Advanced/Metastatic Solid Tumors, Neoplasms
Conditions
Brief summary
The purpose of this study is to assess the safety, pharmacokinetics, and preliminary efficacy of MK-4464 as monotherapy and in combination with pembrolizumab in participants with advanced/metastatic solid tumors.
Interventions
BIOLOGICALMK-4464
MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation.
BIOLOGICALPembrolizumab
Pembrolizumab 200 mg administered as an IV infusion every three weeks.
DRUG89Zr-MK-4464
89ZR-MK-4464 administered as an IV infusion on C1D1.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The key Inclusion Criteria include but are not limited to the following: * Have a histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, been intolerant to, been ineligible for, or refused all treatment known to confer clinical benefit * Must submit a baseline tumor sample for analysis * Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale * Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART) * Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before randomization.
Exclusion criteria
The key
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) | Up to approximately 21 days | A DLT is any toxicity assessed by the investigator to be possibly, probably, or definitely related to study intervention administration that results in a change to a given dose or a delay in initiating the next cycle. All toxicities will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). |
| Number of Participants Who Experience At Least One adverse event (AE) | Up to approximately 27 months | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 24 months | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minimum Plasma Concentration (Cmin) of MK-4464 | Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days | Cmin is the minimum concentration of the drug observed in plasma. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Cmin of MK-4464. |
| Objective Response Rate (ORR) | Up to 24 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 assessment will be presented. |
| Maximum Plasma Concentration (Cmax) of MK-4464 | Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days | Cmax is the maximum concentration of the drug observed in plasma. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Cmax of MK-4464. |
| Area Under the Plasma Concentration-Time Curve (AUC) of MK-4464 | Once daily on Day 2, 3, 5, 8, 15 of Cycle 1 and 4, Pre-dose and immediately Post-dose Day 1 Cycle 1, 2, 3, 4, Pre-dose Day 1 Cycles 5, 6, 7, 8, and every 4 cycles thereafter through Cycle 35, 30 days post last dose (up to ~25 months); Cycle = 21 days | AUC is a measure of the extrapolated mean concentration in serum. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine AUC of MK-4464. |
Countries
Canada, Israel, Netherlands, United States
Outcome results
None listed