A Phase II Study of Pembrolizumab (MK-3475) as Monotherapy in Subjects With Previously Treated Locally Advanced Unresectable or Metastatic (Stage IV) Mismatched Repair Deficient or Microsatellite Instability-High Colorectal Carcinoma (KEYNOTE-164)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 124
- 主要终点
- Objective Response Rate (ORR) - Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) Assessed by Central Imaging Vendor
研究概览
简要总结
In this study, participants with previously-treated locally-advanced unresectable or metastatic mismatched repair (MMR) deficient or microsatellite instability-high (MSI-H) colorectal carcinoma (CRC) will be treated with pembrolizumab (MK-3475, KEYTRUDA®) monotherapy.
There will be two cohorts in this study: Cohort A and Cohort B. For Cohort A, participants are required to have been previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan. Enrollment into Cohort A has been completed. For Cohort B, participants are required to have been previously treated with at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/ - anti-vascular endothelial growth factor (VEGF)/ epidermal growth factor regulator (EGFR) monoclonal antibody.
The primary hypothesis is that Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors v 1.1 (RECIST 1.1) assessed by central imaging vendor in participants with locally advanced unresectable or metastatic MMR deficient or MSI high CRC is greater than 15%.
详细描述
With protocol amendment 08 (13-Nov-2019), once study participants have achieved the study objective or the study has ended, participants will be discontinued from this study and may be enrolled in a pembrolizumab extension study (NCT03486873) to continue protocol-defined assessments and treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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-proven locally advanced unresectable or metastatic colorectal carcinoma
- •Locally confirmed MMR deficient or MSI-H status
- •Has been previously treated with standard therapies, which must include, for Cohort A, fluoropyrimidine, oxaliplatin, and irinotecan, and for Cohort B, at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/- anti-VEGF/EGFR monoclonal antibody (mAb).
- •Eastern Cooperative Oncology Group performance status of 0 or 1
- •Life expectancy of greater than 3 months
- •Provides an archival or newly obtained (≤60 days prior to first dose of study treatment) tumor tissue sample (Cohort B)
- •At least one measurable lesion
- •Female participants of childbearing potential should be willing to use acceptable methods of contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
- •Male participants should agree to use an adequate method of contraception starting with the first dose of study treatment through 120 days after the last dose of study treatment
- •Adequate organ function
排除标准
- •Currently participating in another study and receiving trial treatment, participated in a study of an investigational agent and received trial treatment within 4 weeks of the first dose of treatment in this study, or used an investigational device within 4 weeks of the first dose of treatment in this study
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- •Known active central nervous system metastases and/or carcinomatous meningitis
- •Prior monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events (AEs) due to a previously administered agent
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
- •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
- •Received a live vaccine within 30 days of planned start of study treatment
- •Known history of human immunodeficiency virus (HIV)
- •Known active Hepatitis B or C
- •Has known history of, or any evidence of interstitial lung disease or active, noninfectious pneumonitis
- •Active infection requiring systemic therapy
- •Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
- •Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment
研究组 & 干预措施
Cohort B - Pembrolizumab 200 mg
Participants were previously treated with at least one line of systemic standard of care therapy: fluoropyrimidine + oxaliplatin or fluoropyrimidine + irinotecan +/ - anti vascular endothelial growth factor (VEGF)/ epidermal growth factor regulator (EGFR) monoclonal antibody. Cohort B participants receive pembrolizumab 200 mg IV on Day 1 Q3W for up to approximately 52 cycles (up to approximately 3 years).
干预措施: Pembrolizumab (Biological)
Cohort A - Pembrolizumab 200 mg
Participants were previously treated with standard therapies, which must include fluoropyrimidine, oxaliplatin, and irinotecan. Cohort A participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of every 3-week cycle (Q3W) for up to approximately 52 cycles (up to approximately 3 years).
干预措施: Pembrolizumab (Biological)
结局指标
主要结局
Objective Response Rate (ORR) - Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) Assessed by Central Imaging Vendor
时间窗: Up to approximately 48 months
Objective response rate was defined as the percentage of the participants in the analysis population who had a complete response (CR) or partial response (PR). Complete Response: disappearance of all target lesions. Partial Response: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Responses were based upon blinded central imaging vendor per RECIST 1.1. The point estimate and 95% confidence interval for the ORR, were provided using an exact binomial distribution (Clopper and Pearson method). Participants without response data were counted as nonresponders. The data cutoff date was 09-SEPT-2019.
次要结局
- Progression-Free Survival (PFS) Per RECIST 1.1 Assessed by Central Imaging Vendor.(Up to approximately 66 months)
- Number of Participants Who Discontinued Study Treatment Due to an AE.(Up to approximately 36 months)
- Disease Control Rate (DCR) Per RECIST 1.1 Assessed by Central Imaging Vendor.(Up to approximately 66 months)
- Number of Participants Who Experienced an Adverse Event (AE).(Up to approximately 66 months)
- Duration of Response (DOR) Per RECIST 1.1 as Assessed by the Central Imaging Vendor(Up to approximately 66 months)
- Overall Survival (OS)(Up to approximately 66 months)