Clinical trial NCT04184050: Study of HPN217 in Participants With Relapsed/Refractory Multiple Myeloma MK-4002 (MK-4002-001)
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Multiple Myeloma in Relapse
Multiple Myeloma
Multiple Myeloma of Bone
Multiple Myeloma With Failed Remission
Lead sponsor: Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Sponsor class: INDUSTRY
First posted: 2019-12-03
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to ~4 years
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to ~4 years
measure: Number of Participants with Dose-limiting toxicities (DLT)
timeFrame: Up to ~4 years
measure: Single Dose Maximum Serum Concentration (Cmax) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Single Dose Time to Maximum Concentration (Tmax) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Area Under the Single Dose Concentration-time Curve Over the Dosing Interval τ (AUCsd,τ) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Single Dose Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Single Dose Terminal Elimination Half-life (t1/2) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Single Dose Clearance (CL) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Multiple Dose Maximum Concentration at Steady State (Css,max) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Multiple Dose Time to Maximum Concentration at Steady State (Tss,max) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Mutiple Dose Area Under the Steady State Concentration-time Curve Over the Dosing Interval τ (AUCss,τ) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Multiple Dose Terminal Elimination Half-life (t1/2) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Multiple Dose Minimum Concentration at Steady State (Css,min) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Multiple Dose Clearance (CL)
timeFrame: At designated timepoints (up to ~4 years)
measure: Multiple Dose Volume of Distribution at Steady State (Vss) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Multiple Dose Accumulation Ratio (AUCss,τ/AUCsd,τ) of MK-4002
timeFrame: At designated timepoints (up to ~4 years)
Secondary outcomes:
measure: Best Overall Response Rate (BOR)
timeFrame: Up to ~4 years
measure: Overall Response rate (ORR)
timeFrame: Up to ~4 years
measure: Progression-free Survival (PFS)
timeFrame: Up to ~4 years
measure: Overall Survival (OS)
timeFrame: Up to ~ 4 years
measure: Duration of Response (DOR)
timeFrame: Up to ~4 years
measure: Time to Response (TTR)
timeFrame: Up to ~4 years
measure: Number of Participants with Anti-drug Antibodies (ADAs) against MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Titers of ADAs against MK-4002
timeFrame: At designated timepoints (up to ~4 years)
measure: Percentage of Participants Who are Minimal Residual Disease (MRD) Negative
timeFrame: At designated timepoints (up to ~4 years)
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego Moores Cancer Center
state: California
city: Fairway
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: Rochester
country: United States
facility: University of Rochester James P Wilmot Cancer Institute
state: New York
city: Portland
country: United States
facility: OHSU
state: Oregon
city: Seattle
country: United States
facility: University of Washington - Seattle Cancer Center Alliance
state: Washington
city: Nantes
country: France
facility: Centre Hospitalier Universitaire De Nantes
city: Poitiers
country: France
facility: Centre Hospitalier Universitaire de Poitiers
city: Barcelona
country: Spain
facility: Josep Carreras Leukaemia Research Institute
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz (UAM-FJD)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: