A Study of BEBT-209 Plus Chemotherapy in Patients With Locally Advanced or Metastatic Triple-Negative Breast Cancer
brief summary
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.
detailed description
1. Study Overview This is a randomized, controlled, open-label, multi-center, Phase IIb/III study designed to systematically evaluate the efficacy and safety of BEBT-209 (a selective cyclin-dependent kinase 4/6 \[CDK4/6\] inhibitor) in combination with carboplatin and gemcitabine (CG) compared to CG alone. The study is conducted in patients with locally advanced or metastatic triple-negative breast cancer (TNBC). 2. The trial is structured into two stages:
Phase IIb (Proof of Concept): Primarily focused on assessing the objective response rate (ORR) in approximately 60 participants.
Phase III (Confirmatory): A pivotal stage focused on overall survival (OS) in approximately 386 participants. 3. Scientific Rationale:
Triple-negative breast cancer remains a highly aggressive subtype with limited treatment options once initial therapies fail. BEBT-209 acts as a highly selective CDK4/6 inhibitor. By arresting the cell cycle at the G1 phase, BEBT-209 synchronizes tumor cells, making them more susceptible to chemotherapy-induced DNA damage. Preclinical and early-phase clinical data suggest that BEBT-209 not only enhances the sensitivity of TNBC cells to carboplatin and gemcitabine but also provides a myeloprotective effect, reducing chemotherapy-induced bone marrow suppression. 4. Study Design and Intervention:
Eligible participants are randomly assigned in a 1:1 ratio to either the experimental group or the control group via a central randomization system.
Experimental Group: Participants receive BEBT-209 (150 mg, four times per cycle on Day 1 \[D1\], Day 2 \[D2\], Day 8 \[D8\], and Day 9 \[D9\]) combined with carboplatin (area under the curve \[AUC\] × \[creatinine clearance {CrCl} + 25\]) and gemcitabine (1000 mg/m²). The AUC value is set to 2 mg/mL/min in this study.
Control Group: Participants receive carboplatin (2 \[mg/mL/min\] × \[CrCl {mL/min} + 25\]) and gemcitabine (1000 mg/m²) on Day 1 (D1) and Day 8 (D8) of each 21-day cycle. 5. Stratification Factors:
Phase IIb: Lines of prior therapy (1st-line vs. 2nd-line). Phase III: (1) Lines of prior systemic therapy; (2) Prior programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1, or PD-\[L\]1) inhibitor therapy (yes vs. no); (3) Prior TROP2 antibody-drug conjugate (ADC) therapy (yes vs. no). 6. Assessment and Follow-up:
Tumor response is evaluated every 6 weeks for the first three assessments, then every 9 weeks, and eventually every 12 weeks after one year, based on Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria.
official title
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