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| ID | Type | Description | Link |
|---|---|---|---|
| MK-3475-04C | Other Identifier | MSD | |
| 2023-506387-14-00 | Registry Identifier | EU CT | |
| U1111-1293-7631 | Registry Identifier | UTN |
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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 safety and preliminary efficacy of sacituzumab tirumotecan plus enfortumab vedotin (EV). Part 2 will be based on Part 1 results and will evaluate the efficacy, pharmacokinetics, and safety of sacituzumab tirumotecan plus EV in combination with pembrolizumab in participants with advanced urothelial carcinoma.
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.
As of Amendment 5, Part 2 will not be conducted. No participants will be enrolled in Part 2, and no data for Part 2 will be collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sacituzumab tirumotecan plus EV | Experimental | Participants will receive sacituzumab tirumotecan as an intravenous (IV) infusion and EV as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision. |
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| Sacituzumab tirumotecan plus EV and pembrolizumab | Experimental | Participants will receive sacituzumab tirumotecan as an IV infusion and EV as an IV infusion on Days 1 and 8 of every 3-week cycle until disease progression, intolerable toxicity, or investigator decision. Participants will also receive pembrolizumab 200 mg as an IV infusion on Day 1 of every 3-week cycle for up to ~2 years (35 cycles). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sacituzumab tirumotecan | Biological | IV infusion at different dose levels |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 1: Percentage of Participants Who Experienced At Least One 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 ~3 years |
| Part 1: Percentage of Participants Who Discontinued Study Treatment 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 treatment due to an AE in Part 1 will be reported. | Up to ~2 years |
| Part 2: Percentage of Participants with 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 NCI CTCAE 5.0. The number of participants who experience a DLT in Part 2 will be reported. | Up to 21 days |
| Part 2: Percentage of Participants Who Experienced At Least One 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Part 1: ORR | ORR is defined as the percentage of participants who achieve a confirmed CR or PR per RECIST 1.1 as assessed by investigator. ORR will be reported for participants in Part 1. | Up to ~3 years |
| Part 2: Duration of Response (DOR) |
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Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco HDFCCC ( Site 4044) | San Francisco | California | 94158 | United States | ||
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| Label | URL |
|---|---|
| Merck Clinical Trials Information | View source |
| Plain Language Summary | View source |
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Part 1 is non-randomized open-label. Part 2 is randomized open-label (as of Amendment 5, Part 2 will not be conducted).
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| Enfortumab Vedotin | Biological | IV infusion at different dose levels |
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| Pembrolizumab | Biological | 200 mg IV infusion |
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| Supportive care measures | Drug | Participants are allowed to take supportive care measures at the discretion of the investigator. Prophylactic supportive care measures may include but are not limited to antiemetic agents, antidiarrheal agents, granulocyte and erythroid growth factors, and blood transfusions. |
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| Up to ~3 years |
| Part 2: Percentage of Participants Who Discontinued Study Treatment 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 treatment due to an AE in Part 2 will be reported. | Up to ~2 years |
| Part 2: Objective Response Rate (ORR) | ORR is defined as the percentage of participants who achieve a confirmed complete response (CR) (disappearance of all target lesions) or partial response (PR) (at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by investigator. ORR will be reported for participants in Part 2. | Up to ~3 years |
For participants who demonstrate confirmed CR or PR per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by investigator will be presented.
| Up to ~3 years |
| Part 1: Maximum Serum Concentration (Cmax) of Sacituzumab Tirumotecan-Antibody-Drug Conjugate (ADC) | Blood samples collected at designated time points will be used to determine the Cmax of sacituzumab tirumotecan-ADC in Part 1. | Days 1, 8, 15 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, Day 1 of Cycles 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 1: Serum Trough Concentration (Ctrough) of Sacituzumab Tirumotecan-ADC | Blood samples collected at designated time points will be used to determine the Ctrough of sacituzumab tirumotecan-ADC in Part 1. | Days 1, 8, 15 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, Day 1 of Cycles 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 1: Cmax of Free Payload for Sacituzumab Tirumotecan | Blood samples collected at designated time points will be used to determine the Cmax of free payload for sacituzumab tirumotecan in Part 1. | Days 1, 8, 15 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, Day 1 of Cycles 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 1: Ctrough of Free Payload for Sacituzumab Tirumotecan | Blood samples collected at designated time points will be used to determine the Ctrough of free payload for sacituzumab tirumotecan in Part 1. | Days 1, 8, 15 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, Day 1 of Cycles 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 1: Cmax of Enfortumab Vedotin-ADC | Blood samples collected at designated time points will be used to determine the Cmax of enfortumab vedotin-ADC in Part 1. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, and Day 1 of Cycles 4 and 8 |
| Part 1: Ctrough of Enfortumab Vedotin-ADC | Blood samples collected at designated time points will be used to determine the Ctrough of enfortumab vedotin-ADC in Part 1. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, and Day 1 of Cycles 4 and 8 |
| Part 1: Cmax of Free Payload for Enfortumab Vedotin | Blood samples collected at designated time points will be used to determine the Cmax of free payload for EV in Part 1. | Days 1, 8, 15 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, and Day 1 of Cycles 4 and 8 |
| Part 1: Ctrough of Free Payload for Enfortumab Vedotin | Blood samples collected at designated time points will be used to determine the Ctrough of free payload for EV in Part 1. | Days 1, 8, 15 of Cycle 1 (each cycle is 21 days), Day 1 of Cycle 2, Days 1 and 8 of Cycle 3, and Day 1 of Cycles 4 and 8 |
| Part 1: Incidence of Antidrug Antibodies (ADA) to Sacituzumab Tirumotecan | Blood samples collected at designated timepoints will be used to determine the ADA response to sacituzumab tirumotecan. The incidence of ADAs over time in Part 1 will be presented. | Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 1: Incidence of ADA to Enfortumab Vedotin | Blood samples collected at designated timepoints will be used to determine the ADA response to sacituzumab tirumotecan. The incidence of ADAs over time in Part 1 will be presented. | Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4 and 8 |
| Part 2: Cmax of Sacituzumab Tirumotecan-ADC | Blood samples collected at designated time points will be used to determine the Cmax of sacituzumab tirumotecan-ADC in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Ctrough of Sacituzumab Tirumotecan-ADC | Blood samples collected at designated time points will be used to determine the Ctrough of sacituzumab tirumotecan-ADC in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Cmax of Free Payload for Sacituzumab Tirumotecan | Blood samples collected at designated time points will be used to determine the Cmax of free payload for sacituzumab tirumotecan in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Ctrough of Free Payload for Sacituzumab Tirumotecan | Blood samples collected at designated time points will be used to determine the Ctrough of free payload for sacituzumab tirumotecan in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Cmax of Enfortumab Vedotin-ADC | Blood samples collected at designated time points will be used to determine the Cmax of enfortumab vedotin-ADC in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 |
| Part 2: Ctrough of Enfortumab Vedotin-ADC | Blood samples collected at designated time points will be used to determine the Ctrough of enfortumab vedotin-ADC in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 |
| Part 2: Cmax of Free Payload for Enfortumab Vedotin | Blood samples collected at designated time points will be used to determine the Cmax of free payload for EV in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 |
| Part 2: Ctrough of Free Payload for Enfortumab Vedotin | Blood samples collected at designated time points will be used to determine the Ctrough of free payload for EV in Part 2. | Days 1 and 8 of Cycle 1 (each cycle is 21 days), Day 1 of Cycles 2, 4 and 8 |
| Part 2: Cmax of Pembrolizumab-ADC | Blood samples collected at designated time points will be used to determine the Cmax of pembrolizumab-ADC. | Days 1 of Cycles 1 (each cycle is 21 days), 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Ctrough of Pembrolizumab-ADC | Blood samples collected at designated time points will be used to determine the Ctrough of pembrolizumab-ADC. | Days 1 of Cycles 1 (each cycle is 21 days), 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Cmax of Free Payload for Pembrolizumab | Blood samples collected at designated time points will be used to determine the Cmax of free payload for pembrolizumab. | Days 1 of Cycles 1 (each cycle is 21 days), 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Ctrough of Free Payload for Pembrolizumab | Blood samples collected at designated time points will be used to determine the Ctrough of free payload for pembrolizumab. | Days 1 of Cycles 1 (each cycle is 21 days), 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Incidence of ADA to Sacituzumab Tirumotecan | Blood samples collected at designated timepoints will be used to determine the ADA response to sacituzumab tirumotecan. The incidence of ADAs over time in Part 2 will be presented. | Day 1 of Cycles 1 (each cycle is 21 days), 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| Part 2: Incidence of ADA to Enfortumab Vedotin | Blood samples collected at designated timepoints will be used to determine the ADA response to EV. The incidence of ADAs over time in Part 2 will be presented. | Day 1 of Cycles 1 (each cycle is 21 days), 2, 4 and 8 |
| Part 2: Incidence of ADA to Pembrolizumab | Blood samples collected at designated timepoints will be used to determine the ADA response to pembrolizumab. The incidence of ADAs over time be presented. | Day 1 of Cycles 1 (each cycle is 21 days), 2, 4 and 8 and every 4 cycles thereafter up to Cycle 35, at end of treatment, and at 30 days post last dose |
| University of Chicago Medical Center ( Site 4037) |
| Chicago |
| Illinois |
| 60637 |
| United States |
| Indiana University Melvin and Bren Simon Cancer Center ( Site 4011) | Indianapolis | Indiana | 46202 | United States |
| Dana-Farber Cancer Institute ( Site 4047) | Boston | Massachusetts | 02115 | United States |
| Siteman Cancer Center ( Site 4038) | St Louis | Missouri | 63108 | United States |
| Icahn School of Medicine at Mount Sinai ( Site 4018) | New York | New York | 10029 | United States |
| Cleveland Clinic-Taussig Cancer Center ( Site 4036) | Cleveland | Ohio | 44195 | United States |
| Huntsman Cancer Institute-HCI Clinical Trials Office ( Site 4041) | Salt Lake City | Utah | 84112 | United States |
| The Ottawa Hospital - General Campus ( Site 4105) | Ottawa | Ontario | K1H 8L6 | Canada |
| Princess Margaret Cancer Centre ( Site 4106) | Toronto | Ontario | M5G 2M9 | Canada |
| Centre Hospitalier Lyon Sud ( Site 4606) | Pierre-Bénite | Auvergne-Rhône-Alpes | 69310 | France |
| Rambam Health Care Campus ( Site 4501) | Haifa | 3109601 | Israel |
| Rabin Medical Center-Oncology ( Site 4504) | Petah Tikva | 4941492 | Israel |
| Sheba Medical Center-ONCOLOGY ( Site 4503) | Ramat Gan | 5265601 | Israel |
| Ospedale San Raffaele-Oncologia Medica ( Site 4403) | Milan | Lombardy | 20132 | Italy |
| Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 4405) | Milan | 20133 | Italy |
| Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 4406) | Naples | 80131 | Italy |
| Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 4302) | Amsterdam | North Holland | 1066 CX | Netherlands |
| Severance Hospital, Yonsei University Health System-Medical oncology ( Site 4903) | Seoul | 03722 | South Korea |
| Asan Medical Center-Department of Oncology ( Site 4901) | Seoul | 05505 | South Korea |
| Samsung Medical Center ( Site 4902) | Seoul | 06351 | South Korea |
| Hospital Universitari Vall d'Hebron-Oncology ( Site 4767) | Barcelona | 08035 | Spain |
| Hospital Clinico San Carlos ( Site 4765) | Madrid | 28040 | Spain |
| National Cheng Kung University Hospital-Clinical Trial Center ( Site 4803) | Tainan | 704 | Taiwan |
| St Bartholomew s Hospital ( Site 4206) | London | London, City of | EC1A 7BE | United Kingdom |
| ID | Term |
|---|---|
| D002295 | Carcinoma, Transitional Cell |
| C565324 | Parkinson Disease 4, Autosomal Dominant Lewy Body |
| ID | Term |
|---|---|
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000632577 | enfortumab vedotin |
| C582435 | pembrolizumab |
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