A Phase II Clinical Trial of Single Agent Pembrolizumab (MK-3475) in Subjects With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Who Have Failed Platinum and Cetuximab
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 172
- 主要终点
- Number of Participants Experiencing an Adverse Event (AE)
研究概览
简要总结
This is a study of single-agent pembrolizumab (MK-3475) in participants with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who have progressed on platinum-based and cetuximab therapy. The primary study hypothesis is that pembrolizumab will provide a clinically meaningful objective response rate (ORR).
With protocol amendment 05 (02-Jan-2018), once study participants have achieved the study objective 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
- Na
- 干预模型
- Single Group
- 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- or cytologically-confirmed recurrent or metastatic HNSCC of the oral cavity, oropharynx, hypopharynx, and larynx that is considered incurable by local therapies
- •Tumor progression or recurrence within 6 months of the last dose of any number of platinum-based and cetuximab therapy lines in the adjuvant, primary, recurrent, or metastatic setting; must be resistant (not responding) to both platinum and cetuximab
- •Available tissue for biomarker analysis
- •Measurable disease based on RECIST 1.1 as determined by central review
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Adequate organ function
- •Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use 2 adequate methods of contraception starting with the screening visit through 120 days after the last dose of pembrolizumab
- •Male participants with a female partner(s) of childbearing potential must be willing to use 2 adequate methods of contraception from screening through 120 days after the last dose of pembrolizumab
排除标准
- •Disease that is suitable for local therapy administered with curative intent
- •Currently receiving treatment in a study of an investigational agent or using an investigational device <= 4 weeks prior to the first dose of trial medication
- •Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial medication
- •Not recovered from AEs due to a previously administered therapy
- •Known additional malignancy that is progressing or requires active treatment excluding basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cancer
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Has an active autoimmune disease that has required systemic treatment in past 2 years
- •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 medication
- •Human immunodeficiency virus (HIV)
- •Hepatitis B or C
- •Received live vaccine within 30 days of planned start of study therapy
研究组 & 干预措施
Pembrolizumab
Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 24 months
干预措施: pembrolizumab (Biological)
结局指标
主要结局
Number of Participants Experiencing an Adverse Event (AE)
时间窗: Up to 27 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
时间窗: Up to 36 months
ORR was assessed by RECIST 1.1 by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR) defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to \<10 mm or Partial Response (PR) defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants
时间窗: Up to 36 months
Participants with a strong PD-L1 expression status were evaluated for ORR by RECIST 1.1. The expression of PD-L1 was determined by immunohistochemistry (IHC) and strong PD-L1 positive was defined as a PD-L1 tumor proportion score ≥50%. ORR was assessed by performing imaging every 6-9 weeks after the first dose of treatment. ORR was defined as the percentage of participants in the analysis population who had a CR defined as a disappearance of all target lesions with pathological lymph nodes having a reduction in short axis to \<10 mm or PR defined as at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as a reference. Participants with missing data were considered non-responders.
Number of Participants Discontinuing Study Drug Due to an AE
时间窗: Up to 24 months
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of the product, whether or not considered related to the product. Worsening of a preexisting condition temporally associated with the use of the product was also an AE. A serious adverse event (SAE) was an AE that resulted in death, was life threatening, resulted in persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a cancer, was associated with an overdose, or was another important medical event. Per protocol, analysis for this outcome measure was planned to be performed during the initial (first) course of therapy only.
次要结局
- Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants(Up to 76.9 months)
- Overall Survival (OS) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Overall Survival (OS) in All Participants(Up to 76.9 months)
- Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Human Papillomavirus (HPV) Positive Tumors(Up to 76.9 months)
- Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants(Up to 76.9 months)
- Objective Response Rate (ORR) by Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants(Up to 76.9 months)
- Response Duration (DOR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)
- Overall Survival (OS) in Strong Programmed Cell Death Ligand 1 (PD-L1) Positive Participants(Up to 76.9 months)