A Single-arm, Open-label, Multicenter Study of Enfortumab Vedotin (ASG-22CE) for Treatment of Patients With Locally Advanced or Metastatic Urothelial Cancer Who Previously Received Immune Checkpoint Inhibitor (CPI) Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 219
- 试验地点
- 81
- 主要终点
- Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
研究概览
简要总结
This is a study that will test how an experimental drug (enfortumab vedotin) affects patients with cancer of the urinary system (urothelial cancer). This type of cancer includes cancer of the bladder, renal pelvis, ureter or urethra that has spread to nearby tissues or to other areas of the body.
This clinical trial will enroll patients who were previously treated with a kind of anticancer drug called an immune checkpoint inhibitor (CPI). Some CPIs have been approved for the treatment of urothelial cancer.
This study will test if the cancer shrinks with treatment. This study will also look at the side effects of the drug. A side effect is a response to a drug that is not part of the treatment effect.
Patients who sign up for this trial must also fall into one of these categories:
- Patients have already received treatment with platinum-containing chemotherapy
- Patients have never received platinum-containing treatment and are not eligible for treatment with cisplatin.
详细描述
Japan Pharmaceuticals and Medical Devices Agency (PMDA) has approved enfortumab vedotin (Padcev) for the treatment of advanced urothelial cancer. The study will continue as a post marketing study in Japan.
This study will examine the safety and anticancer activity of enfortumab vedotin given intravenously to patients with locally advanced or metastatic urothelial cancer who previously received a CPI and either previously received platinum-containing chemotherapy (Cohort 1) or are platinum-naïve and cisplatin-ineligible (Cohort 2). Patients who received platinum in the adjuvant/neoadjuvant setting and did not progress within 12 months of completion will be considered platinum-naïve. Approximately 100 patients are expected to be enrolled in each cohort. The primary goal of the study is to determine the confirmed ORR of enfortumab vedotin.
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
- •Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
- •Metastatic disease or locally advanced disease that is not resectable.
- •Must have received prior treatment with a CPI in the locally advanced or metastatic urothelial cancer setting. A CPI is defined as a programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor. Patients who received CPI therapy in the neoadjuvant/adjuvant setting and had recurrent or progressive disease either during therapy or within 3 months of therapy completion are eligible.
- •Must either have prior treatment with platinum-containing chemotherapy (Cohort 1) or be platinum-naïve and ineligible for treatment with cisplatin at time of enrollment (Cohort 2).
- •Must have had progression or recurrence of urothelial cancer during or following receipt of most recent therapy.
- •Tumor tissue samples must be available for submission to the sponsor prior to study treatment.
- •Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1).
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status score of ≤1 for Cohort 1 or ≤2 for Cohort
- •Anticipated life expectancy of ≥3 months as assessed by the investigator.
排除标准
- •Ongoing sensory or motor neuropathy Grade ≥
- •Active central nervous system (CNS) metastases.
- •Immunotherapy related myocarditis, colitis, uveitis, or pneumonitis.
- •Prior enrollment in an enfortumab vedotin study or prior treatment with other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
- •Uncontrolled tumor-related pain or impending spinal cord compression.
研究组 & 干预措施
Enfortumab vedotin
Enfortumab vedotin on days 1, 8 and 15 every 28 days
干预措施: Enfortumab vedotin (Drug)
结局指标
主要结局
Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR)
时间窗: Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27)
ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). CR is defined as disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR is defined as a \>=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.
次要结局
- DCR16 Per Investigator Assessment(Up to Week 16)
- PK Parameter for Free MMAE: AUC (Plasma)(AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose))
- PK Parameter for Enfortumab Vedotin: Area Under Concentration-Time Curve (AUC) (Serum)(AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose))
- Duration of Objective Response (DOR) Per BICR(Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27))
- Progression-Free Survival (PFS) Per BICR(Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27))
- ORR Per Investigator Assessment(Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27))
- DOR Per Investigator Assessment(Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27))
- PFS Per Investigator Assessment(Cohort 1: median follow-up time: 10.15 months (range 0.49, 16.46); Cohort 2: median follow up time: 13.4 months (range 0.33 to 29.27))
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Hematology)(The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months])
- Number of Participants With Treatment-Emergent Laboratory Abnormalities (Serum Chemistry)(The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months])
- Incidence of Antitherapeutic Antibody (ATA)(The median duration of treatment was 4.60 months for Cohort 1 [full range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [full range: 0.3, 24.6 months])
- Disease Control Rate at 16 Weeks (DCR16) Per BICR(Up to Week 16)
- Overall Survival (OS): Primary Analysis(Cohort 1 median follow-up time: 28.4 months [range 0.49, 32.62]; Cohort 2 median follow up time: 13.4 months [range 0.33 to 29.27])
- Number of Participants With Adverse Events (AEs): Primary Analysis(The median duration of treatment was 4.60 months for Cohort 1 [range: 0.5, 29.4 months] and 5.98 months for Cohort 2 [range: 0.3, 24.6 months])
- Pharmacokinetics (PK) Parameter for Enfortumab Vedotin: Maximum Concentration (Cmax) (Serum)(Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22)
- PK Parameter for Enfortumab Vedotin: Time to Maximum Concentration (Tmax) (Serum)(Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22)
- PK Parameter for Free Monomethyl Auristatin E (MMAE): Cmax (Plasma)(Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22)
- Overall Survival (OS): Final Analysis(Cohort 1: median follow-up: 61.0 months (range 59.63, 62.36); Cohort 2: median follow-up time: 45.8 months (range 44.91 to 48.95))
- PK Parameter for Free MMAE: Tmax (Plasma)(Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22)
- PK Parameter for TAb: AUC (Serum)(AUC0-7 was assessed (in cycles 1 and 2) based on concentration data from Day 1 to Day 8 (pre dose) and AUC0-14 was assessed based on data from D15 (pre dose) to D29 (pre-dose))
- PK Parameter for Total Antibody (TAb): Cmax (Serum)(Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22)
- PK Parameter for TAb: Tmax (Serum)(Collected during cycle 1 and 2 of treatment (each cycle=28 days) at Day 1 pre-dose and end of infusion, Day 3, Day 8 pre-dose and end of infusion, Day 15 pre-dose and end of infusion, Day 17, and Day 22)
- Number of Participants With Adverse Events (AEs): Final Analysis(Cohort 1: median treatment duration time: 4.60 months (range 0.5, 43.0); Cohort 2: median treatment duration time: 5.98 months (range 0.3 to 25.8))