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First in Human Dose Escalation of M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone

Primary Purpose

Multiple Myeloma

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

M3258

M3258 20 mg

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring M3258, Dexamethasone, Pharmacokinetics, Relapsed Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Colorado Blood Cancer Institute
Georgetown University Medical Center- Research Parent
Hackensack University Medical Center
Sarah Cannon Research Institute
Centre Hospitalier Regional Universitaire de Lille
CHU de Nantes
CHU de Poitiers

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

M3258 10 mg QD

M3258 10 mg Twice per Week

M3258 20 mg Twice per Week

Arm Description

Outcomes

Primary Outcome Measures

Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

DLT: any of adverse events (AEs), assessed by Investigator and/Sponsor at any dose, regimen, and judged not to be related to underlying disease/any previous/concomitant medication/concurrent condition during first cycle of study treatment. DLT was confirmed by Safety Monitoring Committee. DLTs: Grade (Gr) greater than/equal to (>=) 3 nonhematologic AE with exception of: Single laboratory values out of abnormal range; Gr3 diarrhea persisting less than or equal to [<=] 72 hour (hr); Nausea and vomiting <= 72 hr; Transient Gr3 fatigue, local reactions, flu-like symptoms <= 72 hr; Gr3 nonrecurrent skin toxicity; Asymptomatic Gr >= 3 lipase/amylase elevation. Any Gr >= 4 hematologic AE: Gr >= 3 febrile neutropenia with Absolute Neutrophil Count (ANC) <1000 per cube millimeter and temperature of >38.3 Celsius (°C); Gr >= 3 thrombocytopenia; Gr4 thrombocytopenia lasting >7 days.

Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)

Adverse Event (AE): any untoward medical occurrence in a participant administered with a study drug, which does not necessarily have a causal relationship with this treatment. TEAEs: events that started from first dose of study intervention to 30 days after end of study intervention, or the cutoff date, whichever occurred first. TEAEs included both serious TEAEs (Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect) and non-serious TEAEs. TRAEs are defined as those AEs which are reasonably related to the study intervention.

Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) Outside of Dose-Limiting Toxicity (DLT) Period That Safety Monitoring Committee Deems Relevant for Determination of the Maximum Tolerated Dose

Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula

12-lead ECG were recorded after the participants have rested for at least 15 minutes in supine position. Change from baseline in 12-Lead ECG findings that is QT interval - Fridericia's correction formula at pre-dose on Cycle 2 Day 1 were reported.

Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with shifts in score from baseline value vs worst post-baseline value (that is [i.e.] highest score).

Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment

Laboratory parameters included hematology, chemistry, and coagulation. Number of participants with shifts from baseline (Grade <3) to >= Grade 3 were reported as per NCI-CTCAE, v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death.

Secondary Outcome Measures

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase

The number of participants with treatment-emergent changes from baseline in increased Body Temperature (degree Celsius [°C]) were reported by using criteria: Baseline temperature (temp.) less than (<) 37°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C and greater than or equal to (>=)3°C; Baseline temp. 37 - <38°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C and >=3°C; Baseline temp. 38 - <39°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C and >=3°C; Baseline temp. 39-<40°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C and >=3°C; Baseline temp. >=40°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C and >=3°C.

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease

The number of participants with treatment-emergent changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) Systolic Blood Pressure (SBP) and diastolic blood pressure (DBP) (millimeter of mercury [mmHg]) were reported by using criteria: Ic./Dc. BS SBP/DBP <140/<90 mmHg, on maximal treatment (TR) change =<20 mmHg, >20 - =<40 mmHg and >40 mmHg; Ic./Dc. BS SBP/DBP >=140/>=90 mmHg, on maximal TR change =<20 mmHg, >20 - =<40 mmHg and >40 mmHg.

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease

The number of participants with treatment-emergent changes from baseline in Increase (Ic.)/Decrease (Dc.) maximal Respiration Rate (RR) were reported by using criteria: Ic./Dc. BS RR <20 breaths per minute (breaths/min), on TR change (ch) =<5 breaths/min, >5 - =<10 breaths/min and >10 breaths/min. Ic./Dc. BS RR >=20 breaths/min, on TR ch =<5 breaths/min, >5 - =<10 breaths/min and >10 breaths/min.

Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Cmax was obtained directly from the concentration versus time curve. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (>) 2 in which a measurement of greater than (>) lower limit of quantification (LLOQ) represents a valid measurement.

Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Cmax was obtained directly from the concentration versus time curve.

Part A: Single Dose: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC0-t) of M3258

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (>) 2 in which a measurement of greater than (>) lower limit of quantification (LLOQ) represents a valid measurement.

Part A: Single Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Area under the plasma concentration versus time curve from time zero to 24 hours post dosing for M3258. Single dose PK data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (>) 2 in which a measurement of greater than (>) lower limit of quantification (LLOQ) represents a valid measurement.

Part A: Multiple Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Area under the plasma concentration versus time curve from time zero to 24 hours post dosing for M3258.

Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1

Ratio to baseline was calculated dividing post-baseline measurements by the baseline measurement. Single dose Pd data on Day 1 were summarized by dose level, such that all 10 mg arms were combined as descriptive statistics of PK were only calculated for N greater than (>) 2 in which a measurement of greater than (>) lower limit of quantification (LLOQ) represents a valid measurement.

Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)

Ratio to baseline was calculated dividing post-baseline measurements by the baseline measurement.

Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis

Change from baseline in serum monoclonal (M)-protein level was measured by using electrophoresis at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis

Change from baseline in urine M-protein level was measured by using electrophoresis at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Part A: Change From Baseline in Free Light Chain Ratio

Change from baseline in free light chain ratio was reported at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

OR is defined as a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on the IMWG Criteria: sCR: CR (negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow); normal free light chain (FLC) ratio and no clonal cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis/>= 90% reduction in serum M-protein and urine M-protein level < 100 mg/24 hours; PR: >= 50% reduction of serum M-Protein and reduction in urinary M-protein by >= 90%/to < 200 mg/24 hours. In addition to the above, if present at baseline a >= 50% reduction in the size of soft tissue plasmacytomas is also required.

Duration of Response (DoR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

DOR was defined participants with confirmed response, as time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to date of first documentation of progression disease (PD)/death due to any cause, whichever occurred first. CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. PR: >= 50% reduction of serum M-Protein and reduction in urinary M-protein by >= 90%/to < 200 mg/24 hours. In addition to the above, if present at baseline a >= 50% reduction in the size of soft tissue plasmacytomas is also required. PD: >= 25% increase from lowest response value in serum. Development of new or increased size of existing bone lesions or soft tissue plasmacytomas. Hypercalcemia attributed to the plasma cell proliferative disorder.

Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

Time to response was defined as the time from the first dose of M3258 to the documentation of first response (Complete Response [CR] or Partial Response [PR]). CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5% plasma cells in bone marrow. PR: >= 50% reduction of serum M-Protein and reduction in urinary M-protein by >= 90% or to < 200 mg/24 hours. In addition to the above, if present at baseline a >= 50% reduction in the size of soft tissue plasmacytomas is also required.

Full Information

NCT ID

NCT04075721

First Posted

August 29, 2019

Last Updated

June 9, 2022

Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

1. Study Identification

Unique Protocol Identification Number

NCT04075721

Brief Title

First in Human Dose Escalation of M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2022

Overall Recruitment Status

Terminated

Why Stopped

The study was early discontinued due to lack of participant enrollment.

Study Start Date

September 26, 2019 (Actual)

Primary Completion Date

April 1, 2021 (Actual)

Study Completion Date

April 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

EMD Serono Research & Development Institute, Inc.

Collaborators

Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study was to determine the safety, tolerability, pharmacokinetics, pharmacodynamics and early efficacy signs of M3258 as a single agent and co-administered with dexamethasone in participants with Relapsed Refractory Multiple Myeloma (RRMM).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Myeloma

Keywords

M3258, Dexamethasone, Pharmacokinetics, Relapsed Refractory Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

10 (Actual)

8. Arms, Groups, and Interventions

Arm Title

M3258 10 mg QD

Arm Type

Experimental

Arm Title

M3258 10 mg Twice per Week

Arm Type

Experimental

Arm Title

M3258 20 mg Twice per Week

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

M3258

Intervention Description

Participants received M3258 at a dose of 10 milligrams (mg) orally, once daily (QD) or twice per week on Day 1 and Day 4 until disease progression.

Intervention Type

Drug

Intervention Name(s)

M3258 20 mg

Intervention Description

Participants received M3258 at a dose of 20 mg orally, twice per week on Day 1 and Day 4 until disease progression.

Primary Outcome Measure Information:

Title

Part A: Number of Participants With Dose-Limiting Toxicities (DLTs) as Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0

Description

Time Frame

Day 1 up to Day 28

Title

Part A: Number of Participants With Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs)

Description

Time Frame

Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Title

Description

Time Frame

Day 29 up to 20.1 weeks

Title

Part A: Change From Baseline in 12-lead Electrocardiogram (ECG) Findings: QT Interval - Fridericia's Correction Formula

Description

Time Frame

Cycle 1 Day 1 pre-dose (Baseline), pre-dose on Cycle 2 Day 1 (each Cycle is of 28 days)

Title

Part A: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

Description

Time Frame

Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Title

Number of Participants With Shift From Baseline Grade Less Than (<) 3 in Clinical Laboratory Parameters to Grade Greater Than or Equal to (>=) 3 on Treatment

Description

Time Frame

Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Secondary Outcome Measure Information:

Title

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Body Temperature Increase

Description

Time Frame

Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Title

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease

Description

Time Frame

Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Title

Part A: Number of Participants With Treatment-Emergent Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease

Description

Time Frame

Time from first treatment up to 30 days after end of study intervention (assessed up to 24.3 weeks)

Title

Part A: Single Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Description

Time Frame

Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)

Title

Part A: Mutilple Dose: Maximum Observed Plasma Concentration (Cmax) of M3258

Description

Cmax was obtained directly from the concentration versus time curve.

Time Frame

Cycle 1 Day 8 or Cycle 1 Day 15: Pre-dose 1, 2, 3, 4, 5, 6, and 8 hours post-dose (each Cycle is of 28 days)

Title

Part A: Single Dose: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero to Last Sampling Time (AUC0-t) of M3258

Description

Time Frame

Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)

Title

Part A: Single Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Description

Time Frame

Cycle 1 Day 1: Pre-dose 1, 2, 3, 4, 5, 6, 8 and 24 hours post-dose (each Cycle is of 28 days)

Title

Part A: Multiple Dose: Area Under Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24) of M3258

Description

Area under the plasma concentration versus time curve from time zero to 24 hours post dosing for M3258.

Time Frame

Cycle 1 Day 8 or Cycle 1 Day 15: Pre-dose 1, 2, 3, 4, 5, 6, and 8 hours post-dose (each Cycle is of 28 days)

Title

Part A: Single Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 1

Description

Time Frame

Baseline (Pre-dose), 2, 6 and 24 hours post-dose on Cycle 1 Day 1 (each Cycle is of 28 days)

Title

Part A: Multiple Dose: Ratio to Baseline in Large Multifunctional Protease 7 (LMP7) Activity at Cycle 1 Day 8 (or Day 15)

Description

Ratio to baseline was calculated dividing post-baseline measurements by the baseline measurement.

Time Frame

Cycle 1 Day 1 pre-dose (Baseline), Pre-dose, 2 and 6 hours post-dose on Cycle 1 Day 8 (or Day 15) (each Cycle is of 28 days)

Title

Part A: Change From Baseline in Serum Monoclonal (M)-Protein Level Measured Using Electrophoresis

Description

Time Frame

Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)

Title

Part A: Change From Baseline in Urine M-protein Level Using Electrophoresis

Description

Change from baseline in urine M-protein level was measured by using electrophoresis at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Time Frame

Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)

Title

Part A: Change From Baseline in Free Light Chain Ratio

Description

Change from baseline in free light chain ratio was reported at Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention.

Time Frame

Baseline, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1 and end of study intervention (Week 20.1) (each Cycle is of 28 days)

Title

Part A: Number of Participants With Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

Description

Time Frame

Time from first dose of study treatment up to 18.2 months

Title

Duration of Response (DoR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

Description

Time Frame

Time from first documentation of objective response until date of first documentation of PD or death due to any cause, whichever occurred first, assessed up to 18.2 months

Title

Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria

Description

Time Frame

Time from the first dose of study treatment up to documentation of first response, assessed up to 18.2 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Responsible

Organizational Affiliation

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Official's Role

Study Director

Facility Information:

Facility Name

Colorado Blood Cancer Institute

City

Denver

State/Province

Colorado

ZIP/Postal Code

80218

Country

United States

Facility Name

Georgetown University Medical Center- Research Parent

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20007

Country

United States

Facility Name

Hackensack University Medical Center

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Sarah Cannon Research Institute

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Centre Hospitalier Regional Universitaire de Lille

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

CHU de Nantes

City

Nantes

ZIP/Postal Code

44093

Country

France

Facility Name

CHU de Poitiers

City

Vauvert

ZIP/Postal Code

30600

Country

France

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports 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 http://bit.ly/IPD21

Citations:

PubMed Identifier

34045234

Citation

Sanderson MP, Friese-Hamim M, Walter-Bausch G, Busch M, Gaus S, Musil D, Rohdich F, Zanelli U, Downey-Kopyscinski SL, Mitsiades CS, Schadt O, Klein M, Esdar C. M3258 Is a Selective Inhibitor of the Immunoproteasome Subunit LMP7 (beta5i) Delivering Efficacy in Multiple Myeloma Models. Mol Cancer Ther. 2021 Aug;20(8):1378-1387. doi: 10.1158/1535-7163.MCT-21-0005. Epub 2021 May 27.

Results Reference

result

Links:

URL

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201814_0010

Description

Trial Awareness and Transparency website

URL

https://medical.emdserono.com/en_US/home.html

Description

US Medical Information website, Medical Resources

Learn more about this trial

First in Human Dose Escalation of M3258 as a Single Agent and Expansion Study of M3258 in Combination With Dexamethasone

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