative Breast Cancer

This study is testing if a new drug called BEBT-209, when combined with chemotherapy, can help people with advanced triple-negative breast cancer feel better and improve their treatment outcomes.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: BeBetter Med Inc (industry)
• Drugs / interventions: chemotherapy
• Locations: 2 sites (Guangzhou, Guangdong and 1 other locations)
• Trial ID: NCT06685796 on ClinicalTrials.gov

What this trial studies

This multicenter, open-label Phase II clinical study evaluates the safety and efficacy of BEBT-209 capsules in combination with carboplatin and gemcitabine for patients with advanced triple-negative breast cancer. The study consists of three cohorts, with patients randomly assigned to each cohort to assess tolerability and clinical benefit. Initial enrollment focuses on safety assessment, and if tolerable, the study will expand to include more subjects. The treatment regimen varies across cohorts, with specific dosing schedules for BEBT-209 and chemotherapy.

Who should consider this trial

Good fit: Ideal candidates are females aged 18 and older with confirmed advanced triple-negative breast cancer who have received 1-2 lines of prior systemic treatment.

Not a fit: Patients with hormone receptor-positive or HER2-positive breast cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced triple-negative breast cancer.

How similar studies have performed: While there have been studies exploring similar combinations, the specific use of BEBT-209 in this context is novel.

Eligibility criteria

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 metastatic breast cancer by pathological biopsy;
4. Estrogen and progesterone receptor immunohistochemical assessment of tumor tissue is negative (defined as \<1% nuclear staining), and HER2 is negative (i.e., no overexpression, including local immunohistochemical assessment \[0 or 1+\], or immunohistochemical assessment \[2+\] with negative in situ hybridization testing);
5. The subject has previously received 1-2 lines of systemic treatment (if progression within 12 months after the last treatment of adjuvant/new adjuvant, it can be considered as one line of treatment);
6. At least one measurable lesion in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria;
7. Eastern Cooperative Oncology Group (ECOG) score of 0-1 , and no decline in physical performance in the past two weeks;
8. Life expectancy of at least 12 weeks;
9. Adequate organ and bone marrow function, defined as follows:

   1. Absolute neutrophil count (ANC) ≥ 1500/mm³ (1.5 × 10\^9/L);
   2. Platelets ≥ 100,000/mm³ (100 × 10\^9/L);
   3. Hemoglobin ≥ 9 g/dL (90 g/L);
   4. Alanine Aminotransferase (ALT) or Aspartate Transaminase (AST) both ≤ 2.5 × ULN, when liver metastasis is present, ALT or AST both ≤ 5.0 × Upper limit of normal value (ULN);
   5. Total bilirubin (TBIL) ≤ 1.5 × ULN, when liver metastasis is present, ≤ 3.0 × ULN;
   6. Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 60 mL/min (based on the Cockcroft and Gault formula);
10. All acute toxic reactions from previous anticancer treatments or surgical procedures have resolved to baseline severity or National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 ≤ Grade 1 (except for alopecia or other toxicities that the investigator deems have no safety risk to the patient);
11. Women of childbearing age must have a negative serum pregnancy test within 7 days prior to the start of study medication, and must be willing to use a medically recognized, highly effective contraceptive method (such as intrauterine device, birth control pills, or condoms) during the study period and for one month after the last administration of the study medication.

Exclusion Criteria:

1. Previous treatment with gemcitabine;
2. Previous treatment with carboplatin for locally recurrent unresectable or metastatic breast cancer is allowed if it was administered in the adjuvant or neoadjuvant setting more than 6 months before the first metastatic relapse;
3. Concurrent central nervous system metastases or leptomeningeal disease requiring immediate radiotherapy or corticosteroid treatment; patients must discontinue steroid medication for at least 14 days before the first administration of the study drug. 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 following treatments:

   1. Medications known to be strong inhibitors/inducers of CYP3A4;
   2. Medications known to significantly prolong the QT interval or cause torsades de pointes (antiarrhythmic drugs such as quinidine, disopyramide, procainamide, sotalol, etc.);
6. Within 14 days prior to study entry, the patient has received radiotherapy, or within 21 days prior to study entry, the patient has received other investigational drug treatment or cytotoxic chemotherapy;
7. Known history of hypersensitivity or suspected allergic symptoms to any component of BEBT-209, carboplatin, or gemcitabine;
8. In a resting state, the average corrected QT interval (QTc) obtained from 3 Electrocardiogram (ECG) examinations is \>480msec (corrected using the Fridericia method); history of long QT syndrome or confirmed family history of long QT syndrome; history of clinically significant ventricular arrhythmias, or current use of antiarrhythmic drugs or implantation of defibrillation devices for the treatment of ventricular arrhythmias;
9. Uncontrolled electrolyte disturbances that may affect the action of QTc-prolonging drugs (such as hypocalcemia \<1.0mmol/L, hypokalemia \< lower limit of normal, hypomagnesemia \<0.5mmol/L), but re-screening is allowed after interventional treatment;
10. 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 symptomatic pulmonary embolism);
11. Active inflammatory bowel disease or chronic diarrhea, short bowel syndrome, or any upper gastrointestinal surgery including gastrectomy; known malabsorption syndrome or other conditions that may impair the absorption of BEBT-209;
12. Clinically significant active infections, including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related diseases. Active hepatitis B is defined as positive for hepatitis B surface antigen (HBsAg) or hepatitis B e antigen (HBeAg), and HBV-DNA greater than the upper limit of normal for the research center. Patients with quantitative HBV DNA greater than the upper limit of normal for the research center are allowed to receive antiviral treatment before screening to reduce the viral load to within the normal range, but must continue to receive antiviral treatment for hepatitis B during the trial; active hepatitis C is defined as HCV RNA above the detection limit;
13. Diabetes with poor blood sugar control as judged by the investigator;
14. Women who plan to conceive again within 5 years without having undergone oocyte cryopreservation;
15. Recent or active suicidal ideation or behavior;
16. Currently participating in or about to participate in other interventional clinical trials;
17. Other serious acute or chronic medical or psychiatric conditions or laboratory test abnormalities that may increase the risk of participating in the study or the risk associated with the administration of the study drug, or interfere with the study results, and any other conditions that the investigator deems the patient is not suitable to participate in this study.

Where this trial is running

Guangzhou, Guangdong and 1 other locations

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (RECRUITING)
• Hunan Cancer Hospital — Changsha, Hunan, China (RECRUITING)

Study contacts

• Principal investigator: Quchang Ouyang, Phd — Hunan Cancer Hospital
• Study coordinator: Kegang Jiang, Master

Conditions: Advanced Triple-Negative Breast Cancer, BEBT-209, Safety, Efficacy, In Combination With Chemotherapy