NOvel Immunotherapy Strategies for Advanced Triple Negative Breast Cancer (TNBC) Patients: TONIC-3 Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- PFS-12
研究概览
简要总结
This is a single center, non-blinded, multi-cohort, non-comparative phase II trial to study the safety and efficacy of tiragolumab with atezolizumab and/or ipilimumab in advanced triple-negative breast cancer.
详细描述
Programmed cell death protein 1 (PD1) -blockade is currently being approved for the neoadjuvant treatment of early TNBC as well as for first-line treatment in combination with chemotherapy for patients with Programmed cell death-ligand 1 (PD-L1) -positive TNBC with metastatic disease. However, response rates are modest, responses are not always durable and PD-L1 is a suboptimal biomarker to select patients for this regimen. Therefore, the overarching goal of this TONIC-3 study is to develop novel immunomodulatory strategies for patients with advanced TNBC making use state-of-the-art research tools to better understand the underlying cancer-immune interactions of this disease
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Metastatic or incurable locally advanced triple negative breast cancer with confirmation of Estrogen receptor (ER) and Human Epidermal growth factor Receptor 2 (HER2) negativity (ER <10%, HER2 IHC 0, 1+ or 2+ with no amplification) on a histological biopsy of a metastatic lesion
- •Patients with PD-L1 negative disease determined using the Combined Positivity Score (CPS<10) (Dako 22C3 IHC) OR previously treated with anti-PD(L)1 in the (neo)adjuvant or metastatic setting (irrespective of PD-L1 status).
- •Metastatic lesion accessible for histological biopsy
- •18 years or older
- •World Health Organisation (WHO) performance status of 0 or 1
- •Maximum of three lines of chemotherapy, including antibody-drug conjugates and Poly-ADP Ribose Polymerase (PARP)-inhibitors, for metastatic disease and with evidence of progression of disease
- •Measurable or evaluable disease according to RECIST1.1
- •Disease Free Interval (defined as time between first diagnosis or locoregional recurrence and first metastasis) longer than 1 year. This does not apply to patients with de novo metastatic disease or patients who did not receive (neo)adjuvant chemotherapy.
- •Adequate bone marrow, kidney and liver function
排除标准
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris
- •Symptomatic brain metastases (subjects with asymptomatic brain metastases are eligible if these are free of progression for at least 4 weeks)
- •History of leptomeningeal disease localization
- •History of having received other anticancer therapies within 2 weeks of start of the study drug
- •History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- •Known hypersensitivy to Chinese hamster ovary cell products or to any component of the atezolizumab or tiragolumab formulation
- •History of immunodeficiency, autoimmune disease, conditions requiring immunosuppression (>10 mg daily prednisone equivalents) or chronic infections.
- •Prior treatment with an anti-CTLA4 or anti-TIGIT antibody.
- •Administration of live vaccine within 30 days of planned start of study therapy.
- •Active other cancer
- •Positive test for hepatitis B, hepatitis C, HIV and/or Epstein Barr virus (EBV)
- •History of uncontrolled serious medical or psychiatric illness
- •Current pregnancy pregnancy or breastfeeding.
研究组 & 干预措施
Tiragolumab and atezolizumab
Tiragolumab 600mg and atezolizumab 1200 mg, both every three weeks
干预措施: Tiragolumab (Drug)
Tiragolumab and atezolizumab
Tiragolumab 600mg and atezolizumab 1200 mg, both every three weeks
干预措施: Atezolizumab (Drug)
Tiragolumab and ipilimumab
Tiragolumab 600mg every 3 weeks and ipilimumab 1mg/kg every 3 weeks for the first 4 cycles
干预措施: Tiragolumab (Drug)
Tiragolumab and ipilimumab
Tiragolumab 600mg every 3 weeks and ipilimumab 1mg/kg every 3 weeks for the first 4 cycles
干预措施: Ipilimumab (Drug)
Tiragolumab, atezolizumab and ipilimumab
Tiragolumab 600mg and atezolizumab 1200mg both every 3 weeks, plus ipilimumab 1mg/kg every 3 weeks for the first 4 cycles
干预措施: Tiragolumab (Drug)
Tiragolumab, atezolizumab and ipilimumab
Tiragolumab 600mg and atezolizumab 1200mg both every 3 weeks, plus ipilimumab 1mg/kg every 3 weeks for the first 4 cycles
干预措施: Atezolizumab (Drug)
Tiragolumab, atezolizumab and ipilimumab
Tiragolumab 600mg and atezolizumab 1200mg both every 3 weeks, plus ipilimumab 1mg/kg every 3 weeks for the first 4 cycles
干预措施: Ipilimumab (Drug)
结局指标
主要结局
PFS-12
时间窗: Assessed at 12 weeks
Progression-free survival rate as measured by the proportion of patients free of progression after 12-weeks of treatment
Incidence of adverse events
时间窗: Assessed until 90 days after the last dose of study treatment or until initiation of new anti-cancer therapy, whichever occurs first
Number of patients with adverse events as measured according to CTCAE v5.0
次要结局
- Progression-free survival(Assessed at week 6, week 12 and every 12 weeks thereafter; median 12 months)
- Clinical benefit rate(Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months)
- Overall survival(Assessed monthly until date of death; median 12 months)
- Objective response rate(Assessed at week 6, week 12 and every 12 weeks thereafter; assessed up to 120 months)