Clinical Trials List
Protocol NumberMK3475-052
NCT Number(ClinicalTrials.gov Identfier)NCT02335424
2015-04-15 - 2019-12-31
Phase II
Terminated2
ICD-10C66
Malignant neoplasm of ureter
A Phase II Trial of Pembrolizumab (MK-3475) in Subjects with Advanced/Unresectable or Metastatic Urothelial Cancer
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Trial Applicant
Merck Sharp & Dohme (I.A.) LLC
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Sponsor
Merck Sharp & Dohme Corp.
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chin-Chung Yeh Division of Urology
- 何子龍 Division of Radiology
- Chao-Hsiang Chang Division of Urology
- Su-Peng Yeh Division of Hematology & Oncology
- Chi-Rei Yang Division of Urology
- Chi-Ping Huang Division of Urology
- Ching-Chan Lin Division of Hematology & Oncology
- Wen-Chi Chen Division of Urology
- Che-Hung Lin Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
Audit
None
Co-Principal Investigator
- Yeong-Shiau Pu Division of Urology
- Yu-Chieh Tsai Division of Hematology & Oncology
- - - Division of Urology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Advanced/Unresectable or Metastatic Urothelial Cancer
Objectives
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.
Test Drug
Pembrolizumab (MK-3475)
Active Ingredient
Pembrolizumab
Dosage Form
Injection
Dosage
100 mg/ 4 mL
Endpoints
Primary Outcome Measures :
1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 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. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented.
2. 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% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 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. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per RECIST 1.1 is presented.
3. 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% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 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. The percentage of participants who had a PD-L1 strong positive expression of ≥10% CPS and experienced a CR or PR per RECIST 1.1 is presented.
1. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 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. The percentage of participants who experienced a CR or PR per RECIST 1.1 is presented.
2. 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% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 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. The percentage of participants who had a PD-L1 positive expression of ≥1% CPS and experienced a CR or PR per RECIST 1.1 is presented.
3. 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% [ Time Frame: Through Database Cutoff Date of 26-Sep-2018 (up to approximately 41 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. The percentage of participants who had a PD-L1 strong positive expression of ≥10% CPS and experienced a CR or PR per RECIST 1.1 is presented.
Inclution Criteria
Inclusion Criteria:
• 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
• Measureable 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
• 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
• Measureable 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
Exclusion Criteria
Exclusion Criteria:
• 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
• 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
The Estimated Number of Participants
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Taiwan
6 participants
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Global
350 participants
