Multiple Myeloma, Multiple Myeloma in Relapse, Multiple Myeloma of Bone, Multiple Myeloma With Failed Remission
Conditions
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.
Interventions
DRUGMK-4002
IV infusion
Sponsors
Harpoon Therapeutics, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | 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. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | 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. |
| Number of Participants with Dose-limiting toxicities (DLT) | 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. |
| Single Dose Maximum Serum Concentration (Cmax) of MK-4002 | 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. |
| Single Dose Time to Maximum Concentration (Tmax) of MK-4002 | 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. |
| Area Under the Single Dose Concentration-time Curve Over the Dosing Interval τ (AUCsd,τ) of MK-4002 | 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. |
| Single Dose Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) of MK-4002 | 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. |
| Single Dose Terminal Elimination Half-life (t1/2) of MK-4002 | 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. |
| Single Dose Clearance (CL) of MK-4002 | 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. |
| Multiple Dose Maximum Concentration at Steady State (Css,max) of MK-4002 | 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. |
| Multiple Dose Time to Maximum Concentration at Steady State (Tss,max) of MK-4002 | 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. |
| Mutiple Dose Area Under the Steady State Concentration-time Curve Over the Dosing Interval τ (AUCss,τ) of MK-4002 | 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. |
| Multiple Dose Terminal Elimination Half-life (t1/2) of MK-4002 | 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. |
| Multiple Dose Minimum Concentration at Steady State (Css,min) of MK-4002 | 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. |
| Multiple Dose Clearance (CL) | 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. |
| Multiple Dose Volume of Distribution at Steady State (Vss) of MK-4002 | 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. |
| Multiple Dose Accumulation Ratio (AUCss,τ/AUCsd,τ) of MK-4002 | 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
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (BOR) | 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. |
| Overall Response rate (ORR) | 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. |
| Progression-free Survival (PFS) | 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. |
| Overall Survival (OS) | Up to ~6 years | OS is defined as the time from first dose of study drug to death due to any cause. |
| Duration of Response (DOR) | 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. |
| Time to Response (TTR) | 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. |
| Number of Participants with Anti-drug Antibodies (ADAs) against MK-4002 | 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. |
| Titers of ADAs against MK-4002 | 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. |
| Percentage of Participants Who are Minimal Residual Disease (MRD) Negative | 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). |
Countries
France, Spain, United States
Outcome results
None listed