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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma With Failed Remission; Multiple Myeloma of Bone
• Intervention / Treatment: Drug: MK-4002

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • Centre Hospitalier Universitaire de Nantes
  • Poitiers, France, 86021
    • Centre Hospitalier Universitaire de Poitiers
• Spain
  • Barcelona, Spain, 08916
    • Josep Carreras Leukaemia Research Institute
  • Madrid, Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz (UAM-FJD)
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
  • Kansas
    • Fairway, Kansas, United States, 66205
      • The University of Kansas Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Comprehensive Cancer Center
    • Rochester, New York, United States, 14642
      • University of Rochester James P Wilmot Cancer Institute
  • Oregon
    • Portland, Oregon, United States, 97239
      • OHSU
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington - Seattle Cancer Center Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

   1. Serum M-protein ≥0.5 g/dL
   2. Urine M-protein ≥200 mg/24 hours
   3. 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)
5. 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

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MK-4002 monotherapy dose escalation; MK-4002 is intravenously (IV) administered once weekly in escalating doses.	Drug: MK-4002; IV infusion; Other Names: HPN217
Experimental: MK-4002 dose escalation with extended dosing intervals; MK-4002 is IV administered once every 2 weeks.	Drug: MK-4002; IV infusion; Other Names: HPN217

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to ~6 years
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.	Up to ~6 years
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.	Up to 35 days in Cycle 1
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to ~6 years
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.	Up to ~6 years
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.	Up to ~6 years
Overall Survival (OS)	OS is defined as the time from first dose of study drug to death due to any cause.	Up to ~6 years
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.	Up to ~6 years
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.	Up to ~6 years
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.	At designated timepoints (up to ~6 years)
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.	At designated timepoints (up to ~6 years)
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).	At designated timepoints (up to ~6 years)

Collaborators and Investigators

• Sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
• 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): April 13, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 27, 2019
• First Submitted That Met QC Criteria: November 29, 2019
• First Posted (Actual): December 3, 2019

Study Record Updates

• Last Update Posted (Estimated): December 5, 2025
• Last Update Submitted That Met QC Criteria: December 4, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma
• Other Study ID Numbers: HPN217-3001; U1111-1261-6031 (Registry Identifier: UTN); MK-4002-001 (Other Identifier: MSD); 2019-004793-26 (EudraCT Number); 2024-515582-33-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/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