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Multiple Myeloma in RelapsePhase 1NCT04184050

Study of HPN217 in Participants With Relapsed/Refractory Multiple Myeloma MK-4002 (MK-4002-001)

A Phase 1 study testing MK-4002 in people with Multiple Myeloma in Relapse and Multiple Myeloma, run by Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 12 sites in 3 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Researchers want to learn if MK-4002 (also known as HPN217) can treat relapsed or refractory multiple myeloma (RRMM). The goals of this study are to learn about the safety of different doses of MK-4002 and how well people tolerate them. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MK-4002
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
12 sitesin 3 countries
Study dates
13 Apr 2020to 31 Dec 2026
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

Major Inclusion Criteria:

  1. Patients ≥18 years of age at the time of signing informed consent
  2. Documented RRMM for which no standard therapy options are anticipated to result in a durable remission. Relapse defined as progressive disease after initial response (minimal response [MR] or better) to previous treatment, more than 60 days after cessation of last treatment. Refractory disease defined as <25% reduction in M protein or progression of disease during treatment or within 60 days after cessation of treatment.
  3. Received at least 3 prior therapies (including proteasome inhibitor, immune modulatory drug, and an anti-CD38 antibody; patients should not be a candidate for or be intolerant of all established therapies known to provide clinical benefit in multiple myeloma).
  4. Measurable disease defined as at least one of the following:
  5. Serum M-protein ≥0.5 g/dL
  6. Urine M-protein ≥200 mg/24 hours
  7. Serum free light chain (FLC) assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65)
  8. Resolved acute effects of any prior therapy to baseline severity or Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade ≤1.

Major Exclusion Criteria:

  1. Plasma cell leukemia; non-secretory myeloma (e.g., solitary plasmacytoma)
  2. Patients with only extramedullary relapse of multiple myeloma who do not meet requirement for measurable disease.
  3. Prior autologous peripheral stem cell transplant or prior autologous bone marrow transplantation within <90 days of the start of study
  4. Prior allogeneic stem cell transplantation or solid organ transplantation within 12 months of Screening. However, any patient receiving immunosuppressive medication will be excluded.
  5. History of or known or suspected autoimmune disease (exception(s): patients with vitiligo, resolved childhood atopic dermatitis, hypothyroidism, or hyperthyroidism that is clinically euthyroid at Screening are allowed). Other exceptions may be allowed following discussion with the Sponsor Medical Monitor for patients who have not received any treatment for their autoimmune disorder in the past 3 years
  6. Second primary malignancy that has not been in remission for greater than 3 years. Exceptions that do not require a 3-year remission: non-melanoma skin cancer, resected melanoma in situ, in situ cervical cancer, adequately treated Stage I cancer from which the subject is currently in remission and has been in remission for ≥2 years, low-risk prostate cancer with Gleason score <7 and prostate-specific antigen <10 ng/mL

Trial locations and contacts

12 sites in 3 countries.

12 sites in 3 countries

United States8 sites

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14263

  • The University of Kansas Cancer Center

    Fairway, Kansas, 66205

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • UC San Diego Moores Cancer Center

    La Jolla, California, 92093

  • Mayo Clinic Arizona

    Phoenix, Arizona, 85054

  • OHSU

    Portland, Oregon, 97239

  • University of Rochester James P Wilmot Cancer Institute

    Rochester, New York, 14642

  • University of Washington - Seattle Cancer Center Alliance

    Seattle, Washington, 98109

Other trials in United States

France2 sites

  • Centre Hospitalier Universitaire De Nantes

    Nantes, 44093

  • Centre Hospitalier Universitaire de Poitiers

    Poitiers, 86021

Other trials in France

Spain2 sites

  • Josep Carreras Leukaemia Research Institute

    Barcelona, 08916

  • Hospital Universitario Fundacion Jimenez Diaz (UAM-FJD)

    Madrid, 28040

Other trials in Spain

About this study

Official title: A Phase 1 Open-label, Multicenter, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of HPN217 in Patients With Relapsed/Refractory Multiple Myeloma

Researchers want to learn if MK-4002 (also known as HPN217) can treat relapsed or refractory multiple myeloma (RRMM). The goals of this study are to learn about the safety of different doses of MK-4002 and how well people tolerate them. Researchers also want to learn what happens to different doses of MK-4002 in a person's body over time.

Being tested
MK-4002
Medical subject headings
Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-4002Drug

    Also called HPN217

    IV infusion

Study groups in NCT04184050
Study groupRoleWhat they receive
MK-4002 monotherapy dose escalationExperimentalMK-4002 is intravenously (IV) administered once weekly in escalating doses.
Receives: Drug: MK-4002
MK-4002 dose escalation with extended dosing intervalsExperimentalMK-4002 is IV administered once every 2 weeks.
Receives: Drug: MK-4002

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants with Treatment-emergent Adverse Events (TEAEs)

    An adverse event (AE) is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. A TEAE is an adverse event that occurs on or after the first dose of study treatment. The number of participants with TEAEs graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (American Society for Transplant and Cellular Therapy [ASTCT] grading criteria for cytokine release syndrome [CRS] and immune effector cell-associated neurotoxicity syndrome [ICANS]) will be reported.

    Measured: Up to ~6 years

  2. Number of Participants Who Discontinued Study Treatment Due to an AE

    An AE is defined as any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinue study treatment due to an AE will be reported.

    Measured: Up to ~6 years

  3. Number of Participants with Dose-limiting toxicities (DLT)

    A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the CTCAE 5.0 version for all AEs except CRS and ICANS, which will be graded according to ASTCT. The number of participants who experience a DLT will be reported.

    Measured: Up to 35 days in Cycle 1

  4. Single Dose Maximum Serum Concentration (Cmax) of MK-4002

    Blood samples collected at designated time points will be used to determine the Cmax of MK-4002 after a single dose.

    Measured: At designated timepoints (up to ~6 years)

  5. Single Dose Time to Maximum Concentration (Tmax) of MK-4002

    Blood samples collected at designated time points will be used to determine the Tmax of MK-4002 after a single dose.

    Measured: At designated timepoints (up to ~6 years)

  6. Area Under the Single Dose Concentration-time Curve Over the Dosing Interval τ (AUCsd,τ) of MK-4002

    Blood samples collected at designated time points will be used to determine the AUCsd,τ of MK-4002.

    Measured: At designated timepoints (up to ~6 years)

  7. Single Dose Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) of MK-4002

    Blood samples collected at designated time points will be used to determine the AUCinf after a single dose of MK-4002.

    Measured: At designated timepoints (up to ~6 years)

  8. Single Dose Terminal Elimination Half-life (t1/2) of MK-4002

    Blood samples collected at designated time points will be used to determine the t1/2 after a single dose of MK-4002.

    Measured: At designated timepoints (up to ~6 years)

  9. Single Dose Clearance (CL) of MK-4002

    Blood samples collected at designated time points will be used to determine the CL after a single dose of MK-4002.

    Measured: At designated timepoints (up to ~6 years)

  10. Multiple Dose Maximum Concentration at Steady State (Css,max) of MK-4002

    Blood samples collected at designated time points will be used to determine the Css,max of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

  11. Multiple Dose Time to Maximum Concentration at Steady State (Tss,max) of MK-4002

    Blood samples collected at designated time points will be used to determine the Tss,max of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

  12. Mutiple Dose Area Under the Steady State Concentration-time Curve Over the Dosing Interval τ (AUCss,τ) of MK-4002

    Blood samples collected at designated time points will be used to determine the (AUCss,τ) of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

  13. Multiple Dose Terminal Elimination Half-life (t1/2) of MK-4002

    Blood samples collected at designated time points will be used to determine the t1/2 of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

  14. Multiple Dose Minimum Concentration at Steady State (Css,min) of MK-4002

    Blood samples collected at designated time points will be used to determine the Css,min of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

  15. Multiple Dose Clearance (CL)

    Blood samples collected at designated time points will be used to determine the CL of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

  16. Multiple Dose Volume of Distribution at Steady State (Vss) of MK-4002

    Blood samples collected at designated time points will be used to determine the Vss of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

  17. Multiple Dose Accumulation Ratio (AUCss,τ/AUCsd,τ) of MK-4002

    Blood samples collected at designated time points will be used to determine the (AUCss,τ/AUCsd,τ) of MK-4002. This outcome will be analyzed only if steady state is achieved, and data are available.

    Measured: At designated timepoints (up to ~6 years)

Secondary outcomes (9)

  1. Best Overall Response Rate (BOR)

    BOR is defined as the participant's best disease response assessed during the study. BOR will be based on assessments collected after the first dose of study drug until disease progression is documented.

    Measured: Up to ~6 years

  2. Overall Response rate (ORR)

    ORR is defined as the percentage of the participants with either a stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) according to the International Myeloma Working Group (IMWG) Response Criteria. CR = negative immunofixation of serum and urine AND <5% plasma cells in the bone marrow; sCR = CR plus normal serum free light-chain (FLC) assay ratio and absence of clonal plasma cells in bone marrow; VGPR = serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hr; PR = ≥50% reduction of serum M- protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The percentage of participants who experience CR or PR will be presented.

    Measured: Up to ~6 years

  3. Progression-free Survival (PFS)

    PFS is defined as the time from first dose of study drug to documented disease progression or death due to any cause, whichever occurs first.

    Measured: Up to ~6 years

  4. Overall Survival (OS)

    OS is defined as the time from first dose of study drug to death due to any cause.

    Measured: Up to ~6 years

  5. Duration of Response (DOR)

    DOR is defined as the time from the first observed response observed response (sCR, CR, VGPR, or PR) to documented disease progression or death due to any cause. CR = negative immunofixation of serum and urine AND <5% plasma cells in the bone marrow; sCR = CR plus normal serum free light-chain (FLC) assay ratio and absence of clonal plasma cells in bone marrow; VGPR = serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hr; PR = ≥50% reduction of serum M- protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. DOR as assessed by investigator according to IMWG response criteria will be presented.

    Measured: Up to ~6 years

  6. Time to Response (TTR)

    TTR is defined as the time from first dose of study drug to the first observed response response (sCR, CR, VGPR, or PR). CR = negative immunofixation of serum and urine AND <5% plasma cells in the bone marrow; sCR = CR plus normal serum free light-chain (FLC) assay ratio and absence of clonal plasma cells in bone marrow; VGPR = serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein plus urine M-protein <100 mg/24 hr; PR = ≥50% reduction of serum M- protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. TTR as assessed by investigator according to IMWG response criteria will be presented.

    Measured: Up to ~6 years

  7. Number of Participants with Anti-drug Antibodies (ADAs) against MK-4002

    Blood samples collected at designated time points will be used to determine the ADA response against MK-4002. The number of ADAs will be presented.

    Measured: At designated timepoints (up to ~6 years)

  8. Titers of ADAs against MK-4002

    Blood samples collected at designated time points will be used to determine the titers of ADAs against MK-4002.

    Measured: At designated timepoints (up to ~6 years)

  9. Percentage of Participants Who are Minimal Residual Disease (MRD) Negative

    Bone marrow samples will be used to determine the MRD negative. MRD is defined as the percentage of patients who achieve an sCR or CR who meet MRD Criteria for Sequencing MRD-negative rate at 10^5 nucleated cells threshold and at 10^6 nucleated cells threshold. CR = negative immunofixation of serum and urine AND <5% plasma cells in the bone marrow; sCR = stringent complete response. Sequencing MRD-negative is the absence of clonal plasma cells by next-generation sequencing (NGS) on bone marrow aspirate in which presence of a clone is defined as less than 2 identical sequencing reads obtained after deoxyribonucleic acid (DNA) sequencing of bone marrow aspirates using the LymphoSIGHT platform (or validated equivalent method).

    Measured: At designated timepoints (up to ~6 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Dec 2019
  2. Study start13 Apr 2020
  3. Primary completion31 Dec 2026 (estimated)
  4. Study completion31 Dec 2026 (estimated)

Resources

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
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04184050
Sponsor's protocol ID
HPN217-3001
Other IDs
U1111-1261-6031, MK-4002-001, 2024-515582-33-00, 2019-004793-26, 2019
Status last verified
Dec 2025
First submitted
27 Nov 2019
Last updated
5 Dec 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

Publications

  • Madan S, Costello C, Lipe B, Cowan AJ, Medvedova E, Hillengass J, Bergsagel PL, Leleu X, Touzeau C, Morillo D, Oriol A, Mawad R, Schade H, Yaron Y, Ng PP, Anand B, Akhtar R, Abdallah AO. MK-4002, a B-cell maturation antigen-targeting T-cell engager, in relapsed or refractory multiple myeloma: a first-in-human, open-label, phase 1 study. Lancet Haematol. 2026 Oct 6:S2352-3026(26)00228-0. doi: 10.1016/S2352-3026(26)00228-0. Online ahead of print.

    PubMed 42838070

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-4002 in people with Multiple Myeloma in Relapse and Multiple Myeloma, run by Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA) at 12 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

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: under way, not looking for participants, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, France, Spain. 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?

This study is still under way. Results are not available in the source record yet.

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 with Treatment-emergent Adverse Events (TEAEs) (time frame: Up to ~6 years). The study lists 17 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04184050, which also lists 1 linked publication.

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 5 Dec 2025.

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