Randomized Phase II Trial of Anti-Lag-3 and Anti-PD-1 Blockade vs. SOC in Patients With Recurrent Glioblastoma
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 184
- 试验地点
- 595
- 主要终点
- Overall survival (OS)
研究概览
简要总结
This phase II trial compares the safety, side effects and effectiveness of anti-lag-3 (relatlimab) and anti-PD-1 blockade (nivolumab) to standard of care lomustine for the treatment of patients with glioblastoma that has come back after a period of improvement (recurrent). Relatlimab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Lomustine is a chemotherapy drug and in a class of medications called alkylating agents. It damages the cell's deoxyribonucleic acid and may kill tumor cells. Giving relatlimab and nivolumab may be safe, tolerable, and/or effective compared to standard of care lomustine in treating patients with recurrent glioblastoma.
详细描述
PRIMARY OBJECTIVE:
I. To compare the restricted mean survival time (RMST) for overall survival (OS) between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care chloroethylcyclohexylnitrosourea (CCNU) (lomustine).
SECONDARY OBJECTIVES:
I. To compare the 12-month OS rates between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).
II. To compare the restricted mean survival times for progression-free survival (PFS) between patients receiving the combination of relatlimab (BMS-986016) and nivolumab versus patients receiving standard of care CCNU (lomustine).
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
- •Histologically-proven glioblastoma (World Health Organization [WHO] 2021 criteria)
- •Progressive or recurrent disease per Response Assessment in Neuro-Oncology (RANO) criteria
- •No IDH mutation (IDH1 R132H negative by immunohistochemistry [IHC] or sequencing)
- •Patients must be in first recurrence of glioblastoma following radiation therapy and temozolomide
- •No prior therapies except radiation, surgery, temozolomide, Tumor Treating Fields (TTFields), and/or Gliadel wafers (placed during the first surgery at diagnosis of glioblastoma multiforme [GBM]). Prior radiation therapy, TTFields, or placement of Gliadel wafers must be completed at least 2 weeks prior to registration. Prior temozolomide must be completed at least 3 weeks prior to registration
- •No prior use of nivolumab or other anti-PD1 agents
- •Patients must be neurologically stable off corticosteroids for at least 5 days prior to registration
- •Age: ≥ 18 years
- •Karnofsky Performance Status: ≥ 60% (i.e. patient must be able to care for themselves with occasional help from others)
- •Absolute lymphocyte count (ALC): ≥ 1000/mm^3
- •Absolute neutrophil count (ANC): ≥ 1500/mm^3
- •Platelet count: ≥ 100,000/mm^3
- •Hemoglobin: ≥ 9.0 g/dL
- •Activated partial thromboplastin time (APTT) or partial thromboplastin time (PTT): ≤ 1.5 x upper limit of normal (ULN)
- •Total bilirubin: < 2.0 x ULN (Except for patients with Gilbert's syndrome, who must have direct bilirubin < 2.0 x ULN)
- •Aspartate aminotransferase (AST) / alanine aminotransferase (ALT): < 3.0 x ULN
- •Calculated (calc.) creatinine clearance (CrCl): ≥ 50 mL/min
- •Calculated by Cockcroft-Gault equation
- •Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown and an agent that has known genotoxic, mutagenic and teratogenic effects. Therefore, for women of childbearing potential only, a negative pregnancy test done within 14 days prior to registration is required
- •Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
- •No active brain metastases or leptomeningeal disease
- •HIV: HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
- •Hepatitis B: For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- •Hepatitis C: Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- •No known medical condition causing an inability to swallow oral formulations of agents
- •No current symptomatic pulmonary disease
- •No autoimmune disorders that require systemic treatment (except hyperthyroidism or diabetes mellitus)
排除标准
- 未提供
研究组 & 干预措施
Arm I (nivolumab, relatlimab)
Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Biospecimen Collection (Procedure)
Arm I (nivolumab, relatlimab)
Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (nivolumab, relatlimab)
Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Biopsy Procedure (Procedure)
Arm I (nivolumab, relatlimab)
Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Nivolumab (Biological)
Arm I (nivolumab, relatlimab)
Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Relatlimab (Biological)
Arm II (lomustine)
Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Lomustine (Drug)
Arm II (lomustine)
Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Surgical Procedure (Procedure)
Arm II (lomustine)
Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (nivolumab, relatlimab)
Patients receive nivolumab IV over 30 minutes followed by relatlimab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Surgical Procedure (Procedure)
Arm II (lomustine)
Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Biopsy Procedure (Procedure)
Arm II (lomustine)
Patients receive lomustine PO on day 1 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo surgery or biopsy, MRI, and blood sample collection throughout study.
干预措施: Biospecimen Collection (Procedure)
结局指标
主要结局
Overall survival (OS)
时间窗: From randomization until death due to any cause, assessed at 30 months
The comparison of OS between the arms will be made with respect to restricted mean survival time (RMST) at 30 months. The RMST difference between arms will be determined as a point estimate with a corresponding 90% confidence interval (CI).
OS rate
时间窗: From randomization until death due to any cause, assessed at 12 months
The OS rate between the 2 arms will be compared using a chi-square test. The point estimate and corresponding 90% CI will be generated for the difference in proportion.
次要结局
- Radiographic response(Up to 5 years)
- Incidence of adverse events (AEs)(Up to 5 years)
- Progression-free survival(From randomization until confirmed disease progression as assessed by the treating physician or death due to any cause, whichever occurs first, assessed up to 5 years)
- Radiographic response(Up to 5 years)
- Incidence of adverse events (AEs)(Up to 5 years)