Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001)

Neoplasms Clinical Trial

Official title:

A Phase 1, Open-label, Multicenter Study of the Safety, Pharmacokinetics, and Pharmacodynamics of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05514444
• Other study ID #: 4464-001
• Secondary ID: MK-4464-0012021-
• Status: Recruiting
• Phase: Phase 1
• Start date: September 25, 2022
• Est. completion date: October 26, 2027

Study information

• Verified date: April 2024
• Source: Merck Sharp & Dohme LLC
• Contact: Toll Free Number
• Phone: 1-888-577-8839
• Email: Trialsites[@]merck.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: October 26, 2027
• Est. primary completion date: October 26, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 Exclusion Criteria include but are not limited to the following:

• Has had chemotherapy, definitive radiation, or biological cancer therapy within 4 weeks (2 weeks for palliative radiation) before the first dose of study intervention or has not recovered to CTCAE Grade 1 or better from any AEs that were due to cancer therapeutics administered more than 4 weeks earlier
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• Has clinically active central nervous system (CNS) metastases and/or carcinomatous meningitis
• Has an active infection requiring therapy
• History of an allogenic stem cell transplant or a solid organ transplant
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• Has an active autoimmune disease that has required systemic treatment in the past 2 years
• HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study
• Has not fully recovered from any effects of major surgery without significant detectable infection
• Has received radiation therapy to the lung that is >30 gray (Gy) within 6 months of the first dose of study treatment
• Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
• Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 28 days

Related Conditions & MeSH terms

• Advanced/Metastatic Solid Tumors
• Neoplasms

Intervention

Biological:
• MK-4464
MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation.
• Pembrolizumab
Pembrolizumab 200 mg administered as an IV infusion every three weeks.

Drug:
• 89Zr-MK-4464
89ZR-MK-4464 administered as an IV infusion on C1D1.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)	Toronto	Ontario
Israel	Rambam Health Care Campus-Oncology Division ( Site 0300)	Haifa
Israel	Hadassah Medical Center-Oncology ( Site 0302)	Jerusalem
Netherlands	Amsterdam UMC, locatie VUmc ( Site 0400)	Amsterdam	Noord-Holland
Netherlands	Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 0401)	Amsterdam	Noord-Holland
United States	The University of Louisville, James Graham Brown Cancer Center ( Site 0100)	Louisville	Kentucky

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)	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).	Up to approximately 21 days
Primary	Number of Participants Who Experience At Least One adverse event (AE)	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.	Up to approximately 27 months
Primary	Number of Participants Who Discontinue Study Treatment Due to an AE	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.	Up to approximately 24 months
Secondary	Minimum Plasma Concentration (Cmin) of MK-4464	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.	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
Secondary	Maximum Plasma Concentration (Cmax) of MK-4464	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.	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
Secondary	Area Under the Plasma Concentration-Time Curve (AUC) of MK-4464	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.	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
Secondary	Objective Response Rate (ORR)	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.	Up to 24 months

External Links

•   Merck Clinical Trials Information
•   Plain Language Summary