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

NCT05514444 | Completed Phase 1 FDA Drug

• 5 other identifiers: 4464-001MK-4464-0012023-504855-28-00U1111-1290-26972021-005882-42
• Study Type: interventional
• Target: 64
• Locations: 4 countries
• Sites: 6

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.

Conditions

Advanced/Metastatic Solid Tumors; Neoplasms

Outcome Measures

Primary Outcomes (3)

• 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

• 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 Outcomes (4)

• 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

• 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

• 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

• Objective Response Rate (ORR)

  Up to 24 months

Study Arms (3)

MK-4464

EXPERIMENTAL

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 + Pembrolizumab

EXPERIMENTAL

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; Biological: Pembrolizumab

MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464

EXPERIMENTAL

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; Biological: Pembrolizumab; Drug: 89Zr-MK-4464

Interventions

MK-4464 BIOLOGICAL

MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation.

MK-4464; MK-4464 + Pembrolizumab; MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464

Pembrolizumab BIOLOGICAL

Pembrolizumab 200 mg administered as an IV infusion every three weeks.

MK-4464 + Pembrolizumab; MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464

89Zr-MK-4464 DRUG

89ZR-MK-4464 administered as an IV infusion on C1D1.

MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (6)

The University of Louisville, James Graham Brown Cancer Center ( Site 0100)

Louisville, Kentucky, 40245, United States

Location

Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)

Toronto, Ontario, M5G 2M9, Canada

Location

Rambam Health Care Campus-Oncology Division ( Site 0300)

Haifa, 3109601, Israel

Location

Hadassah Medical Center-Oncology ( Site 0302)

Jerusalem, 9112001, Israel

Location

Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 0401)

Amsterdam, North Holland, 1066CX, Netherlands

Location

Amsterdam UMC, locatie VUmc ( Site 0400)

Amsterdam, North Holland, 1081HV, Netherlands

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 24, 2022
• Study Start: September 25, 2022
• Primary Completion: September 18, 2025
• Study Completion: September 18, 2025
• Last Updated: October 9, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share

Locations

CA (1); US (1); NL (2); IL (2)