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

NCT04184050 | Active Not Recruiting Phase 1 FDA Drug

• 5 other identifiers: HPN217-3001U1111-1261-6031MK-4002-0012024-515582-33-002019-004793-26
• Study Type: interventional
• Target: 100
• Locations: 3 countries
• Sites: 12

Brief 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. Researchers also want to learn what happens to different doses of MK-4002 in a person's body over time.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma; Multiple Myeloma of Bone; Multiple Myeloma With Failed Remission

Outcome Measures

Primary Outcomes (17)

• 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 Outcomes (9)

• Best Overall Response Rate (BOR)

  Up to ~6 years

• Overall Response rate (ORR)

  Up to ~6 years

• Progression-free Survival (PFS)

  Up to ~6 years

• Overall Survival (OS)

  Up to ~6 years

• Duration of Response (DOR)

  Up to ~6 years

Study Arms (2)

MK-4002 monotherapy dose escalation

EXPERIMENTAL

MK-4002 is intravenously (IV) administered once weekly in escalating doses.

Drug: MK-4002

MK-4002 dose escalation with extended dosing intervals

EXPERIMENTAL

MK-4002 is IV administered once every 2 weeks.

Drug: MK-4002

Interventions

MK-4002 DRUG

IV infusion

Also known as: HPN217

MK-4002 dose escalation with extended dosing intervals; MK-4002 monotherapy dose escalation

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (12)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

The University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

Location

University of Rochester James P Wilmot Cancer Institute

Rochester, New York, 14642, United States

Location

OHSU

Portland, Oregon, 97239, United States

Location

University of Washington - Seattle Cancer Center Alliance

Seattle, Washington, 98109, United States

Location

Centre Hospitalier Universitaire De Nantes

Nantes, 44093, France

Location

Centre Hospitalier Universitaire de Poitiers

Poitiers, 86021, France

Location

Josep Carreras Leukaemia Research Institute

Barcelona, 08916, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz (UAM-FJD)

Madrid, 28040, Spain

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

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: November 27, 2019
• First Posted: December 3, 2019
• Study Start: April 13, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

US (8); ES (2); FR (2)