> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-study-of-efficacy-and-safety-of-pembrolizumab-plus-48b8dafa-2b39-4868-b35c-ff8a4b43b198 > Record changed: 2026-10-13 # A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04) NCT05845814 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) Phase Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) Recruitment status Active, not recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) Participants 390 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) Lead sponsor Merck Sharp & Dohme LLC Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) Start date 2023-06-23 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) Number of sites 47 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Title and summary **Summary** This study is a substudy being conducted under one pembrolizumab umbrella master study KEYMAKER-U04\. The substudy will consist of 2 parts. Part 1 will evaluate the efficacy and safety of coformulated favezelimab/pembrolizumab plus EV and coformulated vibostolimab/pembrolizumab plus EV relative to pembrolizumab plus EV. There will be no comparison of coformulated favezelimab/pembrolizumab plus EV versus coformulated vibostolimab/pembrolizumab plus EV. If ORR and/or DRR are substantially better on coformulated favezelimab/pembrolizumab plus EV and/or coformulated vibostolimab/pembrolizumab plus EV compared with pembrolizumab plus EV, after evaluation of the totality of data, the sponsor might consider Part 2 (expansion) to further characterize the efficacy and safety of the treatment arms under study. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Short title** A Study of Efficacy and Safety of Pembrolizumab Plus Enfortumab Vedotin (EV) +/- Investigational Agents in First-Line Metastatic Urothelial Carcinoma (mUC) (MK-3475-04B/KEYMAKER-U04) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Official title** A Phase 1/2 Randomized, Umbrella Study to Evaluate the Safety and Efficacy of Pembrolizumab Plus Enfortumab Vedotin (EV) in Combination With Investigational Agents Versus Pembrolizumab Plus EV, as First-Line Treatment for Participants With Advanced Urothelial Carcinoma (KEYMAKER-U04): Substudy 04B Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Status and phase **Control arm** Active comparator Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Recruitment status** Active, not recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Phase** Phase 1/Phase 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Dates **Completion date** 2027-05-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **First posted** 2023-05-06 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Registry last updated** 2025-09-10 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Primary completion date** 2027-05-31 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Start date** 2023-06-23 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Size and sites **Participants** 390 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Planned participants** 390 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Protocol amendments** 2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Number of sites** 47 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Sponsor and oversight **Data monitoring committee** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Lead sponsor** Merck Sharp & Dohme LLC Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Identifiers **Registry ID** NCT05845814 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **ClinicalTrials.gov ID** NCT05845814 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** No masking Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Outcomes ### Primary outcomes 1. Part 1: Objective Response Rate (ORR) Timeframe: Up to \~4 years ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by blinded independent central review (BICR). ORR will be reported for participants in Part 1. 2. Part 1: Percentage of Participants experiencing an Adverse Event (AE) Timeframe: Up to \~4 years An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants experiencing an AE in Part 1 will be reported. 3. Part 1: Percentage of Participants who Discontinue study interventions due to an AE Timeframe: Up to \~4 years An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinue study interventions due to an AE in Part 1 will be reported. 4. Part 1: Percentage of Participants with Dose-limiting toxicities (DLT) Timeframe: Up to 21 days A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0). The number of participants who experience a DLT in Part 1 will be reported. 5. Part 2: Progression Free Survival (PFS) Timeframe: Up to \~4 years PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PFS will be reported for participants in Part 2. ### Secondary outcomes 1. Part 1: PFS Timeframe: Up to \~4 years PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PFS will be reported for participants in Part 1. 2. Part 1: Duration of Response (DOR) Timeframe: Up to \~4 years For participants who demonstrate confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR will be reported for participants in Part 1. 3. Part 2: Overall Survival (OS) Timeframe: Up to \~4 years OS is defined as the time from randomization to death due to any cause. OS will be reported for participants in Part 2. 4. Part 2: ORR Timeframe: Up to \~4 years ORR is defined as the percentage of participants who achieve a confirmed CR or PR per RECIST 1.1 as assessed by BICR. ORR will be reported for participants in Part 2. 5. Part 2: DOR Timeframe: Up to \~4 years For participants who demonstrate confirmed CR or PR, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR will be reported for participants in Part 2. 6. Part 2: Percentage of Participants experiencing an Adverse Event (AE) Timeframe: Up to \~4 years An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants experiencing an AE in Part 2 will be reported. 7. Part 2: Percentage of Participants who Discontinue study interventions due to an AE Timeframe: Up to \~4 years An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinue study interventions due to an AE in Part 2 will be reported. 8. Part 2: Percentage of Participants with Dose-limiting toxicities (DLT) Timeframe: Up to 21 days A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE 5.0). The number of participants who experience a DLT in Part 2 will be reported. 9. Part 1: Mean Change from baseline in the global health status/quality of life of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLC-C30) (Items 29 and 30) Timeframe: Baseline and up to \~4 years Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30\. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 1. 10. Part 1: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30 Timeframe: Baseline and up to \~4 years Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30\. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 1. 11. Part 1: Mean Change from Baseline in the European Quality of Life 5 Dimensions, 5-level Questionnaire (EQ-5D-5L) visual analog score (VAS) Timeframe: Baseline and up to \~4 years The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 1. 12. Part 2: Mean Change from baseline in the global health status/quality of life of the EORTC QLC-C30 (Items 29 and 30) Timeframe: Baseline and up to \~4 years Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30\. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 2. 13. Part 2: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30 Timeframe: Baseline and up to \~4 years Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30\. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 2. 14. Part 2: Mean Change from Baseline in the EQ-5D-5L visual analog score (VAS) Timeframe: Baseline and up to \~4 years The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. The mean change from baseline will be reported for Part 2. 15. Part 1: Time-to-Deterioration (TTD) for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30) Timeframe: Up to \~4 years Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30\. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 1. 16. Part 1: TTD for the physical functioning scale of the EORTC QLQ-C30 Timeframe: Up to \~4 years Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30\. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 1. 17. Part 1: TTD for the EQ-5D-5L VAS Timeframe: Up to \~4 years The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first EQ-5D-5L VAS assessment to deterioration (defined as ≥7-point decrease in EQ-5D-5L VAS score more from baseline) or death, whichever occurs first. The TTD in EQ-5D-5L VAS score of participants will be reported for Part 1. 18. Part 2: TTD for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30) Timeframe: Up to \~4 years Participants are asked to answer questions 29 and 30 from the EORTC QLC-C30\. Questions 29 and 30 use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 2. 19. Part 2: TTD for the physical functioning scale of the EORTC QLQ-C30 Timeframe: Up to \~4 years Participants are asked to answer questions about their physical functioning from the EORTC QLC-C30\. These questions use a 4-point scale (1=not at all to 4=very much) to evaluate overall health and quality of life. Scores were transformed to a range of 0 to 100 using a standard EORTC algorithm. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first GHS/QoL assessment to deterioration (defined as ≥10-point decrease in GHS/QoL score from baseline) or death, whichever occurs first. The TTD in GHS/QoL score of participants will be reported for Part 2. 20. Part 2: TTD for the EQ-5D-5L VAS Timeframe: Up to \~4 years The EQ-5D-5L is a descriptive five-dimensional system of evaluation. The five dimensions are mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Participants rate each dimension on 5 levels ranging from 1 (no problems) to 5 (extreme problems). The EQ-5D-5L also includes a graded (0 to 100) vertical visual analog scale on which the participant rates their general state of health. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. TTD is defined as the time from the first EQ-5D-5L VAS assessment to deterioration (defined as ≥7-point decrease in EQ-5D-5L VAS score more from baseline) or death, whichever occurs first. The TTD in EQ-5D-5L VAS score of participants will be reported for Part 2. Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05845814) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Healthy volunteers** No ### Inclusion criteria - Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC). - Participants with mixed histology are eligible provided the urothelial component is ≥50% (and <10% plasmacytoid component) - Participants whose tumors contain any neuroendocrine component are not eligible (variant histology to be confirmed locally) - Must not have received prior systemic therapy for la/mUC. The following therapies in earlier disease setting (eg, muscle-invasive urothelial carcinoma (MIUC)) are permitted: - Participants that received neoadjuvant or adjuvant chemotherapy are permitted. - Participants who received anti- programmed cell death 1 protein (PD-1) or programmed cell death ligand 1 (PD-L1) therapy for an earlier disease stage (eg, NMIBC, MIUC) with progression/recurrence >12 months from completion of therapy are permitted. - Must provide an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion demonstrating UC, not previously irradiated, and adequate for biomarker evaluation. A newly obtained biopsy is strongly preferred, but not required if archival tissue is evaluable. - Any AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Endocrine-related AEs adequately treated with hormone replacement or with