First in Human Dose Escalation of M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone
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ClinicalTrials.gov Identifier: NCT04075721 |
Recruitment Status :
Terminated
(The study was discontinued given the changed therapeutic landscape, lack of recruitment and totality of the data collected so far.)
First Posted : September 3, 2019
Last Update Posted : May 12, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Multiple Myeloma | Drug: M3258 Drug: Dexamethasone | Phase 1 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 10 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | A Phase I Open Label First in Human Dose Escalation of the Immunoproteasome Inhibitor M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone in Participants With Relapsed Refractory Multiple Myeloma |
Actual Study Start Date : | September 26, 2019 |
Actual Primary Completion Date : | April 1, 2021 |
Actual Study Completion Date : | April 1, 2021 |

Arm | Intervention/treatment |
---|---|
Experimental: Part A (Dose Escalation): M3258 |
Drug: M3258
Participants will receive M3258 in a protocol-defined dose escalation scheme in Part A and M3258 at a dose and regimen defined and considered to be safe by safety monitoring committee (SMC) in Part B until disease progression. |
Experimental: Part B (Dose Expansion): M3258 |
Drug: M3258
Participants will receive M3258 in a protocol-defined dose escalation scheme in Part A and M3258 at a dose and regimen defined and considered to be safe by safety monitoring committee (SMC) in Part B until disease progression. Drug: Dexamethasone Participants will receive dexamethasone at a cumulative dose of 40 milligrams per week along with M3258 in Part B until disease progression. |
- Part A and Part B: Number of Participants with Dose-Limiting Toxicity (DLTs) [ Time Frame: Day 1 up to Day 28 of Treatment Cycle 1 (each cycle is of 28 days) ]
- Part A and Part B: Occurrences of Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs ) [ Time Frame: Day 1 upto 30 days post-last dose (assessed upto maximum 556 days) ]
- Part A:Number of Participants with Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLTs) Period [ Time Frame: Day 29 upto 30 days post-last dose (assessed upto maximum 528 days) ]
- Part A and Part B: Number of Participants With Treatment Emergent Changes From Baseline in Eastern Co-operative Oncology Group (ECOG) Performance Status, Vital Signs, Laboratory Parameters and 12-lead Electrocardiogram (ECG) Findings [ Time Frame: Day 1 upto 30 days post-last dose (assessed upto maximum 556 days) ]Number of participants with treatment emergent changes from baseline in ECOG performance status, vital signs, laboratory parameters and 12-lead ECG findings will be reported.
- Part B: Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part B: Duration of Response (DOR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part B: Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part B: Occurrence of Study Treatment-Emergent SAEs Including Deaths [ Time Frame: Day 1 upto 30 days post-last dose (assessed upto maximum 556 days) ]
- Part A:Maximum Observed Plasma Concentration (Cmax) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose upto 24 hours post-dose, Day 8 Cycle 1: Pre-dose upto 8 hours post-dose (each Cycle is of 28 days) ]
- Part A: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC 0-t) of M3258 [ Time Frame: Pre-dose upto 24 hours post-dose on Day 1 of Cycle 1 (each cycle is of 28 days) ]
- Part A: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose upto 24 hours post-dose, Day 8 Cycle 1: Pre-dose upto 8 hours post-dose (each Cycle is of 28 days) ]
- Part A: Change in Large Multifunctional Protease 7 (LMP7) Activity as Assessed by LMP7 Activity Assay [ Time Frame: Pre-dose, 2, 6 hours post-dose on Day 1 and Day 8 of Cycle 1; Pre-dose on Day 2 of Cycle 1 (each cycle is of 28 days) ]
- Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis [ Time Frame: Baseline (Cycle 1 Day 1), Day 1 of each 28-day treatment Cycle until end of study (assessed upto maximum 556 days) ]
- Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis [ Time Frame: Baseline (Cycle 1 Day 1), Day 1 of each 28-day treatment Cycle until end of study (assessed upto maximum 556 days) ]
- Part A: Change From Baseline in Free Light Chain Protein Level Using Electrophoresis [ Time Frame: Baseline (Cycle 1 Day 1), Day 1 of each 28-day treatment Cycle until end of study (assessed upto maximum 556 days) ]
- Part A: Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part A: Duration of Response (DOR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part A: Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part B: Progression-Free Survival (PFS) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part B: Overall Survival Time According to International Myeloma Working Group (IMWG) Criteria [ Time Frame: up to 556 days ]
- Part B: Maximum Observed Plasma Concentration (Cmax) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose, 1, 2, 3, 4, 5, and 6 and 24 hours Post-dose; Day 8 Cycle 1: pre-dose, 2, 4, and 6 hours post-dose (each cycle is of 28 days) ]
- Part B: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC 0-t) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose, 1, 2, 3, 4, 5, and 6 and 24 hours Post-dose (each cycle is of 28 days) ]
- Part B: Area Under the Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258 [ Time Frame: Day 1 Cycle 1: Pre-dose, 1, 2, 3, 4, 5, and 6 and 24 hours Post-dose; Day 8 Cycle 1: pre-dose, 2, 4, and 6 hours post-dose (each cycle is of 28 days) ]

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Participants having Eastern Co-operative Oncology Group (ECOG) Performance Status less than or equals to (<=) 1
- Adequate hematological, hepatic and renal function as defined in the protocol
- Participant must have measurable disease of Multiple Myeloma (MM) and received greater than (>) 3 prior lines of therapy for MM including a Proteasome Inhibitors (PI), an Immunomodulatory Imide Drug (IMiD) and an anti-CD38 mAb or who are refractory to at least PI agent (carfilzomib or bortezomib) and IMiD according to the International Myeloma Working Group (IMWG) criteria
- Participant must have documented evidence progressive disease as defined by the IMWG criteria either on or after their last regimen
- Other protocol defined inclusion criteria could apply
Exclusion Criteria:
- Any condition, including any uncontrolled disease state that in the Investigator's opinion constitutes an inappropriate risk or a contraindication for participation in the study or that could interfere with the study objectives, conduct, or evaluation.
- An active second malignancy or evidence of disease of cancer (other than MM) before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years).
- Cerebrovascular accident/stroke (< 6 months prior enrollment) or neurologic instability per clinical evaluation due to tumor involvement of the Central Nervous System
- Diagnosis of fever within 1 week prior to study intervention administration
- Part B: Participants planning to undergo a stem cell transplant should not be enrolled to reduce disease burden prior to transplant.
- Other protocol defined exclusion criteria could apply

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04075721
United States, Colorado | |
Colorado Blood Cancer Institute | |
Denver, Colorado, United States, 80218 | |
United States, District of Columbia | |
Georgetown University Medical Center- Research Parent | |
Washington, District of Columbia, United States, 20007 | |
United States, New Jersey | |
Hackensack University Medical Center | |
Hackensack, New Jersey, United States, 07601 | |
United States, Tennessee | |
Sarah Cannon Research Institute | |
Nashville, Tennessee, United States, 37203 | |
France | |
Centre Hospitalier Regional Universitaire de Lille | |
Lille, France, 59037 | |
CHU de Nantes | |
Nantes, France, 44093 | |
CHU de Poitiers | |
Vauvert, France, 30600 |
Study Director: | Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | EMD Serono Research & Development Institute, Inc. |
ClinicalTrials.gov Identifier: | NCT04075721 |
Other Study ID Numbers: |
MS201814_0010 2019-000947-28 ( EudraCT Number ) |
First Posted: | September 3, 2019 Key Record Dates |
Last Update Posted: | May 12, 2021 |
Last Verified: | May 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Plan Description: | Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
M3258 Dexamethasone Pharmacokinetics Relapsed Refractory Multiple Myeloma |
Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders |
Immune System Diseases Dexamethasone Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents |