A Phase II, Multicenter, Randomized, Placebo-Controlled, Double-Blind Study of MOXR0916 in Combination With Atezolizumab Versus Atezolizumab Alone in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma Who Are Ineligible for Cisplatin-Based Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 22
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This is a Phase II, multicenter, randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of MOXR0916 in combination with atezolizumab versus placebo and atezolizumab in participants with locally advanced or metastatic urothelial carcinoma (UC) who have not received prior systemic therapy in the locally advanced/metastatic setting and who are ineligible to receive cisplatin-based therapy.
详细描述
The study design has been amended after the decision to prematurely stop patient accrual due to enrollment challenges. As only 5 participants were enrolled, the study blinding will not be maintained, and placebo infusions will not be administered. Patients assigned to the MOXR0916 arm may continue study treatment with the combination of atezolizumab and MOXR0916 or with atezolizumab alone based on a discussion of benefit and risk with the treating investigator.
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
盲法说明
The study design has been amended in that the study blinding will not be maintained.
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
- •Age >= 18 years
- •Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
- •Life expectancy >= 12 weeks
- •Histologically or cytologically confirmed locally advanced or metastatic urothelial carcinoma (UC)
- •Availability of a representative formalin-fixed paraffin-embedded tumor specimen
- •No prior systemic therapy for inoperable locally advanced or metastatic UC
- •Ineligible for cisplatin-based chemotherapy as defined by any one of the following criteria: Impaired renal function (glomerular filtration rate [GFR] > 30 but < 60 milliliter/minute [mL/min]); National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v) 4.0 Grade >= 2 audiometric hearing loss (of 25 Decibel at two contiguous frequencies or more severe); NCI CTCAE v 4.0 Grade >= 2 peripheral neuropathy; ECOG Performance Status of 2
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors v1.1
- •Adequate hematologic and end-organ function
排除标准
- •Significant cardiovascular disease
- •Known clinically significant liver disease
- •Any approved anti-cancer therapy, including chemotherapy or hormonal therapy, within 3 weeks prior to initiation of study treatment
- •Prior treatment with CD137 or OX40 agonists, anti-cytotoxic T-lymphocyte-associated protein (CTLA4), anti-programmed death-1 (PD-1), anti- programmed death-ligand 1 (PD-L1), anti-CD-27, anti- glucocorticoid-induced tumor necrosis factor receptor (GITR) therapeutic antibody or pathway-targeting agents
- •Untreated central nervous system (CNS) metastases or active (progressing or requiring corticosteroids for symptomatic control) CNS metastases
- •Any history of leptomeningeal disease
- •Malignancies other than UC within 5 years prior to Cycle 1, Day 1
- •History of autoimmune disease
- •History of idiopathic pulmonary fibrosis, pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest computed tomography scan
- •Active hepatitis B and C virus infection
- •Positive HIV test at screening
- •Active tuberculosis
- •Prior allogeneic stem cell or solid organ transplantation
研究组 & 干预措施
MOXR0916 plus Atezolizumab
干预措施: MOXR0916 (Drug)
MOXR0916 plus Atezolizumab
干预措施: Atezolizumab (Drug)
Atezolizumab
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: Up to approximately 45 months
PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. Per RECIST v1.1, progressive disease is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline); and an absolute increase of \>= 5 millimeter (mm) in the sum of diameters.
Overall Survival (OS)
时间窗: Up to approximately 45 months
Kaplan Meier estimate of median OS was defined as the time at which half of the participants had died, regardless of the cause of death.
次要结局
- Objective Response (OR) According to RECIST v1.1(Up to approximately 45 months)
- Duration of Objective Response (DOR) According to RECIST v1.1(Up to approximately 45 months)
- Time to Pain Progression, Pain Palliation, and Fatigue Progression as Measured by Participant-Reported Severity According to the M. D. Anderson Symptom Inventory (MDASI)(Up to approximately 45 months)
- Percentage of Participants Reporting Symptom Interference With Daily Living at the Time of Progression According to the MDASI(Up to approximately 45 months)
- Percentage of Participants With Adverse Event (AEs)(Up to approximately 45 months)
- Area Under the Plasma Drug Concentration-time Curve (AUC) of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Maximum Plasma Concentration (Cmax) of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Minimum Plasma Concentration (Cmin) of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Clearance of MOXR0916 and Atezolizumab(Cycle 1 (each cycle is 21 days), Day 1: predose and 30 min. after atezolizumab infusion; Cycle 1, on Days 8 and 15. Cycles 2 4, Day 1: predose and 30 min. after atezolizumab infusion. Cycles 8, 12, and 16: predose)
- Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to MOXR0916 and Atezolizumab(Cycles 1 - 4 and 8, 12, and 16 (each cycle is 21 days), Day 1: predose)