A Phase 1a/b Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of OMP-313M32 Administered as a Single Agent or in Combination With Nivolumab to Subjects With Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 33
- 试验地点
- 5
- 主要终点
- Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate the safety and tolerability of OMP-31M32 as a single agent or in combination with nivolumab. OMP-313M32 is an experimental anti-TIGIT antibody that was developed to block TIGIT from binding PVR allowing the body's T-cells to destroy cancer cells.
详细描述
This is an open-label, Phase 1a/b dose escalation study of OMP-31M32 administered as a single agent or in combination with nivolumab to evaluate the safety, tolerability pharmacokinetics, and pharmacodynamics in patients with locally advanced or metastatic solid tumors. This study consists of a screening period, a treatment period and a post-treatment follow-up period in which patients will be followed for survival for up to 2 years. Subjects will be enrolled in two stages in the Phase 1a (dose escalation and expansion) and one stage in the Phase 1b (dose escalation).
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
- •Histologic documentation of locally advanced, recurrent or metastatic solid malignancy that has progressed and standard therapy has been ineffective or intolerable. Phase 1b subjects must also have experienced disease progression after treatment with an anti PD-1 or PDL-1 agent.
- •Ability to understand the willingness and to sign a written informed consent document
- •Age >/= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy >/=12 weeks
- •Measurable disease per response evaluation criteria in solid tumors.
- •Adequate hematologic and organ function
- •For women of childbearing potential and men with partners of childbearing potential, agreement (by patient and/or partner) to use two effective forms of contraception from study entry through at least 6 months after the termination visit.
排除标准
- •Anti-cancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks or 5 half lives, whichever is shorter, prior to initiation of study treatment
- •Active autoimmune disease or a history of severe autoimmune disease or syndrome
- •History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
- •Inability to comply with study and follow-up procedures.
- •Pregnancy, lactation, or breastfeeding women.
- •Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina.
- •Known clinically significant liver disease,
- •Major surgical procedure within 28 days prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study.
- •Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications.
研究组 & 干预措施
OMP-313M32
Intravenous (in the vein) infusions of OMP-313M32 as a single agent
干预措施: OMP-313M32 (Drug)
OMP-313M32 and Nivolumab
Intravenous (in the vein) infusions of OMP-313M32 in combination with nivolumab
干预措施: OMP-313M32 (Drug)
OMP-313M32 and Nivolumab
Intravenous (in the vein) infusions of OMP-313M32 in combination with nivolumab
干预措施: Nivolumab (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs)
时间窗: Subjects will be assessed for DLTs through the end of the first cycle (Days 1-29)
The Maximum tolerated dose (MTD) or maximum administered dose (MAD) will be determined in patients treated with OMP-313M32 in combination with nivolumab
Incidence of treatment emergent adverse events
时间窗: up to approximately 2 years
Percentage of patients with adverse events
次要结局
- Pharmacokinetic Outcome Measures (AUC) - Phase 1a(1st dose and 4th dose: pre-dose, post-infusion, and 1, 3, 7 and 10 days. All other doses: pre-dose, 15 minutes and 7 days post-infusion. PK sample will be taken at treatment termination and every 4 wks for 12 wks.)
- Pharmacokinetic Outcome Measures (AUC) - Phase 1b(1st dose and 4th dose: pre-dose and 15 minutes post-infusion. All other doses: pre-dose. PK sample will be taken at treatment termination and every 4 wks for 12 wks.)
- Pharmacokinetic Outcome Measures (T1/2) - Phase 1a(1st dose and 4th dose: pre-dose, post-infusion, and 1, 3, 7 and 10 days. All other doses: pre-dose, 15 minutes and 7 days post-infusion. PK sample will be taken at treatment termination and every 4 wks for 12 wks.)
- Pharmacokinetic Outcome Measures (T1/2) - Phase 1b(1st dose and 4th dose: pre-dose and 15 minutes post-infusion. All other doses, pre-dose.PK sample will be taken at treatment termination and every 4 wks for 12 wks.)
- Immunogenicity of OMP-313M32(up to approximately 2 years)
- Objective Response(up to approximately 2 years)
- Progression-free survival(approximately 2 years)