Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| MK-3475-04B | Other Identifier | MSD | |
| 2023-506385-30-00 | Registry Identifier | EU CT | |
| U1111-1293-7564 | Registry Identifier | UTN | |
| 2022-001371-14 | EudraCT Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
The master study for this substudy is MK-3475-U04/KEYMAKER-U04. The master study will not be screening any participants and will not be registered.
With Amendment 2, participants will discontinue treatment with coformulated vibostolimab/pembrolizumab (Arm B) and be transitioned to pembrolizumab only. Per protocol, no analysis of Part 2 primary or secondary outcome measures (including efficacy or safety) will occur since Part 2 of the study will no longer take place.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Coformulated favezelimab/pembrolizumab plus EV | Experimental | Participants will receive coformulated favezelimab/pembrolizumab (800 mg/200 mg) as an intravenous (IV) infusion on Day 1 of every 3-week cycle for up to ~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision. |
|
| Arm B: Coformulated vibostolimab/pembrolizumab plus EV | Experimental | Participants will receive coformulated vibostolimab/pembrolizumab (200 mg/200 mg) as an IV infusion on Day 1 of every 3-week cycle, for up to ~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision. |
|
| Arm C: Pembrolizumab plus EV | Active Comparator | Participants will receive 200 mg pembrolizumab as an IV infusion on Day 1 of every 3-week cycle for up to ~2 years (35 cycles) and EV at 1.25 mg/kg, administered as an IV infusion on Days 1 and 8 of every 3-week cycle, until disease progression, intolerable toxicity, or investigator decision. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Coformulated favezelimab/pembrolizumab | Biological | Coformulated favezelimab/pembrolizumab (800 mg/200 mg) IV infusion |
|
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: Objective Response Rate (ORR) | 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. | Up to ~4 years |
| Part 1: Percentage of Participants experiencing an Adverse Event (AE) | 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. | Up to ~4 years |
| Part 1: Percentage of Participants who Discontinue study interventions due to an AE | 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. | Up to ~4 years |
| Part 1: Percentage of Participants with Dose-limiting toxicities (DLT) | 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. | Up to 21 days |
| Part 2: Progression Free Survival (PFS) | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: PFS | 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. | Up to ~4 years |
| Part 1: Duration of Response (DOR) |
Not provided
Inclusion Criteria:
Must have histologically documented, locally advanced/metastatic urothelial carcinoma (la/mUC).
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:
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 \
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Moores Cancer Center ( Site 3028) | La Jolla | California | 92093-0698 | United States | ||
| University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 3045) |
Not provided
| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
| Plain Language Summary | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
In Part 1, participants will be randomized in a 1:1:1 ratio to receive either Arm A (coformulated favezelimab/pembrolizumab plus EV), Arm B (coformulated vibostolimab/pembrolizumab plus EV), or Arm C (pembrolizumab plus EV). If Part 2 is conducted, participants will be randomized in a 1:1:1 ratio to Arms A, B, and C or in a 1:1 ratio to Arms A and C or B and C, depending on the treatment arm(s) that are expanded in Part 2.
Not provided
Not provided
Not provided
Not provided
|
| Coformulated vibostolimab/pembrolizumab | Biological | Coformulated vibostolimab/pembrolizumab (200 mg/200 mg) IV infusion |
|
|
| EV | Combination Product | 1.25 mg/kg IV infusion |
|
|
| Pembrolizumab | Biological | 200 mg IV infusion |
|
|
| 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. |
| Up to ~4 years |
| Part 2: Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. OS will be reported for participants in Part 2. | Up to ~4 years |
| Part 2: ORR | 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. | Up to ~4 years |
| Part 2: DOR | 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. | Up to ~4 years |
| Part 2: Percentage of Participants experiencing an Adverse Event (AE) | 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. | Up to ~4 years |
| Part 2: Percentage of Participants who Discontinue study interventions due to an AE | 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. | Up to ~4 years |
| Part 2: Percentage of Participants with Dose-limiting toxicities (DLT) | 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. | Up to 21 days |
| 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) | 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. | Baseline and up to ~4 years |
| Part 1: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30 | 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. | Baseline and up to ~4 years |
| Part 1: Mean Change from Baseline in the European Quality of Life 5 Dimensions, 5-level Questionnaire (EQ-5D-5L) visual analog score (VAS) | 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. | Baseline and up to ~4 years |
| Part 2: Mean Change from baseline in the global health status/quality of life of the EORTC QLC-C30 (Items 29 and 30) | 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. | Baseline and up to ~4 years |
| Part 2: Mean Change from baseline in the physical functioning scale of the EORTC QLQ-C30 | 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. | Baseline and up to ~4 years |
| Part 2: Mean Change from Baseline in the EQ-5D-5L visual analog score (VAS) | 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. | Baseline and up to ~4 years |
| Part 1: Time-to-Deterioration (TTD) for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30) | 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. | Up to ~4 years |
| Part 1: TTD for the physical functioning scale of the EORTC QLQ-C30 | 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. | Up to ~4 years |
| Part 1: TTD for the EQ-5D-5L VAS | 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. | Up to ~4 years |
| Part 2: TTD for the global health status/quality of life of the EORTC QLQ-C30 (Items 29 and 30) | 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. | Up to ~4 years |
| Part 2: TTD for the physical functioning scale of the EORTC QLQ-C30 | 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. | Up to ~4 years |
| Part 2: TTD for the EQ-5D-5L VAS | 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. | Up to ~4 years |
| Orange |
| California |
| 92868 |
| United States |
| UCSF Medical Center at Mission Bay ( Site 3044) | San Francisco | California | 94158 | United States |
| Anschutz Cancer Pavilion ( Site 3017) | Aurora | Colorado | 80045 | United States |
| Emory University School of Medicine ( Site 3043) | Atlanta | Georgia | 30322 | United States |
| Indiana University Melvin and Bren Simon Cancer Center ( Site 3011) | Indianapolis | Indiana | 46202 | United States |
| Dana-Farber Cancer Institute ( Site 3047) | Boston | Massachusetts | 02115 | United States |
| Siteman Cancer Center ( Site 3038) | St Louis | Missouri | 63108 | United States |
| Icahn School of Medicine at Mount Sinai ( Site 3018) | New York | New York | 10029 | United States |
| Memorial Sloan Kettering Cancer Center ( Site 3031) | New York | New York | 10065 | United States |
| Duke Cancer Institute ( Site 3027) | Durham | North Carolina | 27710 | United States |
| Cleveland Clinic-Taussig Cancer Center ( Site 3036) | Cleveland | Ohio | 44195 | United States |
| UPMC Hillman Cancer Center ( Site 3014) | Pittsburgh | Pennsylvania | 15232 | United States |
| Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 3041) | Salt Lake City | Utah | 84112 | United States |
| Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Site 3951) | Brisbane | Queensland | 4029 | Australia |
| Austin Health-Cancer Clinical Trials Centre ( Site 3950) | Heidelberg | Victoria | 3084 | Australia |
| The Ottawa Hospital - General Campus-The Ottawa Hospital Cancer Centre ( Site 3105) | Ottawa | Ontario | K1H 8L6 | Canada |
| Sunnybrook Research Institute - Odette Cancer Centre ( Site 3108) | Toronto | Ontario | M4N 3M5 | Canada |
| Princess Margaret Cancer Centre ( Site 3106) | Toronto | Ontario | M5G 2M9 | Canada |
| FALP-UIDO ( Site 3151) | Santiago | Region M. de Santiago | 7500921 | Chile |
| Bradfordhill-Clinical Area ( Site 3155) | Santiago | Region M. de Santiago | 8420383 | Chile |
| ONCOCENTRO APYS-ACEREY ( Site 3158) | Viña del Mar | Valparaiso | 2520598 | Chile |
| Bradford Hill Norte ( Site 3152) | Antofagasta | 1240000 | Chile |
| CHU de Bordeaux Hop St ANDRE ( Site 3607) | Bordeaux | Aquitaine | 33075 | France |
| Centre Georges François Leclerc-Centre de recherche clinique ( Site 3608) | Dijon | Cote-d Or | 21079 | France |
| Oncopole Claudius Regaud ( Site 3610) | Toulouse | Haute-Garonne | 31059 | France |
| centre hospitalier lyon sud ( Site 3606) | Pierre-Bénite | Rhone | 69310 | France |
| Hôpital Européen Georges Pompidou ( Site 3605) | Paris | 75015 | France |
| Rambam Health Care Campus-Oncology Division ( Site 3501) | Haifa | 3109601 | Israel |
| Rabin Medical Center-Oncology ( Site 3504) | Petah Tikva | 4941492 | Israel |
| Sheba Medical Center-ONCOLOGY ( Site 3503) | Ramat Gan | 5265601 | Israel |
| Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 3406) | Naples | Campania | 80131 | Italy |
| Fondazione IRCCS Istituto Nazionale dei Tumori-Struttura Complessa Oncologia Medica 1 ( Site 3405) | Milan | Lombardy | 20133 | Italy |
| Ospedale San Raffaele-Oncologia Medica ( Site 3403) | Milan | 20132 | Italy |
| Maastricht UMC+ ( Site 3304) | Maastricht | Limburg | 6229 HX | Netherlands |
| Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL)-medical oncology ( Site 3302) | Amsterdam | North Holland | 1066 CX | Netherlands |
| Erasmus Medisch Centrum-Medical Oncology ( Site 3303) | Rotterdam | South Holland | 3015 GD | Netherlands |
| Severance Hospital, Yonsei University Health System-Medical oncology ( Site 3903) | Seoul | 03722 | South Korea |
| Asan Medical Center-Department of Oncology ( Site 3901) | Seoul | 05505 | South Korea |
| Samsung Medical Center ( Site 3902) | Seoul | 06351 | South Korea |
| Hospital Universitari Vall d'Hebron ( Site 3767) | Barcelona | Catalonia | 08035 | Spain |
| Hospital Clinico San Carlos ( Site 3765) | Madrid | 28040 | Spain |
| Chang Gung Memorial Hospital at Kaohsiung-Oncology and Hematology ( Site 3802) | Kaohsiung City | 83301 | Taiwan |
| National Cheng Kung University Hospital-Clinical Trial Center ( Site 3803) | Tainan | 704 | Taiwan |
| National Taiwan University Hospital-Oncology ( Site 3801) | Taipei | 10002 | Taiwan |
| St Bartholomew's Hospital-Centre for Experimental Cancer Medicine ( Site 3206) | London | London, City of | EC1A 7BE | United Kingdom |
| ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 3201) | London | London, City of | SW3 6JJ | United Kingdom |
| ID | Term |
|---|---|
| D002295 | Carcinoma, Transitional Cell |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided