A Multicenter, Randomized, Controlled, Three-Arm, Phase III Study to Evaluate the Safety and Efficacy of Two Dosing Schedules of Pembrolizumab (MK-3475) Compared to Ipilimumab in Patients With Advanced Melanoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 834
- 主要终点
- Progression-free Survival (PFS) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Independent Radiology Plus Oncology Review (IRO)
研究概览
简要总结
This study will evaluate the safety and efficacy of 2 different dosing schedules of pembrolizumab (MK-3475), every 2 weeks (Q2W) and every 3 weeks (Q3W), and compare the 2 schedules to treatment with ipilimumab in ipilimumab-naïve participants with unresectable or metastatic melanoma. The primary hypotheses are that pembrolizumab is superior to ipilimumab with respect to progression-free survival (PFS) and overall survival (OS).
详细描述
Participants assigned to a primary course of pembrolizumab can receive up to 24 months of treatment. Participants with Stable Disease (SD) or better will then proceed to Post Treatment Follow-up. All efficacy and safety analyses will be based on the primary pembrolizumab course.
Participants who experience disease progression during the Post Treatment Follow-up will be eligible for a Second Course of pembrolizumab treatment for up to 1 additional year. With Amendment 05, all Second Course participants will be treated with a fixed dose of pembrolizumab 200 mg Q3W. With Amendment 06, after the study has achieved its key objectives or the study has ended, participants will be discontinued from this study and enrolled in an extension study to continue protocol-defined assessments and treatment.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically-confirmed diagnosis of unresectable Stage III or metastatic melanoma not amenable to local therapy (excluding uveal or ocular melanoma)
- •At least one measurable lesion
- •No prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (first line) or one prior systemic treatment (excluding adjuvant or neoadjuvant therapy) for melanoma (second line)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Archived tissue sample or new biopsy sample
- •Female participants of childbearing potential must agree to use effective contraception from Visit 1 to 120 days after the last dose of study drug; male participants must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days after the last dose of study drug
- •Exclusion criteria:
- •Prior treatment with ipilimumab or other anti-cytotoxic T-Lymphocyte Antigen 4 (CTLA-4) agent or any anti-programmed cell death (PD-1 or PD-L2) agent
- •Chemotherapy, radioactive, or biological cancer therapy within four weeks prior to the first dose of study drug, or not recovered from adverse events caused by cancer therapeutics administered more than four weeks earlier
- •Currently participating or has participated in a study of an investigational agent or using an investigational device within 30 days of the first dose of study drug
- •Expected to require any other form of systemic or localized antineoplastic therapy while on study
- •On any systemic steroid therapy within one week before the planned date for first dose of randomized treatment or on any other form of immunosuppressive medication
- •History of a malignancy (other than the disease under treatment in the study) within 5 years prior to first study drug administration, excluding adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other in situ cancers.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases are eligible
- •Severe hypersensitivity reaction to treatment with another monoclonal antibody
- •Active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents
- •Active infection requiring systemic therapy
- •Known history of Human Immunodeficiency Virus (HIV)
- •Known history of or positive for Hepatitis B or C
- •Known psychiatric or substance abuse disorder
- •Regular user (including recreational use) of illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)
- •Pregnant or breastfeeding, or expecting to conceive, or father children within the projected duration of the study
- •Received a live vaccine within 30 days prior to first dose of study drug
排除标准
- 未提供
结局指标
主要结局
Progression-free Survival (PFS) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Independent Radiology Plus Oncology Review (IRO)
时间窗: Up to approximately 12 months (through first pre-specified statistical analysis cut-off date of 03-Sep-2014)
PFS was defined as the time from randomization to the first documented disease progression, based on blinded Independent Radiology plus Oncology review (IRO) using RECIST 1.1, or death due to any cause, whichever occurred first. Disease progression was defined as a 20% or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of new lesions. The primary analysis of PFS was performed at the time of the first protocol pre-specified statistical analysis, with data cut-off of 03-Sep-2014.
Percentage of Participants With Overall Survival (OS) at 12 Months
时间窗: Month 12
OS was defined as the time from randomization to death due to any cause. The percentage of participants with OS (OS rate) at 12 months was reported for each arm. The reported percentage was estimated using a product-limit (Kaplan-Meier) method for censored data; data were censored at the date of cut-off. The primary analysis of OS was performed at the time of the second protocol pre-specified statistical analysis, with data cut-off of 03-Mar-2015.
次要结局
- Objective Response Rate (ORR) According to RECIST 1.1 as Assessed by IRO(Up to approximately 12 months (through first pre-specified statistical analysis cut-off date of 03-Sep-2014))