Description:
The purpose of this study is 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).
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
MS201814_0010
- SECONDARY ID:
2019-000947-28
- NCT ID:
NCT04075721
Conditions
Interventions
Drug | Synonyms | Arms |
---|
M3258 | | Part A (Dose Escalation): M3258 |
Dexamethasone | | Part B (Dose Expansion): M3258 |
Purpose
The purpose of this study is 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).
Trial Arms
Name | Type | Description | Interventions |
---|
Part A (Dose Escalation): M3258 | Experimental | | |
Part B (Dose Expansion): M3258 | Experimental | | |
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | 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) |
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 8 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 8 Cycle 1: Pre-dose upto 8 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 8 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: 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Measure: | 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) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | EMD Serono Research & Development Institute, Inc. |
Trial Keywords
- M3258
- Dexamethasone
- Pharmacokinetics
- Relapsed Refractory Multiple Myeloma
Last Updated
May 12, 2021