A Prospective, Multi-cohort, Exploratory Phase II Study of Trilaciclib Combined With Standard Chemotherapy in The Adjuvant Treatment of Hormone Receptor (HR) Negative Breast Cancer
The goal of this multicenter, two-cohort, exploratory clinical trial is to evaluate patients with early stage hormone receptor-negative breast cancer receiving standard adjuvant chemotherapy after surgery. The main question it aims to answer is: • The efficacy and safety of trilaciclib administered before standard adjuvant chemotherapy regimen using the incidence of grade 3/4 neutropenia as the primary efficacy endpoint. Participants will divide into two treatment cohorts according to molecular typing type: * Cohort A will be planned to include post-operative triple-negative breast cancer(TNBC) patients with lymph node positive or tumor \> 2 cm treated with trilaciclib combined with epirubicin and cyclophosphamide followed by weekly paclitaxel; * Cohort B will be planned to include HER2-positive/HR-negative breast cancer patients with axillary node positive or tumor \> 2 cm treated with trilaciclib combined with docetaxel, carboplatin and trastuzumab with or without pertuzumab.
• age ≥ 18 years;
• breast cancer meets the following criteria:
‣ Histologically or cytologically confirmed and adequately resected non-metastatic primary invasive breast cancer;
⁃ Cohort A only: ER, PR negative (\< 1% nuclear staining as assessed by immunohistochemistry \[IHC\]), HER2 negative (HER2/CEP17 ratio \< 2.0 or mean HER2 gene copy number \< 4 signals/nucleus detected by IHC 0 or 1 + or in situ hybridization \[ISH\]); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were HR negative/HER2 negative.
⁃ Cohort B only: ER, PR negative (\< 1% nuclear staining as assessed by immunohistochemistry \[IHC\]); HER2 positive: HER2/CEP17 ratio ≥ 2.0 or HER2 gene copy number ≥ 4 signals/nucleus detected by IHC 3 + and ISH; HER2 gene copy number ≥ 6 signals/nucleus detected by IHC 3 + or 2 + and ISH); patients with concurrent bilateral invasive disease met the inclusion criteria if both lesions were HR negative/HER2 positive.
⁃ Subjects must have positive lymph nodes or tumors \> 2 cm;
⁃ The interval between radical surgery and the first dose ≤ 60 days;
• Eastern Cooperative Oncology Group (ECOG) performance score 0-1;
• have appropriate organ function, meet the following criteria: (1) have appropriate bone marrow function: Hb ≥ 100 g/L (no ESA and blood transfusion within 14 days before the first dose); absolute neutrophil count (ANC) ≥ 2 × 10\^9/L (no G-CSF within 14 days before the first dose); platelet count ≥ 100 × 10\^9/L (no rhTPO/rhIL-11 and platelet transfusion within 14 days before the first dose); (2) appropriate liver and kidney function: alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN), aspartate aminotransferase (AST) ≤ 2.5 × ULN, total bilirubin (TBIL) ≤ 1.5 × ULN, serum creatinine ≤ 1.5 × ULN, endogenous creatinine clearance \> 50 ml/min (Cockcroft-Gault formula); (3) appropriate cardiac function: left ventricular ejection fraction (LVEF) ≥ 55%;
• Non-hematologic toxicities from prior surgical procedures recovered to ≤ Grade 1 or baseline (except alopecia);
• Females of childbearing potential agree to practice reliable contraception during the clinical trial and have a negative serum or urine pregnancy test within 7 days prior to dosing;
• Voluntarily join this study and sign informed consent, have good compliance and are willing to cooperate with follow-up.