A Phase II Study of Atezolizumab, Vinorelbine and Weekly Cyclophosphamide as T-cell Activators in First Line Metastatic Triple Negative Breast Cancer Patients Pre-treated With Anti-PD-L1/PD-1
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 4
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
Triple-negative breast cancer (TNBC) is among the most aggressive and lethal types of breast cancer, and currently available therapies have an unsatisfactory impact on patients' survival.
The primary aim of this clinical trial is to evaluate efficacy in terms of Overall Response Rate (ORR) of atezolizumab plus cyclophosphamide and vinorelbine in first line patients with unresectable locally advanced or metastatic TNBC patients, previously treated with anti-programmed cell death ligand-1 (PD-L1) or anti-programmed cell death-1 (PD-1) - containing regimens, in the neoadjuvant/adjuvant setting.
详细描述
TNBC is among the most aggressive and lethal types of breast cancer, and currently available therapies have an unsatisfactory impact on patients' survival.
The association of checkpoint inhibitors (CIs) such as anti-PD-L1 with chemotherapy has shown some encouraging results in randomized clinical trials enrolling TNBC patients either in the early (neo-adjuvant) or in the advanced/metastatic setting, but there has been no clear evidence of what should be considered the best chemotherapy backbone to be associated with CIs.
What could be considered the most promising combinatorial regimen of chemotherapy plus anti-PDL1 was defined using two complementary TNBC models at the preclinical level. The present phase II study will investigate overall response rate (ORR) as primary endpoint in first line metastatic TNBC patients treated with this investigational combination comprising atezolizumab (A) Vinorelbine (V), and Cyclophosphamide (C).
Secondary objectives will investigate duration of response (DOR), progression-free survival (PFS) and overall survival (OS) and the safety of the study regimen.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form
- •Patients with locally advanced or metastatic, histologically documented TNBC (absence of human epidermal growth factor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PR] expression) PD-L1+ (Immune Cell >1% using Ventana SP142 assay), not amenable to surgical therapy
- •Locally advanced or metastatic TNBC, who have received an anti-PD-1/PD-L1 containing regimen in the neoadjuvant/adjuvant setting
- •No prior chemotherapy or targeted systemic therapy (including endocrine therapy) or immunotherapy for inoperable locally advanced or metastatic TNBC
- •Tissue accessible for biopsies
- •Expected survival of > 3 months
- •Female or male subject ≥18 years
- •Have measurable/evaluable metastatic disease (RECIST 1.1 criteria)
- •Performance status 0-1 on Eastern Cooperative Oncology Group Performance Status (ECOG PS)
- •Demonstrate adequate organ (kidney, liver) function
排除标准
- •Patients with de novo metastatic TNBC OR those who have received 1 or more chemotherapy or targeted systemic therapy (including endocrine therapy) or immunotherapy regimens for advanced disease
- •Immunodeficiency or systemic steroid therapy/immunosuppressive therapy within 7 days prior to study entry
- •Known history of active Bacillus Tuberculosis (TBC)
- •Hypersensitivity to anti- PD-L1 antibodies or its excipients
- •Active autoimmune disease
- •Known history of non-infectious pneumonitis
- •Active infection requiring systemic therapy
- •Known history of Human Immunodeficiency Virus (HIV)
- •Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative])
- •Live vaccine within 30 days
- •Bone or brain metastases
研究组 & 干预措施
Atezolizumab plus Cyclophosphamide and Vinorelbine
Atezolizumab 840 mg intravenous (IV) on Days 1 and 15 of every 28-day cycle in combination with Cyclophosphamide 300 mg/m2 IV on Days 1 ,8,15, 21 of every 28-day cycle and Vinorelbine 30 mg per os (PO) on Days 1, 3, 5 every week of every 28-day cycle
干预措施: Atezolizumab in combination with Cyclophosphamide and Vinorelbine (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 30 months
Rate of subjects who achieve either a confirmed Complete Response (CR) or Partial Response (PR)
次要结局
- Progression-free survival (PFS)(30 months)
- Overall survival (OS)(30 months)
- Duration on response (DoR)(30 months)