Bladder Cancer
Conditions
Brief summary
Researchers are looking for new ways to treat people with urothelial cancer (UC) that is locally advanced or metastatic. The standard treatment for locally advanced or metastatic UC is enfortumab vedotin (EV) given with pembrolizumab. The goals of this study are to learn about: * The safety of the study treatment when given with standard treatment and if people tolerate it * The number of people who have the cancer respond (cancer gets smaller or goes away) with the new study treatment when given with standard treatment.
Detailed description
This is a substudy of the master protocol MK-3475-U04 (KEYMAKER-U04)
Interventions
DRUGMK-3120
Administered via intravenous (IV) infusion on day 1 and day 8 of each 3-week cycle
DRUGEV
Administered via IV infusion on day 1 and day 8 of each 3-week cycle
BIOLOGICALPembrolizumab
Administered via IV infusion on day 1 of each 3-week cycle
DRUGRescue Medication
Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medication is Granulocyte Colony-Stimulating Factor (G-CSF).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has histologically documented urothelial carcinoma (UC) that is locally advanced and unresectable or metastatic * Must provide a newly obtained or archival tumor tissue sample (core or excisional biopsy) * Must not have received prior systemic therapy for locally advanced or metastatic UC * If infected with Human Immunodeficiency Virus (HIV), has well controlled HIV on antiretroviral therapy * If positive for hepatitis B surface antigen, has received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and has undetectable HBV viral load before randomization * If participant has a history of hepatitis C virus (HCV), has undetectable HCV viral load before randomization
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 27 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported. |
| Number of Participants Who Experience a Dose Limiting Toxicity (DLT) | Up to approximately 21 days | DLT will be defined as any drug-related AE observed during the DLT evaluation period that results in a change to a given dose or a delay in initiating the next treatment. The number of participants who experience a DLT as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 will be presented. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 24 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that discontinue study intervention due to an AE will be reported. |
| Objective Response Rate (ORR) as Assessed by Investigator | Up to approximately 58 months | ORR is defined as the percentage of participants with 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 Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Investigator will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) as Assessed by Investigator | Up to approximately 58 months | For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. 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. |
| Serum Maximum Concentration (Cmax) of MK-3120 Antibody-Drug Conjugate (ADC) | Predose and at designated time points post-dose (up to approximately 24 months) | Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-3120 ADC. |
| Serum Trough Concentration (Ctrough) of MK-3120 ADC | Predose and at designated time points post-dose (up to approximately 24 months) | Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of MK-3120 ADC. |
| Serum Cmax of MK-3120 Total Antibodies (TAb) | Predose and at designated time points post-dose (up to approximately 24 months) | Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-3120 TAb. |
| Serum Ctrough of MK-3120 TAb | Predose and at designated time points post-dose (up to approximately 24 months) | Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of MK-3120 TAb. |
| Plasma Cmax of MK-3120 Free Payload | Predose and at designated time points post-dose (up to approximately 24 months) | Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of MK-3120 Free Payload. |
| Plasma Ctrough of MK-3120 Free Payload | Predose and at designated time points post-dose (up to approximately 24 months) | Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of MK-3120 Free Payload. |
| Serum Cmax of EV ADC | Predose and at designated time points post-dose (up to approximately 24 months) | Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of EV ADC. |
| Serum Ctrough of EV ADC | Predose and at designated time points post-dose (up to approximately 24 months) | Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of EV ADC. |
| Serum Cmax of EV TAb | Predose and at designated time points post-dose (up to approximately 24 months) | Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of Enfortumab Vedotin (EV) TAb. |
| Serum Ctrough of EV TAb | Predose and at designated time points post-dose (up to approximately 24 months) | Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of EV TAb. |
| Plasma Cmax of EV Free Payload | Predose and at designated time points post-dose (up to approximately 24 months) | Cmax is defined as the peak concentration over the dosing interval. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Cmax of Enfortumab Vedotin (EV) Free Payload. |
| Plasma Ctrough of EV Free Payload | Predose and at designated time points post-dose (up to approximately 24 months) | Ctrough is defined as the trough concentration. Blood samples collected pre-dose and at multiple timepoints post-dose will be used to determine Ctrough of EV Free Payload. |
Countries
France, Israel, Netherlands, South Korea, Spain, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed