A Phase II With 2 Parallel Cohorts Clinical Trial Targeting Estrogen Receptor Negative or PAM50 Non-luminal Disease With Atezolizumab in Combination With Trastuzumab and Vinorelbine in HER2-positive Advanced/Metastatic Breast Cancer - ATREZZO Study
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 55
- 试验地点
- 15
- 主要终点
- Overall Response rate
研究概览
简要总结
Immune checkpoint inhibitors given in monotherapy in advanced breast cancer have shown modest benefit in first-line, but very limited efficacy in later lines. Thus, combination therapies are needed.
Response following anti-PD1/PD-L1 monotherapy is associated with large survival benefit in the advanced setting.
Previous studies of the intrinsic subtypes have shown that Basal-like and HER2-E are associated with higher expression of immune-related genes or higher infiltration of stromal tumor infiltrating lymphocytes compared to the luminal subtypes. Immune infiltration in BC is associated with chemo/antiHER2 responsiveness and potentially benefit from anti-PD-1/PD-L1 inhibitors.
In addition, one emerging biomarker of response to anti-PD-1 therapy is the tumor mutational burden (I.e. the total number of mutations per coding area of a tumor genome). The HER2-E and Basal-like profiles have been associated with high mutational burden.
A range of studies have been initiated including several phase II/III studies evaluating atezolizumab in combination with different chemotherapeutic compounds routinely used in breast cancer, but none with predefined biomarker beyond the expression of PD-L1 by IHC
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
- •Male or female (Premenopausal or postmenopausal women)
- •ECOG 0 to 2
- •Histologically confirmed adenocarcinoma of the breast, metastatic or unresectable locally advanced.
- •All patients must have received at least trastuzumab and other anti-HER2 ADCs (including but not limited to T-DM1).
- •Measurable disease according to RECIST 1.1 criteria.
- •Adequate organ function
- •Baseline LVEF ≥50%
- •Participants with asymptomatic brain metastases are eligible.
排除标准
- •Treatment with any investigational anticancer drug within 14 days of the start of study treatment.
- •Patient has received Vinorelbine or any other vinca alkaloids previously immediately prior to initiate study treatment.
- •History of other malignant tumors in the past 3 years
- •Known or suspected leptomeningeal disease (LMD)/ poorly controlled (> 1/week) generalized or complex partial seizures, or manifest neurologic progression due to brain metastases.
- •Symptomatic hypercalcemia requiring treatment with bisphosphonates in the 14 days prior to inclusion
- •Cardiopulmonary dysfunction
- •Any other severe, uncontrolled
- •Major surgery in the 28 days prior to enrolment
- •Infection with HIV or active Hepatitis B and/or Hepatitis C.
- •History of trastuzumab intolerance, including grade 3-4 infusion reaction or hypersensitivity.
- •Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
- •History of autoimmune disease,
- •Prior allogeneic stem cell or solid organ transplantation
- •History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan. (Note: History of radiation pneumonitis in the radiation field [fibrosis] is permitted.)
- •Active tuberculosis
- •Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment
- •Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or immune checkpoint targeting agents
- •Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin [IL]-2) within 4 weeks or five half-lives of the drug prior to enrolment
- •Treatment with systemic immunosuppressive medications within 2 weeks prior to enrolment, or anticipated requirement for systemic immunosuppressive medications during the trial.
研究组 & 干预措施
Atezolizumab in combination with Trastuzumab and Vinorelbine
干预措施: Atezolizumab + Trastuzumab + Vinorelbine (Drug)
结局指标
主要结局
Overall Response rate
时间窗: until disease progression or up to 2 years after treatment ends
the proportion of patients with best overall response of complete response (CR) or partial response (PR), as per local investigator´s assessment and according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria
次要结局
- Overall Response rate in PD-L1+ patients(until disease progression or up to 2 years after treatment ends)
- Progression free survival(24 weeks)
- Overall Response rate in patients with brain metastases at baseline(Until disease progression or up to 2 years after treatment ends)
- Clinical Benefit in patients with brain metastases at baseline(24 weeks)
- Clinical Benefit(24 weeks)
- Time to response(24 weeks)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](until end of treatment / through study completion, an average of 1 year)
- Overal survival in patients with brain metastases at baseline(Until analysis data cutoff, 2 years)
- Overal survival(Until analysis data cutoff, 2 years)
- Duration of response(24 weeks)
- Progression free survival in patients with brain metastases at baseline(24 weeks)