NCT03489369已完成1 期
A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym022 (Anti-LAG-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 15
- 试验地点
- 3
- 主要终点
- Assessment of Treatment Related Adverse Events (AEs).
研究概览
简要总结
This is the first study to test Sym022 in humans. The primary purpose of this study is to see if Sym022 is safe and tolerable for patients with locally advanced/unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available.
详细描述
This study will evaluate the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym022, an anti-lymphocyte activation gene 3 (anti-LAG-3) monoclonal antibody (mAb). The goal is to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym022 when administered once every 2 weeks (Q2W) by intravenous (IV) infusion to patient cohorts with locally advanced/ unresectable or metastatic solid tumor malignancies or lymphomas that are refractory to available therapy or for which no standard therapy is available. If an MTD is not identified, a maximum administered dose (MAD) will be determined. Sym022 will be given to patients in escalating dose cohorts; each patient will be given one fixed dose level.
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 patients, ≥ 18 years of age at the time of obtaining informed consent.
- •Documented (histologically- or cytologically-proven) solid tumor malignancy that is locally advanced or metastatic; patients with documented lymphomas.
- •Malignancy (solid tumor or lymphoma) that is currently not amenable to surgical intervention due to either medical contraindications or nonresectability of the tumor.
- •Refractory to or intolerant of existing therapy(ies) known to provide clinical benefit.
- •Measurable or non-measurable disease according to RECIST v1.1 or RECIL
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or
- •Not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 6 months after the last dose of study drug.
排除标准
- •Women who are pregnant or lactating, or intending to become pregnant before, during, or within 6 months after the last dose of study drug. Women of childbearing potential (WOCBP) and fertile men with WOCBP partner(s), not using and not willing to use a highly effective method of contraception.
- •Known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression, patients with any of the above not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required.
- •Hematologic malignancies other than lymphomas.
- •Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE) within 4 weeks prior to Cycle 1/Day 1 (C1/D1) unless adequately treated and considered stable
- •Active uncontrolled bleeding or a known bleeding diathesis
- •Clinically significant cardiovascular disease or condition
- •Significant pulmonary disease or condition
- •Current or recent (within 6 months) significant gastrointestinal (GI) disease or condition.
- •An active, known, or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome, requiring systemic steroids or other immunosuppressive medications.
- •History of organ transplantation (e.g. stem cell or solid organ transplant)
- •History of significant toxicities associated with previous administration of immune checkpoint inhibitors that necessitated permanent discontinuation of that therapy
- •Patients with unresolved > Grade 1 toxicity associated with any prior antineoplastic therapy, with exceptions.
- •Inadequate recovery from any prior surgical procedure, or having undergone any major surgical procedure within 4 weeks prior to C1/D
- •Known history of human immunodeficiency virus (HIV) or known active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV).
- •Other Inhibitors of LAG-3
- •Any antineoplastic agent for the primary malignancy (standard or investigational) without delayed toxicity within 4 weeks or 5 plasma half-lives, whichever is shortest, prior to first administration of study drug and during study
- •Any other investigational treatments within 4 weeks prior to and during study
- •Radiotherapy for target lesions within 4 weeks prior to first administration of study drug unless PD has been documented in the lesion following treatment, and during study.
- •Radiotherapy for non-target lesions within 1 week prior to first administration of study drug
- •Immunosuppressive or systemic hormonal therapy
- •Prophylactic use of hematopoietic growth factors within 1 week prior to first administration of study drug and during Cycle 1 of study
研究组 & 干预措施
Sym022
Experimental
Sym022 will be administered at up to 4 planned dose levels.
干预措施: Sym022 (Drug)
结局指标
主要结局
Assessment of Treatment Related Adverse Events (AEs).
时间窗: 19 months
Assess the safety, tolerability and dose-limiting toxicities of Sym022 on a Q2W schedule to establish the MTD and/or RP2D.
次要结局
- Evaluation of Objective Response (OR) or Stable Disease (SD).(13 months)
- Area Under the Concentration-time Curve in a Dosing Interval (AUC).(19 months)
- Trough Concentration (Ctrough)(0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week))
- Terminal Elimination Half-life (T½)(0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week))
- Evaluation of the Immunogenicity of Sym022.(19 months)
- Time to Progression (TTP) of Disease.(13 months)
- Maximum Concentration (Cmax)(0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week))
- Time to Reach Maximum Concentration (Tmax)(0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week))
- Clearance (CL)(0, 2, 4, 8, 24, 48, 168 hours and 336 hours as administered Q2W (every second week))
研究者
研究点 (3)
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