A Phase II Clinical Trial of Pembrolizumab (MK-3475) in Subjects With Advanced/Unresectable or Metastatic Urothelial Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 374
- 主要终点
- Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
研究概览
简要总结
This is a study using pembrolizumab (MK-3475, KEYTRUDA®) for first-line treatment of participants with advanced/unresectable (inoperable) or metastatic urothelial cancer who are ineligible for cisplatin-based therapy. The primary study objective is to determine the objective response rate (ORR) in all participants and by programmed cell death ligand 1 (PD-L1) status.
With Amendment 4, once a participant has achieved the study objective or the study has ended, the participant will be discontinued from this study and will be enrolled in an extension study to continue protocol-defined assessments and treatment.
详细描述
Participants receiving pembrolizumab who attain a complete response (CR) may consider stopping trial treatment if they meet criteria for holding therapy. Participants who stop trial treatment after receiving 24 months of trial treatment for reasons other than progressive disease (PD) or intolerability, or participants who attain a CR and stop trial treatment may be eligible for up to one year of retreatment upon experiencing PD.
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 diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies)
- •Ineligible for cisplatin therapy
- •No prior systemic chemotherapy for metastatic disease (adjuvant or neoadjuvant platinum-based chemotherapy with recurrence >12 months since completion of therapy is allowed)
- •Available tissue from a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
- •Measurable disease
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- •Adequate organ function
- •Female participants of childbearing potential have a negative urine or serum pregnancy test; surgically sterile, or willing to use 2 acceptable methods of birth control, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
- •Male participants must be willing to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study treatment
排除标准
- •Disease that is suitable for local therapy administered with curative intent
- •Currently participating or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study treatment
- •Prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks prior to study Day 1 or who has 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 or not recovered from AEs due to a previously administered agent
- •Known additional malignancy that is progressing or requires active treatment excepting 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
- •Active autoimmune disease that has required systemic treatment in past 2 years
- •Evidence of interstitial lung disease or active non-infectious pneumonitis
- •Active infection requiring systemic therapy
- •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 treatment
- •Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor
- •Known human immunodeficiency virus (HIV)
- •Known active Hepatitis B or C
- •Received a live virus vaccine within 30 days of planned start of study treatment
结局指标
主要结局
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%
时间窗: Up to approximately 80.5 months
ORR was determined in participants who had a PD-L1 CPS of ≥10% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%
时间窗: Up to approximately 80.5 months
ORR was determined in participants who had a PD-L1 CPS of ≥1% as measured by immunohistochemistry assay. ORR was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
时间窗: Up to approximately 80.5 months
ORR was determined in all participants and was defined as the percentage of participants who had a confirmed Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). Participants with missing data were considered non-responders. Per protocol, only data generated during the initial course of treatment contributed to the analysis.
次要结局
- Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%(Up to approximately 80.5 months)
- Overall Survival Rate (OS Rate) at Month 12 in All Participants(Month 12)
- Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%(Up to approximately 80.5 months)
- Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%(Up to approximately 80.5 months)
- Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants(Up to approximately 80.5 months)
- Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%(Month 6)
- Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants(Up to approximately 80.5 months)
- Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%(Up to approximately 80.5 months)
- Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%(Up to approximately 80.5 months)
- Progression Free Survival Rate (PFS Rate) at Month 6 in All Participants(Month 6)
- Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%(Month 6)
- Overall Survival (OS) in All Participants(Up to approximately 80.5 months)
- Overall Survival (OS) in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%(Up to approximately 80.5 months)
- Progression Free Survival Rate (PFS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%(Month 6)
- Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%(Month 12)
- Progression Free Survival Rate (PFS Rate) at Month 12 in All Participants(Month 12)
- Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%(Month 12)
- Overall Survival Rate (OS Rate) at Month 6 in All Participants(Month 6)
- Overall Survival Rate (OS Rate) at Month 6 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%(Month 6)
- Overall Survival Rate (OS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥1%(Month 12)
- Programmed Cell Death Ligand 1 (PD-L1) Expression Status(Day 1)
- Progression Free Survival Rate (PFS Rate) at Month 12 in Participants With a Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) of ≥10%(Month 12)
- Number of Participants Who Experienced At Least One Adverse Event (AE)(Up to approximately 80.5 months)
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)(Up to approximately 26 months)