A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym023 (Anti-TIM-3) in Patients With Advanced Solid Tumor Malignancies or Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 4
- 主要终点
- Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria.
研究概览
简要总结
This was the first study to test Sym023 in humans. The primary purpose of this study was to see if Sym023 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 evaluated the preliminary safety, tolerability, and dose-limiting toxicities (DLTs) of Sym023, a recombinant, fully human, anti-T-cell immunoglobulin and mucin-domain containing-3 (anti-TIM-3) monoclonal antibody (mAb). The goal was to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of Sym023 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 was not identified, a maximum administered dose (MAD) was to be determined. Sym023 was given to patients in escalating dose cohorts; each patient was given one fixed dose level.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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 ocular disease or condition, including history of autoimmune or inflammatory disorder.
- •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 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).
研究组 & 干预措施
Sym023 0.03 mg/kg
Sym023 was administered at a dose of 0.03 mg/kg by intravenous infusion
干预措施: Sym023 (Drug)
Sym023 0.1 mg/kg
Sym023 was administered at a dose of 0.1 mg/kg by intravenous infusion
干预措施: Sym023 (Drug)
Sym023 0.3 mg/kg
Sym023 was administered at a dose of 0.3 mg/kg by intravenous infusion
干预措施: Sym023 (Drug)
Sym023 1.0 mg/kg
Sym023 was administered at a dose of 1.0 mg/kg by intravenous infusion
干预措施: Sym023 (Drug)
Sym023 3.0 mg/kg
Sym023 was administered at a dose of 3.0 mg/kg by intravenous infusion
干预措施: Sym023 (Drug)
Sym023 10.0 mg/kg
Sym023 was administered at a dose of 10.0 mg/kg by intravenous infusion
干预措施: Sym023 (Drug)
Sym023 20.0 mg/kg
Sym023 was administered at a dose of 20.0 mg/kg by intravenous infusion
干预措施: Sym023 (Drug)
结局指标
主要结局
Assessment of Treatment Emergent Adverse Events (AEs) Meeting Dose-limiting Toxicity (DLT) Criteria.
时间窗: 28 days
Assess the safety and tolerability of Sym023 on a Q2W (once every 2 weeks) schedule to establish the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D). Assessment based on the occurrence of AEs meeting DLT criteria measured during Cycle 1. The MTD was to be determined by those DLTs that occurred during C1 in either more than 1 patient in a 3 to 6 patient cohort or ≥33.3% of patients in the event of an expanded 7 to 12 patient cohort. One patient in the 10.0 mg/kg dose cohort was not evaluable for MTD as she did not complete C1 for a reason other than drug toxicity (i.e., discontinuation after 1 dose due to patient withdrawal of consent). However, this patient was included in the evaluation of other outcomes.
次要结局
- Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIL 2017.(24 months)
- Evaluation of the Immunogenicity of Sym023.(Baseline up to 6-months follow-up, approximately 1 year)
- Evaluation of Objective Response (OR) or Stable Disease (SD) by RECIST v1.1(24 months)
- Trough Concentration (Ctrough)(From before the start of the infusion to 168 hours after the end of the infusion)
- Evaluation of Objective Response (OR) or Stable Disease (SD) by iRECIST(24 months)
- Time to Progression (TTP) of Disease.(24 months)
- Maximum Concentration (Cmax)(From before the start of the infusion to 168 hours after the end of the infusion)
- Time to Reach Maximum Concentration (Tmax)(From before the start of the infusion to 168 hours after the end of the infusion)
- Area Under the Concentration-time Curve in a Dosing Interval (AUC).(From before the start of the infusion to 168 hours after the end of the infusion)
- Clearance (CL)(From before the start of the infusion to 168 hours after the end of the infusion)
- Terminal Elimination Half-life (T½)(From before the start of the infusion to 168 hours after the end of the infusion)