Adebrelimab Plus Apatinib and Etoposide for the Treatment of HER2-Negative Breast Cancer Brain Metastasis: A Phase II Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- CNS-ORR
研究概览
简要总结
Some studies have shown that approximately 15% of patients with advanced hormone receptor (HR) positive breast cancer and 1/3 of triple negative breast cancer will develop brain metastasis. At present, there is no unified drug treatment standard for HER2-negative breast cancer brain metastasis (BCBM). The evidence of single traditional chemotherapy drug as the main treatment of brain metastasis is not sufficient. Some exploratory studies on HER2-negative BCBM have shown that the central nervous system objective response rate (CNS-ORR) of anti-angiogenic drugs combined with chemotherapy is around 55%-80%。 Adebrelimab (a humanized PD-L1 monoclonal antibody) specifically blocks the binding of PD-1 and PD-L1, terminates the immunosuppressive signal produced by T cells, and makes T cells re-recognize tumor cells and kill them, thereby inhibiting tumor growth. In China, Adebelizumab has been approved for using in combination with chemotherapy as a first-line treatment for extensive stage small cell lung cancer. Apatinib (a small molecule VEGFR tyrosine kinase inhibitor) mainly plays an anti-angiogenic effect in the treatment of malignant tumors by inhibiting VEGFR. Apatinib has been approved monotherapy for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma that has progressed or relapsed after at least two systematic chemotherapies, advanced liver cancer that has failed or is intolerable after at least first-line systematic treatment, and first-line treatment in patients with unresectable or metastatic hepatocellular carcinoma combined with camrelizumab.
Due to the lack of effective drug therapy for HER2-negative BCBM, a variety of treatment combinations are still being explored. We hypothesized that adebrelimab plus apatinib and etoposide is an explorable and effective treatment for HER2- negative BCBM.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female, aged ≥18 years
- •Expected survival time ≥3 months.
- •Histologically or cytologically confirmed HER2-negative (IHC 0 or 1+; or IHC 2+ ISH negative) locally recurrent or metastatic disease
- •New brain metastasis or brain metastasis progression after treatment
- •HR+ advanced breast cancer with prior CDK4/6 inhibitor treatment failure or the investigator deems unsuitable for CDK4/6 inhibitors
- •At least one intracranial measurable lesion as defined by RECIST V1.1 criteria；
- •ECOG PS 0-2；
- •Patients must have the ability to swallow oral medication；
- •Prior WBRT, stereotactic radiosurgery, and surgical resection are allowed；
- •Organ function levels are basically normal, and the investigator believes that the study drug can be applied：
- •Voluntarily join this study, sign the informed consent, have good compliance, and are willing to cooperate with follow-up
排除标准
- •Urgent need for local treatment of brain metastasis
- •Immunohistochemistry HER2 positive (IHC 3 or IHC 2 ISH amplification)
- •Previously treated with Apatinib, Avelumab, or VP-16；
- •Severe dysfunction of important organs such as the heart, liver, or kidneys；
- •Inability to swallow, chronic diarrhea, and intestinal obstruction, with multiple factors affecting drug administration and absorption；
- •Participants diagnosed with any other malignant tumor within 5 years before this study, excluding non-melanoma skin cancer that has undergone radical treatment. Basal cell or squamous cell skin cancer or cervical carcinoma in situ and thyroid papillary carcinoma。
- •Patients who allergy to any component of the drugs in this protocol; patients with history of immunodeficiency, including HIV positive, HCV, active hepatitis B, or other acquired or congenital immunodeficiency diseases, or history of organ transplantation
- •History of any cardiac disease, including: (1) arrhythmia requiring medication or clinically significant; (2) myocardial infarction; (3) heart failure; (4) any other cardiac disease judged by the investigator to be unsuitable for participation in this trial, etc.
- •Pregnant or lactation female patients; females of childbearing age with a positive baseline pregnancy test or unwilling to take effective contraceptive measures during the entire trial period；
- •According to the investigator's judgment, there are severe accompanying diseases that endanger the patient's safety or affect the completion of the study (including but not limited to uncontrolled severe hypertension, severe diabetes, active infection, etc.).
研究组 & 干预措施
Adebrelimab+Apatinib+Etoposide
Adebrelimab: 1200mg， ivgtt，administered on the first day of each cycle, with a cycle of 21 days.
Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days.
Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days.
干预措施: Adebrelimab (Drug)
Adebrelimab+Apatinib+Etoposide
Adebrelimab: 1200mg， ivgtt，administered on the first day of each cycle, with a cycle of 21 days.
Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days.
Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days.
干预措施: Apatinib (Drug)
Adebrelimab+Apatinib+Etoposide
Adebrelimab: 1200mg， ivgtt，administered on the first day of each cycle, with a cycle of 21 days.
Apatinib: 250 mg, oral, once daily, continuous use, with a cycle of 21 days.
Etoposide: 50mg/day, oral, administered on days 1-14 of each cycle, with a cycle of 21 days.
干预措施: Etoposide (Drug)
结局指标
主要结局
CNS-ORR
时间窗: 2 months
Central nervous system objective response rate (CNS-ORR), as assessed according to the RANO-BM criteria
次要结局
- CNS-PFS(1 Year)
- Extracranial progression-free survival(2 Years)
- Extracranial objective response rate(2 Years)
- CBR(2 Years)
- OS(3 Years)
- DoR(2 Years)
- Safety(AE recorded from infromed consent to 28 days after treatment completion)
研究者
Wang Tao
Professor
Beijing 302 Hospital