Advanced/Metastatic Solid TumorsPhase 1NCT05514444
Study of MK-4464 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors (MK-4464-001)
A Phase 1 study testing MK-4464, Pembrolizumab and 89Zr-MK-4464 in people with Advanced/Metastatic Solid Tumors and Neoplasms, run by Merck Sharp & Dohme LLC at 6 sites in 4 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced/Metastatic Solid Tumors, Neoplasms
- What is being tested?
- MK-4464, Pembrolizumab and 89Zr-MK-4464
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 6 sitesin 4 countries
- Study dates
- 25 Sep 2022to 18 Sep 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
6 sites in 4 countries.
6 sites in 4 countries
Israel2 sites
Rambam Health Care Campus-Oncology Division ( Site 0300)
Haifa, 3109601
Hadassah Medical Center-Oncology ( Site 0302)
Jerusalem, 9112001
Netherlands2 sites
Nederlands Kanker Instituut - Antoni van Leeuwenhoek - NKI-AVL ( Site 0401)
Amsterdam, North Holland, 1066CX
Amsterdam UMC, locatie VUmc ( Site 0400)
Amsterdam, North Holland, 1081HV
United States1 site
The University of Louisville, James Graham Brown Cancer Center ( Site 0100)
Louisville, Kentucky, 40245
Canada1 site
Princess Margaret Cancer Centre-Division of Medical Oncology and Hematology ( Site 0201)
Toronto, Ontario, M5G 2M9
About this study
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
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
- Being tested
- MK-4464, Pembrolizumab, 89Zr-MK-4464
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-4464Biological
MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation.
PembrolizumabBiological
Pembrolizumab 200 mg administered as an IV infusion every three weeks.
89Zr-MK-4464Drug
89ZR-MK-4464 administered as an IV infusion on C1D1.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Biological: MK-4464; Biological: Pembrolizumab; Drug: 89Zr-MK-4464 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: Up to approximately 24 months
Secondary outcomes (4)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2022
- Study start25 Sep 2022
- Primary completion18 Sep 2025
- Study completion18 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced/Metastatic Solid TumorsStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck Sharp & Dohme LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05514444
- Sponsor's protocol ID
- 4464-001
- Other IDs
- MK-4464-001, 2023-504855-28-00, U1111-1290-2697, 2021-005882-42, 2023
- Status last verified
- Oct 2025
- First submitted
- 22 Aug 2022
- Last updated
- 9 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05514444
- Acronym / sponsor ID
- 4464-001
- Conditions
- Advanced/Metastatic Solid Tumors, Neoplasms
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 25 Sep 2022 (actual)
- Primary completion
- 18 Sep 2025 (actual)
- Study completion
- 18 Sep 2025 (actual)
- First posted
- 24 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MK-4464 | Experimental | Biological: MK-4464Participants 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. |
| MK-4464 + Pembrolizumab | Experimental | Biological: MK-4464, Biological: PembrolizumabParticipants 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. |
| MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464 | Experimental | Biological: MK-4464, Biological: Pembrolizumab, Drug: 89Zr-MK-4464Participants 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MK-4464MK-4464 administered as an IV infusion every three weeks according to allocation and dose escalation. | Biological | MK-4464, MK-4464 + Pembrolizumab, MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464 |
| PembrolizumabPembrolizumab 200 mg administered as an IV infusion every three weeks. | Biological | MK-4464 + Pembrolizumab, MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464 |
| 89Zr-MK-446489ZR-MK-4464 administered as an IV infusion on C1D1. | Drug | MK-4464 + Pembrolizumab + Zirconium 89 (89Zr)-MK-4464 |
Primary outcome
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time frame: 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)
Time frame: 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
Time frame: 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.
4 secondary outcomes
Minimum Plasma Concentration (Cmin) of MK-4464
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: Up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2025.
- Merck Clinical Trials InformationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck Sharp & Dohme LLC
6 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MK-4464, Pembrolizumab and 89Zr-MK-4464 in people with Advanced/Metastatic Solid Tumors and Neoplasms, run by Merck Sharp & Dohme LLC at 6 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Israel, Netherlands, United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) (time frame: Up to approximately 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2025.