An Open-Label, Phase 1, Dose-Escalation Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Intravenous DCR-PDL1 in Adults With Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Change from Baseline in Clinical Chemistry Parameter: Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and Creatine kinase (CK)
研究概览
简要总结
The study will evaluate the safety, tolerability, and pharmacokinetics of intravenous DCR-PDL1 in adults with solid tumors. Participants will be enrolled in one of 4 ascending-dose cohorts. Each treatment cycle will consist of multiple intravenous (IV) doses. Dose escalation decisions will be based on data collected during the dose-limiting toxicity (DLT) period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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 adults, aged greater than or equal to (≥) 18 years.
- •Participants are required to have a documented, locally advanced or metastatic solid tumor malignancy, or non-Hodgkin's lymphoma
- •that is refractory to standard therapy known to provide clinical benefit for their condition OR
- •have demonstrated evidence of disease progression or relapse, via imaging, during or following standard therapy known to provide clinical benefit for their condition, OR
- •have demonstrated intolerance to standard therapy known to provide clinical benefit for their condition. OR
- •for which no standard therapy is available
- •Measurable disease according to RECIST version 1.
- •Malignancy not currently amenable to surgical intervention.
- •ECOG performance status of 0, 1, or 2, and an anticipated life expectancy of ≥ 3 months at the time of signing the informed consent.
- •Other protocol defined inclusion criteria could apply
排除标准
- •Participants with known CNS or leptomeningeal metastases not controlled by prior surgery or radiotherapy, or symptoms suggesting CNS involvement for which treatment is required.
- •Other protocol defined exclusion criteria could apply
研究组 & 干预措施
DCR-PDL1
Participants will receive multiple IV doses of DCR-PDL1 during each treatment cycle.
干预措施: DCR-PDL1 (Drug)
结局指标
主要结局
Change from Baseline in Clinical Chemistry Parameter: Alanine transaminase (ALT), Aspartate transaminase (AST), Gamma-glutamyl transferase (GGT), Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH) and Creatine kinase (CK)
时间窗: Baseline to week 8
Change from Baseline in Clinical Chemistry Parameter: Total protein and Albumin
时间窗: Baseline to week 8
Change from Baseline in Clinical Chemistry Parameter: Total bilirubin, Direct bilirubin, Fasting blood glucose, Creatinine and Blood urea nitrogen (BUN)
时间窗: Baseline to week 8
Change from Baseline in Clinical Chemistry Parameter: Sodium, Chloride and Potassium
时间窗: Baseline to week 8
Incidence and Nature of Adverse Events (AEs)
时间窗: Baseline to week 8
Incidence of Dose-limiting Toxicities (DLTs)
时间窗: Baseline to week 8
Change From Baseline in Vital Signs: Oral, Tympanic, Temporal Artery Temperature
时间窗: Baseline up to week 8
Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position.
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Pressure
时间窗: Baseline up to week 8
Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position.
Change from Baseline in 12-lead Electrocardiogram (ECG): Heart Rate and Pulse Rate
时间窗: Baseline to week 8
Change from Baseline in Hematology Parameter: Hemoglobin
时间窗: Baseline to week 8
Change from Baseline in Hematology Parameter: Hematocrit and Mean corpuscular hemoglobin concentration (MCHC)
时间窗: Baseline to week 8
Change from Baseline in Urinalysis Parameter: Specific Gravity
时间窗: Baseline to week 8
Change from Baseline in Urinalysis Parameter: Blood
时间窗: Baseline to week 8
Change from Baseline in Urinalysis Parameter: Ketones and Nitrite
时间窗: Baseline to week 8
Change from Baseline in Urinalysis Parameter: Leukocyte esterase
时间窗: Baseline to week 8
Change from Baseline in Coagulation Parameter: Fibrinogen
时间窗: Baseline to week 8
Change From Baseline in Vital Signs: Pulse and Respiratory Rate
时间窗: Baseline up to week 8
Vital signs will be measured in a semi-supine (i.e., semi-recumbent) position. Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in 12-lead Electrocardiogram (ECG): QRS intervals
时间窗: Baseline to week 8
ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in Hematology Parameter: Mean corpuscular volume (MCV)
时间窗: Baseline to week 8
Change from Baseline in Hematology Parameter: Mean corpuscular hemoglobin (MCH)
时间窗: Baseline to week 8
Change from Baseline in Coagulation Parameter: International normalized ratio (INR)
时间窗: Baseline to week 8
Change from Baseline in 12-lead Electrocardiogram (ECG): QT intervals
时间窗: Baseline to week 8
ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in 12-lead Electrocardiogram (ECG): QTcF intervals (QT Interval Corrected by the Fridericia Formula)
时间窗: Baseline to week 8
ECG recordings will be made in a semi-supine (i.e., semi-recumbent) position, preceded by at least 5 minutes of rest for the participant in a quiet setting without distractions.
Change from Baseline in Hematology Parameter: Red blood cells, White blood cells, Lymphocytes, Monocytes, Eosinophils, Neutrophils, Basophils and Platelets, Reticulocytes
时间窗: Baseline to week 8
Change from Baseline in Coagulation Parameter: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT)
时间窗: Baseline to week 8
Change from Baseline in Urinalysis Parameter: Glucose, Protein, Bilirubin and Urobilinogen
时间窗: Baseline to week 8
Change from Baseline in Urinalysis Parameter: Potential of Hydrogen (pH) of Urine
时间窗: Baseline to week 8
Number of Participants with Change from Baseline in Physical Examination Findings: Cardiovascular, Respiratory, Gastrointestinal, and Neurological systems
时间窗: Baseline to week 8
A complete physical examination will include, at a minimum, assessments of the cardiovascular, respiratory, gastrointestinal, and neurological systems.
次要结局
- Pharmacokinetic Plasma Concentrations of DCR-PDL1(Pre-dose up to 48 hours post-dose)
- Pharmacokinetic Urine Concentrations of DCR-PDL1(Up to 8 hours post-dose)