Clinical Trials /

First in Human Dose Escalation and Expansion Study With M3258 in Combination With Dexamethasone

NCT04075721

Description:

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

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First in Human Dose Escalation and Expansion Study With M3258 in Combination With Dexamethasone
  • Official Title: A Phase I Open Label First in Human Dose Escalation and Expansion Study of the Immunoproteasome Inhibitor M3258 in Combination With Dexamethasone in Participants With Relapsed Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: MS201814_0010
  • SECONDARY ID: 2019-000947-28
  • NCT ID: NCT04075721

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
M3258Part A (Dose Escalation): M3258
DexamethasonePart A (Dose Escalation): M3258

Purpose

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

Trial Arms

NameTypeDescriptionInterventions
Part A (Dose Escalation): M3258Experimental
  • M3258
  • Dexamethasone
Part B (Dose Expansion): M3258Experimental
  • M3258
  • Dexamethasone

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

          -  Other protocol defined exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: 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)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Part A:Maximum Observed Plasma Concentration (Cmax) of M3258
Time Frame:Day 1 Cycle 1: Pre-dose upto 24 hours post-dose, Day 15 Cycle 1: Pre-dose upto 8 hours post-dose (each Cycle is of 28 days)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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 15 Cycle 1: Pre-dose upto 24 hours post-dose (each Cycle is of 28 days)
Safety Issue:
Description:
Measure: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 15 of Cycle 1; Pre-dose on Day 2 of Cycle 1 (each cycle is of 28 days)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Part A: Overall Response (OR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria
Time Frame:up to 556 days
Safety Issue:
Description:
Measure:Part A: Duration of Response (DOR) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria
Time Frame:up to 556 days
Safety Issue:
Description:
Measure:Part A: Time to Response as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria
Time Frame:up to 556 days
Safety Issue:
Description:
Measure:Part B: Progression-Free Survival (PFS) as Assessed by Investigator Using International Myeloma Working Group (IMWG) Criteria
Time Frame:up to 556 days
Safety Issue:
Description:
Measure:Part B: Overall Survival Time According to International Myeloma Working Group (IMWG) Criteria
Time Frame:up to 556 days
Safety Issue:
Description:
Measure:Part B: Number of Participants With Treatment-Emergent Serious Adverse Events (TESAEs)
Time Frame:Day 1 upto 30 days post-last dose (assessed upto maximum 556 days)
Safety Issue:
Description:
Measure:Part B: Occurrences of Treatment-Emergent Adverse Event (TEAEs) and Treatment-Related Adverse Event (TRAEs) in Participants Receiving M3258
Time Frame:Day 1 upto 30 days post-last dose (assessed upto maximum 556 days)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • M3258
  • Dexamethasone
  • Pharmacokinetics
  • Relapsed Refractory Multiple Myeloma

Last Updated

January 28, 2020