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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Neoplasms; Advanced/Metastatic Solid Tumors
• Intervention / Treatment: Biological: MK-4464; Biological: Pembrolizumab; Drug: 89Zr-MK-4464

• Study Type: Interventional
• Enrollment (Estimated): 260
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@merck.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)
      • Contact: Study Coordinator; Phone Number: 4169022235
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Health Care Campus-Oncology Division ( Site 0300)
    • Contact: Study Coordinator; Phone Number: 972535316961
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Medical Center-Oncology ( Site 0302)
    • Contact: Study Coordinator; Phone Number: 97226777957
• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1066CX
      • Recruiting
      • Nederlands Kanker Instituut - Antoni van Leeuwenhoek (NKI-AVL) ( Site 0401)
      • Contact: Study Coordinator; Phone Number: 31205129111
    • Amsterdam, Noord-Holland, Netherlands, 1081HV
      • Recruiting
      • Amsterdam UMC, locatie VUmc ( Site 0400)
      • Contact: Study Coordinator; Phone Number: 0031 6 2571678
• United States
  • Kentucky
    • Louisville, Kentucky, United States, 40245
      • Recruiting
      • The University of Louisville, James Graham Brown Cancer Center ( Site 0100)
      • Contact: Study Coordinator; Phone Number: 502-562-3429

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-4464; Participants will receive an intravenous (IV) infusion of MK-4464 administered in escalating doses every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of previous dose.	Biological: MK-4464; MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation.
Experimental: MK-4464 + Pembrolizumab; Participants will receive an IV infusion of MK-4464 administered in escalating doses and a 200 mg IV infusion of Pembrolizumab every 3 weeks for up to 35 cycles. Escalation to subsequent MK-4464 doses will be based on safety of MK-4464 monotherapy arm.	Biological: MK-4464; MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation.; Biological: Pembrolizumab; Pembrolizumab 200 mg administered as an IV infusion every three weeks.
Experimental: MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464; Participants will receive an IV infusion of 89Zr-MK-4464 + IV infusion of MK-4464 on Cycle 1 Day 1, followed by an IV infusion of MK-4464 + a 200 mg IV infusion of pembrolizumab starting on Cycle 2 Day 1 and every 3 weeks for up to 35 cycles. Each cycle=3 weeks. MK-4464 doses will be based on safety of MK-4464 monotherapy arm. Participants may receive a 200 mg IV infusion of pembrolizumab on cycle 36.	Biological: MK-4464; MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation.; Biological: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2022
• Primary Completion (Estimated): October 26, 2027
• Study Completion (Estimated): October 26, 2027

Study Registration Dates

• First Submitted: August 22, 2022
• First Submitted That Met QC Criteria: August 22, 2022
• First Posted (Actual): August 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 4464-001; MK-4464-001 (Other Identifier: Merck); 2021-005882-42 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No