A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 495
- 主要终点
- Initial Overall Survival (OS) for All Participants
研究概览
简要总结
This is a study of pembrolizumab (MK-3475, KEYTRUDA®) versus standard treatment (methotrexate, docetaxel or cetuximab) for the treatment of recurrent or metastatic head and neck squamous cell cancer (HNSCC). Participants will be randomly assigned to receive either pembrolizumab or Investigator's choice of standard treatment. The primary study hypothesis is that pembrolizumab treatment prolongs Overall Survival (OS) when compared to standard 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
- •Has histologically- or cytologically-confirmed recurrent disease not amenable to curative treatment with local or systemic therapy, or metastatic (disseminated) head and neck squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
- •Failure of prior platinum therapy
- •Radiographically-measurable disease based on RECIST 1.1
- •Tumor tissue available for PD-L1 biomarker analysis
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
- •Female participants of childbearing potential must be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care
- •Male participants must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after last dose of pembrolizumab or through 120-180 days after the last dose of docetaxel, methotrexate or cetuximab, acccording to local standard of care
- •Exclusion Criteria
- •Disease is suitable for local therapy administered with curative intent
- •Currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks prior to randomization
- •Previously treated with 3 or more systemic regimens given for recurrent and/or metastatic disease
- •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study therapy
- •Not recovered from adverse events due to therapy more than 4 weeks earlier
- •Prior anti-cancer monoclonal antibody (mAb) therapy within 4 weeks prior to study Day 1, or not recovered from adverse events due to agents administered more than 4 weeks earlier
- •Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1
- •Diagnosed and/or treated additional malignancy within 5 years of randomization, with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, and/or curatively-resected in situ cervical and/or breast cancers
- •Active autoimmune disease that has required systemic therapy in the past 2 years with modifying agents, corticosteroids, or immunosuppressive agents
- •Active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Active, non-infectious pneumonitis
- •Active infection requiring systemic therapy
- •Pregnant, 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 trial therapy according to local standard of care
- •Prior therapy with an anti-PD-1 or anti-PD1-L1 or -L2 therapy or previously participated in a Merck pembrolizumab (MK-3475) trial
- •Human immunodeficiency virus (HIV)
- •Hepatitis B or C
- •Live vaccine within 30 days of planned start of study therapy
排除标准
- 未提供
研究组 & 干预措施
Pembroliziumab
Participants will receive pembrolizumab 200 mg intravenous (IV) on Day 1 of each 3-week cycle for up to approximately 24 months. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to approximately 1 additional year at the investigator's discretion.
干预措施: Pembrolizumab (Biological)
Standard Treatment
Participants will receive standard treatment of either methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
干预措施: Methotrexate (Drug)
Standard Treatment
Participants will receive standard treatment of either methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
干预措施: Docetaxel (Drug)
Standard Treatment
Participants will receive standard treatment of either methotrexate 40 mg/m^2 IV (may be escalated to 60 mg/m^2 maximum dose) on Days 1, 8, and 15 of each 3-week cycle; or docetaxel 75 mg/m^2 IV on Day 1 of each 3- week cycle; or cetuximab 400 mg/m^2 IV loading dose on Day 1 and 250 mg/m^2 IV on Days 8 and 15 of Cycle 1, followed by cetuximab 250 mg/m^2 on Days 1, 8, and 15 of each subsequent 3-week cycle.
干预措施: Cetuximab (Biological)
结局指标
主要结局
Initial Overall Survival (OS) for All Participants
时间窗: Up to approximately 2 years
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants.
Updated Final OS for All Participants
时间窗: Up to approximately 2 years
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017.
次要结局
- Duration of Response (DOR) Per RECIST 1.1 in All Participants(Up to approximately 2 years)
- Time to Progression (TTP) Per RECIST 1.1 in All Participants(Up to approximately 2 years)
- OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)(Up to approximately 2 years)
- Objective Response Rate (ORR) Per RECIST 1.1 in All Participants(Up to approximately 2 years)
- Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS(Up to approximately 33 months)
- Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants(Up to approximately 2 years)
- PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS(Up to approximately 2 years)
- ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS(Up to approximately 2 years)
- PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS(Up to approximately 2 years)
- Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants(Up to approximately 33 months)
- DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS(Up to approximately 2 years)
- TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS(Up to approximately 2 years)
- PFS Per Modified RECIST in All Participants(Up to approximately 2 years)
- Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS(Up to approximately 30 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants(Up to approximately 30 months)