Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT04184050

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Multiple Myeloma in Relapse Blood Protein Disorders Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Multiple Myeloma Multiple Myeloma With Failed Remission Multiple Myeloma of Bone Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Centre Hospitalier Universitaire De Nantes, Nantes, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Major Inclusion Criteria:

  • Patients ≥18 years of age at the time of signing informed consent
  • 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.
  • 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).
  • Measurable disease defined as at least one of the following:
  • Serum M-protein ≥0.5 g/dL
  • Urine M-protein ≥200 mg/24 hours
  • 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)
  • 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:

  • Plasma cell leukemia; non-secretory myeloma (e.g., solitary plasmacytoma)
  • Patients with only extramedullary relapse of multiple myeloma who do not meet requirement for measurable disease.
  • Prior autologous peripheral stem cell transplant or prior autologous bone marrow transplantation within <90 days of the start of study
  • Prior allogeneic stem cell transplantation or solid organ transplantation within 12 months of Screening. However, any patient receiving immunosuppressive medication will be excluded.
  • 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
  • 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

Treatment and study plan

MK-4002

Drug

IV infusion

Other names: HPN217

Primary outcomes

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

    Time frame: Up to ~6 years

    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.

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

    Time frame: Up to ~6 years

    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.

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

    Time frame: Up to 35 days in Cycle 1

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

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

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

    Time frame: At designated timepoints (up to ~6 years)

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

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

    Time frame: At designated timepoints (up to ~6 years)

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

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

    Time frame: At designated timepoints (up to ~6 years)

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

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

    Time frame: At designated timepoints (up to ~6 years)

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

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

    Time frame: At designated timepoints (up to ~6 years)

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

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

  15. Multiple Dose Clearance (CL)

    Time frame: At designated timepoints (up to ~6 years)

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

Secondary outcomes

  1. Best Overall Response Rate (BOR)

    Time frame: Up to ~6 years

    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.

  2. Overall Response rate (ORR)

    Time frame: Up to ~6 years

    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.

  3. Progression-free Survival (PFS)

    Time frame: Up to ~6 years

    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.

  4. Overall Survival (OS)

    Time frame: Up to ~6 years

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

  5. Duration of Response (DOR)

    Time frame: Up to ~6 years

    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.

  6. Time to Response (TTR)

    Time frame: Up to ~6 years

    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.

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

    Time frame: At designated timepoints (up to ~6 years)

    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.

  8. Titers of ADAs against MK-4002

    Time frame: At designated timepoints (up to ~6 years)

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

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

    Time frame: At designated timepoints (up to ~6 years)

    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).

Sponsors and collaborators

Lead sponsor

Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2026
Study completion
2026
First posted
Dec 3, 2019
Registry last updated
Dec 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.