An Open-label, Randomized, Phase 1 Safety and Pharmacokinetic Study of Enfortumab Vedotin (ASG-22CE) in Japanese Patients With Locally Advanced or Metastatic Urothelial Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 8
- 主要终点
- PK parameter for ADC: AUC0-7
研究概览
简要总结
The objective of this study is to assess the safety, tolerability and pharmacokinetics of enfortumab vedotin (ASG-22CE) when administered intravenously to Japanese subjects with locally advanced or metastatic urothelial carcinoma. This study will also assess the immunogenicity as defined by the incidence of anti-drug antibody (ADA) and anti-tumor activity of enfortumab vedotin (ASG-22CE) when administered intravenously to Japanese subjects with locally advanced or metastatic urothelial carcinoma.
详细描述
All subjects will receive a single 30 minute intravenous (IV) infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.
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
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must have histologically confirmed, locally advanced (TNM classification T3b and any N; or T and N2-3) or metastatic Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
- •Subject must be able to submit a tumor tissue samples for Nectin-4 expression analysis at central laboratory.
- •Subject must have failed at least one prior chemotherapy regimen for advanced disease. Urothelial and bladder cancer subjects are not required to have failed prior chemotherapy regimen if considered unfit for cisplatin-based chemotherapy.
- •Subject must have measurable disease according to Response Evaluation Criteria in Solid Tumor (RECIST) (version 1.1).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
排除标准
- •Preexisting sensory neuropathy Grade ≥
- •Preexisting motor neuropathy Grade ≥
- •Uncontrolled central nervous system metastasis that requires active treatment.
- •Any anticancer therapy within 14 days prior to the first dose of study drug.
- •Subjects with pre-existing immunotherapy-related adverse events requiring high doses of systemic steroids are not eligible.
研究组 & 干预措施
Arm A: Enfortumab vedotin 1.0 mg/kg
All subjects assigned will receive a single 30 minute intravenous infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.
干预措施: Enfortumab vedotin (Drug)
Arm B: Enfortumab vedotin 1.25 mg/kg
All subjects assigned will receive a single 30 minute intravenous infusion of enfortumab vedotin (ASG-22CE) once weekly for 3 weeks of every 4 weeks (i.e., on Days 1, 8, and 15). A cycle is 28 days.
干预措施: Enfortumab vedotin (Drug)
结局指标
主要结局
PK parameter for ADC: AUC0-7
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
AUC0-7 will be derived from the PK blood samples collected.
PK parameter for ADC: Ctrough
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Ctrough will be derived from the PK blood samples collected.
PK parameter for ADC: Cmax
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Cmax will be derived from the PK blood samples collected.
PK parameter for MMAE: Cmax
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Cmax will be derived from the PK blood samples collected.
Pharmacokinetics (PK) parameter for Monomethyl Auristatin E (MMAE): CEOI
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
CEOI will be derived from the PK blood samples collected.
PK parameter for ADC: Tmax
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Tmax will be derived from the PK blood samples collected.
PK parameter for MMAE: Tmax
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Tmax will be derived from the PK blood samples collected.
Safety assessed by incidence of adverse events
时间窗: Up to 12 months
Adverse events will be coded using MedDRA. Adverse events collection begins after signing informed consent and collected until 28 days after the last dose of study drug.
Safety assessed by laboratory tests: Urinalysis
时间窗: Up to 12 months
Descriptive statistics will be used to summarize results.
Safety assessed by electrocardiogram (ECG)
时间窗: Up to 12 months
Before measurement of ECGs, the participant should be resting in a supine position for at least 5 minutes. The investigator will assess the ECG charts as "normal", "abnormal (not clinically significant)" or "abnormal (clinically significant)". "Abnormal (not clinically significant)" and "abnormal (clinically significant)" findings will be recorded.
PK parameter for MMAE: Ctrough
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Ctrough will be derived from the PK blood samples collected.
PK parameter for TAb: Time to maximum concentration (Tmax)
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Tmax will be derived from the PK blood samples collected.
Safety assessed by laboratory tests: Biochemistry
时间窗: Up to 12 months
Descriptive statistics will be used to summarize results.
Number of participants with vital sign abnormalities and/or adverse events
时间窗: Up to 12 months
Number of participants with potentially clinically significant vital sign values.
Pharmacokinetics (PK) parameter for total antibody (TAb): Concentration at the end of infusion (CEOI)
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
CEOI will be derived from the PK blood samples collected.
Pharmacokinetics (PK) parameter for antibody drug conjugate (ADC): CEOI
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
CEOI will be derived from the PK blood samples collected.
PK parameter for TAb: Maximum observed concentration (Cmax)
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Cmax will be derived from the PK blood samples collected.
PK parameter for MMAE: AUC0-7
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
AUC0-7 will be derived from the PK blood samples collected.
PK parameter for ADC: t1/2
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
T1/2 will be derived from the PK blood samples collected.
PK parameter for TAb: Partial area under the serum concentration-time curve after first dose and as appropriate (AUC0-7)
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
AUC0-7 will be derived from the PK blood samples collected.
Safety assessed by laboratory tests: Hematology
时间窗: Up to 12 months
Descriptive statistics will be used to summarize results.
Safety assessed by laboratory tests: Coagulation studies
时间窗: Up to 12 months
Descriptive statistics will be used to summarize results.
PK parameter for TAb: Trough concentration (Ctrough)
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
Ctrough will be derived from the PK blood samples collected.
PK parameter for TAb: Terminal or apparent terminal half-life (t1/2)
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
T1/2 will be derived from the PK blood samples collected.
PK parameter for MMAE: t1/2
时间窗: Days 1-4, 8, 15-18, 22 of Cycle 1, Day 1 of Cycle 2 and 3, and subsequent cycles up to an average of 12 months
T1/2 will be derived from the PK blood samples collected.
次要结局
- Overall Response Rate(Up to 12 months)
- Disease Control Rate(Up to 12 months)
- Incidence of Anti-Drug Antibody (ADA)(Up to 12 months)