Bone Marrow Protection, Safety, Efficacy of Trilaciclib and Eribulin in Locally Advanced or Metastatic TNBC(Triple-negative Breast Cancer)

Four randomized, double-blind clinical trials of treacilil in patients with small cell lung cancer (SCLC) confirmed that Trilaciclib administration in combination with chemotherapy prevented or mitigated chemotherapy-induced myelosuppression.Among them, the G1T28-05 study showed that the administration of Trilaciclib before first-line chemotherapy (carboplatin combined with etoposide) could reduce the duration of severe neutropenia in the first cycle from 4 days to 0 days, and the incidence of severe neutropenia from 49.1% to 1.9%.As the world's first drug designed to reduce chemotherapy-induced myelosuppression by protecting HSPCs, Trilaciclib has demonstrated a significant ability to prevent chemotherapy-mediated multicellular lineage myelosuppression in patients with ES-SCLC.In February 2021, the U.S. Food and Drug Administration (FDA) approved Trilaciclib (COSELA™) to reduce the incidence of chemotherapy-induced myelodepression in adult patients with extensive stage small cell lung cancer prior to receiving a platinum-containing/etoposide regimen or topotecan regimen.

Based on the evidence that Trilaciclib has been approved by the FDA to reduce the incidence of chemotherapy-induced myelopathic depression in adult patients with extensive stage small cell lung cancer prior to receipt of a platinum-containing/etoposide regimen or topotecan regimen, there is encouraging patient outcome improvement observed in study G1T28-04.This Phase II clinical trial was designed to confirm the bone marrow protection and efficacy and safety of Trilaciclib in patients with locally advanced/metastatic TNBC who had previously received at least two chemotherapy regimes prior to treatment with Eribulin.

Inclusion criteria

• ≥18 years old , no limitation of gender;
• locally advanced or metastatic triple-negative breast cancer;
• have received at least two prior chemotherapy regimens(The recurrence of the last adjuvant chemotherapy is counted one line within 12 months after surgery);
• At least one measurable lesion according to RECIST version 1.1;
• The laboratory tests meet the following criteria:

Hemoglobin: ≥ 100 g / L (female), 110g / L (male) Neutrophil count : ≥2×10^9/L Platelet count: ≥100×10^9/L Creatinine：≤15mg / L or creatinine clearance (CrCl) ≥60 mL/min (Cockcroft-Gault formula); Total bilirubin：≤1.5× upper limit of normal (ULN) Alutamate aminotransferase (ALT) and glutamate aminotransferase (AST)≤ 3 ×ULN or 5 ×ULN (for patients with liver metastases) Albumin: ≥ 30 g / L;

• Eastern Cooperative Oncology Group (ECOG) score [0-1] points;
• The expected survival period is ≥3 months;
• During the screening period, all female with potential fertility must have negative serum pregnancy tests and reliable contraception after signing the informed consent form until 3 months after the last dose;
• Comprehend and voluntarily sign the informed consent form;

Exclusion criteria

• Diagnosed other malignant disease besides breast cancerwithin 5 years before the first dose (excluding radical skin basal cell carcinoma, skin squamous epithelial carcinoma, and / or radical resection);
• Main organ function not good enough;
• Bone marrow invasion;
• Require combined chemotherapy other than Eribulin;
• Stroke or cardiovascular and cerebrovascular events within 6 months before enrollment;
• QTcF > 480 msec ( screening period) and QTcF> 500 msec for patients with ventricular pacemaker implantation;
• Previous hematopoietic stem cell or bone marrow transplantation;
• Previous G-CSF treatment in the last 2 weeks;
• Allergic to the study drug or the ingredients;
• Any other situation where the researcher considers the patient not suitable to participate in this study.