A Phase III, Randomized, Open-Label, Multicenter, Global Study of Volrustomig (MEDI5752) in Combination With Carboplatin Plus Pemetrexed Versus Platinum Plus Pemetrexed or Nivolumab Plus Ipilimumab in Participants With Unresectable Pleural Mesothelioma (eVOLVE-Meso)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 863
- 试验地点
- 152
- 主要终点
- Overall Survival (OS) in experimental arm relative to comparator arm
研究概览
简要总结
This is a phase III, randomized, open-label, multicenter, global study to determine the efficacy and safety of Volrustomig (MEDI5752) + Carboplatin + Pemetrexed vs the investigator's choice of platinum + Pemetrexed or Nivolumab + Ipilimumab in participants with unresectable pleural mesothelioma.
详细描述
Adult patients with histologically proven diagnosis of pleural mesothelioma with advanced unresectable disease are eligible to be enrolled. Patients will be randomized 1:1 to receive Volrustomig (MEDI5752) + Carboplatin + Pemetrexed or the investigator's choice of platinum+Pemetrexed or Nivolumab+Ipilimumab, based on their histology.
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
- Single (Outcomes Assessor)
盲法说明
This is an open-label study for the personnel at study sites; the specific treatment to be taken by a participant will be assigned using an Interactive Response Technology/Randomization and Trial Supply Management. To maintain the integrity of the study, AstraZeneca personnel directly involved in the study conduct will not undertake or have access to efficacy data aggregated by treatment arm prior to final data readout for the primary endpoint.
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
- •Participant must be ≥ 18 years at the time of screening
- •Histologically proven diagnosis of pleural mesothelioma with known histology (epithelioid vs. non-epithelioid)
- •Advanced unresectable disease that cannot be treated with curative surgery (with or without chemotherapy)
- •WHO/ECOG performance status of 0 or 1 with no deterioration (that is, ECOG PS>1) over the previous 2 weeks prior to day of first dosing
- •Has measurable disease per modified RECIST1.1
- •Has adequate bone marrow reserve and organ function at baseline
排除标准
- •As judged by the investigator, any condition that would interfere with evaluation of the investigational product or interpretation of participant safety or study results.
- •Active or prior documented autoimmune or inflammatory disorders
- •History of another primary malignancy with exceptions.
- •Uncontrolled intercurrent illness
- •Tuberculosis, hepatitis B (HBV) or hepatitis C (HCV), human immunodeficiency virus (HIV) infection that is not well controlled
- •Any concurrent chemotherapy, radiotherapy, investigational, biologic, or hormonal therapy for cancer treatment
- •Untreated or progressive CNS metastatic disease
研究组 & 干预措施
Volrustomig + Carboplatin + pemetrexed
Volrustomig in combination with carboplatin plus pemetrexed
干预措施: Pemetrexed (Drug)
Investigator's choice of standard care
The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
干预措施: Cisplatin (Drug)
Investigator's choice of standard care
The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
干预措施: Nivolumab (Drug)
Investigator's choice of standard care
The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
干预措施: Ipilimumab (Drug)
Volrustomig + Carboplatin + pemetrexed
Volrustomig in combination with carboplatin plus pemetrexed
干预措施: Volrustomig (Drug)
Volrustomig + Carboplatin + pemetrexed
Volrustomig in combination with carboplatin plus pemetrexed
干预措施: Carboplatin (Drug)
Investigator's choice of standard care
The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
干预措施: Pemetrexed (Drug)
Investigator's choice of standard care
The investigator's choice of nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy for participants with epithelioid histology, and nivolumab plus ipilumab for participants with non-epithelioid histology.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Overall Survival (OS) in experimental arm relative to comparator arm
时间窗: up to approximately 61 months
OS is defined as the time from randomization until the date of death due to any cause.
次要结局
- Overall Survival (OS)(up to approximately 61 months)
- Progression Free Survival (PFS)(up to approximately 61 months)
- Landmark OS(12, 18, 24, 36 months)
- Landmark PFS(6, 12, 18, 24 months)
- Overall Response Rate (ORR)(up to approximately 61 months)
- Duration of Response (DoR)(up to approximately 61 months)
- PFS2(up to approximately 61 months)
- Patient-reported physical functioning(up to approximately 61 months.)
- Disease-related symptoms using EORTC IL305 (Q1)(Up to approximately 61 months.)
- Disease-related symptoms using PRO-CTCAE (Q1, 5, 6, 9)(Up to approximately 61 months)
- Patient-reported role functioning using EORTC QLQ-C30 RF subscale (IL305 Q2 3)(up to approximately 61 months)
- Patient-reported HRQoL (Health-related Quality of Life) using EORTC QLQ-C30 HRQoL subscale (IL305 Q7-8)(Up to approximately 61 months)
- Immunogenicity of volrustomig(up to approximately 61 months)
- Incidence of Adverse Events (AEs) AEs graded by CTCAE version 5.0(Up to approximately 61 months)
- Area under the curve (AUC)(Up to approximately 61 months)
- Maximum plasma concentration of the drug (Cmax)(Up to approximately 61 months)
- The time taken to reach the maximum concentration (Tmax)(Up to approximately 61 months)