Pre-operative Phase II Trial for Breast Cancer With Nivolumab in Combination With Novel IO (BELLINI Trial)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Pathological complete response rate per cohort,
研究概览
简要总结
To determine whether short-term pre-operative nivolumab either as monotherapy or in combination with low dose doxorubicin or novel IO combinations can induce immune activation in early BC.
详细描述
The investigators aim to test the activity of nivolumab monotherapy in primary breast tumors in a pre-operative window of opportunity trial. As the data of the investigators generated in the TONIC trial (metastatic TNBC) indicate that low dose doxorubicin may 'prime' the tumor microenvironment (TME) resulting in higher response rates on nivolumab, in addition, cohorts for treatment with nivolumab plus low dose doxorubicin will be opened. Given the emerging data on other immunomodulatory strategies, this platform study allows opening additional cohorts for promising novel immune-oncology (IO) drugs for which a strong efficacy signal has been seen without drug safety issues. The investigators will study the TME and systemic host factors with specific emphasis on immunosuppressive processes that can potentially be targeted by novel IO agents to further optimize BC immunotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Signed written informed consent
- •18 years or older at moment of inclusion;
- •Female gender;
- •WHO performance status 0 or 1;
- •Resectable primary breast cancer stage I-III. Nodal status must be examined by ultrasound, fine needle aspiration, sentinel node biopsy, or FDG-PET scan.
- •The tumors must be:
- •at least 10 mm (minimum cT1c) as determined by MRI
- •TNBC defined as ER<10%, HER2-negative OR luminal B defined as ER≥10%, HER2-negative with either Ki67≥20% or PR =<20% OR grade
- •HER2 negative is defined as an IHC score of <2 or 2+ with a negative ISH.
- •For TNBC patients: TIL≥5%
- •For LumB breast cancer patients: TIL≥1%
- •For cohort 3B: N0 status, TN and TIL ≥50%
- •For cohort 4B: N0 status, TNBC and TIL 30-49%
- •For cohort 5B: N0 status, TNBC and TIL ≥50% ● Patients with multifocal/multicentric breast cancer are eligible if triple negative breast cancer histology as well as sufficient TIL percentages (30-49% in cohort 4B, ≥50% in cohort 5B) have been confirmed in all tumor lesions.
排除标准
- •evidence or suspicion of metastatic disease. Evaluation of the presence of distant metastases may include chest X-ray, liver ultrasound, isotope bone-scan, CT-scan of chest and abdomen and/or FDG-PET scan, according to local procedures;
- •evidence of a concurrent contralateral or ipsilateral second primary infiltrating breast cancer. Evaluation of the presence of a concurrent second primary breast cancer may include mammography, breast ultrasound and/or MRI breast;
- •other malignancy except carcinoma in situ and basal-cell and squamous carcinoma of the skin, unless the other malignancy was treated ≥5 years ago with curative intent without the use of chemotherapy or radiotherapy
- •previous radiation therapy or chemotherapy;
- •prior treatment with checkpoint inhibitors (including anti- PD1, -PD-L1, -CTLA-4);
- •concurrent anti-cancer treatment, neoadjuvant therapy or another investigational drug;
研究组 & 干预措施
1A; LumB
Nivolumab
干预措施: Nivolumab (Drug)
1B; TNBC
Nivolumab
干预措施: Nivolumab (Drug)
2A; LUMB
Nivolumab and ipilimumab
干预措施: Nivolumab (Drug)
2A; LUMB
Nivolumab and ipilimumab
干预措施: Ipilimumab (Drug)
2B; TNBC
Nivolumab and ipilimumab
干预措施: Nivolumab (Drug)
2B; TNBC
Nivolumab and ipilimumab
干预措施: Ipilimumab (Drug)
3B; TNBC, High TIL
Nivolumab and ipilimumab
干预措施: Nivolumab (Drug)
3B; TNBC, High TIL
Nivolumab and ipilimumab
干预措施: Ipilimumab (Drug)
结局指标
主要结局
Pathological complete response rate per cohort,
时间窗: up to 3 weeks after surgery, an average of 6 months
number of patients with no residual invasively growing tumor cells detected by microscopic examination in breast and axilla
次要结局
- Incidence of Treatment-Emergent Adverse Events according to NCI Common Toxicity Criteria version 5.0(up to 3 weeks after surgery, an average of 6 months)
- Radiological response rate(At 4 weeks)
- Immune activation after pre-operative nivolumab, either as monotherapy or in combination with ipilimumab or relatlimab or novel IO combinations.(within 6 months after surgery)