Trilaciclib in Patients With Early-Stage HR-negative Breast Cancer Receiving Adjuvant Chemotherapy

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Prior neoadjuvant therapy (including chemotherapy, targeted therapy, immunotherapy, or radiotherapy);

• History of other malignancy within 5 years prior to first dose, except basal cell carcinoma and cervical carcinoma in situ;

• Any T4 or N2 or known N3 or M1 breast cancer;

• Subjects who cannot receive or tolerate postoperative chemotherapy for various reasons;

• Heart disease ineligible for epirubicin, docetaxel, trastuzumab/pertuzumab:

  • Any documented history of myocardial infarction, congestive heart failure
  • Angina pectoris requiring antianginal medication
  • Grade 3 or 4 cardiac arrhythmia (NCI CTCAEv5.0)
  • Clinically significant valvular heart disease;
  • Poorly controlled hypertension (systolic blood pressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg)

• Known history of hypersensitivity to the drug components of this protocol;

• Any other condition that, in the opinion of the investigator, would make the patient inappropriate for participation in this study.