Adjuvant Immunotherapy With Anti-PD-1 Monoclonal Antibody Pembrolizumab (MK-3475) Versus Placebo After Complete Resection of High-risk Stage III Melanoma: A Randomized, Double- Blind Phase 3 Trial of the EORTC Melanoma Group
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 1,019
- 主要终点
- Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among All Participants
研究概览
简要总结
This study will assess whether post-surgery therapy with pembrolizumab improves recurrence-free survival (RFS) as compared to placebo for high-risk participants with melanoma (Stage IIIA [> 1 mm metastasis], IIIB and IIIC). The study will also assess whether pembrolizumab improves RFS versus placebo in the subgroup of participants with programmed cell death-ligand 1 (PD-L1)-positive tumor expression. Participants will be stratified for stage of disease and region and then will be randomly assigned to receive either pembrolizumab or placebo as post-surgery therapy in Part 1. In Part 2, participants who experience a disease recurrence are eligible for pembrolizumab treatment (if treated with placebo in Part 1) or pembrolizumab rechallenge (if treated with pembrolizumab in Part 1).
详细描述
As of Amendment 8, enrollment in Part 2 has closed, and an optional pembrolizumab extension study will not be available to participants after study closure.
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
- Double (Participant, Investigator)
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
- •Completely resected Stage III melanoma
- •Tumor tissue available for evaluation of PD-L1 expression
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
- •No prior therapy for melanoma except surgery for primary melanoma lesions (or previously treated with interferon for thick primary melanomas without evidence of lymph node involvement are eligible)
- •Female participants of childbearing potential should be willing to use adequate methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication
- •Male participants should agree to use an adequate method of birth control starting with the first dose of study therapy through 120 days after the last dose of study medication
排除标准
- •Mucosal or ocular melanoma
- •History of (non-infectious) pneumonitis that required steroids or current pneumonitis
- •History of or current interstitial lung disease
- •History of hematologic or primary solid tumor malignancy, unless no evidence of that disease for 5 years
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •Active infection requiring therapy
- •Unstable hyperthyroidism or hypothyroidism
- •Diagnosis of immunodeficiency
- •Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
- •Known history of human immunodeficiency virus (HIV), active Hepatitis B or C
- •Treatment with live vaccine within 30 days prior to the first dose of study medication are not eligible
- •Prior treatment with any anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) monoclonal antibody or anti-programmed cell death receptor 1 (PD-1), anti-programmed cell death receptor ligand 1 (PD-L1), or anti-programmed cell death receptor ligand 2 (PD-L2) agent, or prior participation in any Merck pembrolizumab clinical trial
- •Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study medication
- •Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study medication
- •Participant is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling or child) who is investigational site or Sponsor staff directly involved with this trial without prospective Institutional Review Board approval (by chair or designee) is given
研究组 & 干预措施
Pembrolizumab
In Part 1, participants receive pembrolizumab 200 mg intravenously (IV) as post-surgery therapy every 3 weeks (Q3W) for up to 1 year. During Part 2, participants with documented recurrence may receive optional re-treatment with pembrolizumab Q3W for up to 2 years or disease progression.
干预措施: pembrolizumab (Biological)
Placebo
In Part 1, participants receive placebo IV as post-surgery therapy Q3W. During Part 2, participants with documented recurrence who received placebo in Part 1 may receive optional treatment with pembrolizumab Q3W for up to 2 years or disease progression.
干预措施: placebo (Drug)
结局指标
主要结局
Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among All Participants
时间窗: 6 months
RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants in both treatment arms of Part 1.
Part 1: Percentage of Participants With Recurrence-Free Survival (RFS) At 6 Months Among Participants With PD-L1-positive Tumor Expression
时间窗: 6 months
RFS was defined as the time between the date of randomization and the date of first melanoma recurrence (local, regional, distant metastasis) or death (whatever the cause), whichever occurred first. For participants who remained alive and whose disease had not recurred, RFS was censored on the date of last visit/contact with disease assessments. The percentage of participants with RFS at Month 6 was reported for all participants with PD-L1-positive tumors in both treatment arms of Part 1.
次要结局
- Distant Metastases-free Survival (DMFS) in All Participants(Up to approximately 11 years)
- Distant Metastases-free Survival (DMFS) for Participants With PD-L1-positive Tumor Expression(Up to approximately 11 years)
- Overall Survival (OS) for All Participants(Up to approximately 11 years)
- Overall Survival (OS) for Participants With PD-L1-positive Tumor Expression(Up to approximately 11 years)
- Number of Participants Who Experienced At Least 1 Adverse Event (AE)(Up to 22 months)
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)(Up to 22 months)
- Clearance (CL) of Pembrolizumab(Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.)
- Volume of Distribution (V) of Pembrolizumab(Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.)
- Number of Participants Positive for Anti-Drug Antibodies (ADA) After Pembrolizumab Treatment(Pre-dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and then Day 1 of cycle for every 4 cycles afterwards (up to approximately 16 months). Each cycle is 3 weeks.)