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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05121103




Registration number
NCT05121103
Ethics application status
Date submitted
18/10/2021
Date registered
16/11/2021
Date last updated
30/10/2024

Titles & IDs
Public title
A Study of the Safety, Tolerability and Effectiveness of EZM0414 Investigative Product in Participants With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B Cell Lymphoma
Scientific title
A Phase 1/1b, Open-Label, Multi-Center, Two-Part Study of SETD2 Inhibitor EZM0414 in Subjects With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Secondary ID [1] 0 0
SET-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Myeloma, Refractory 0 0
Diffuse Large B-Cell Lymphoma 0 0
Diffuse Large B Cell Lymphoma Refractory 0 0
Multiple Myeloma in Relapse 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - EZM0414

Experimental: Open-label EZM0414 - Participants will receive EZM0414 in continuous 28-day cycles. EZM0414 will be administered orally once daily (QD) without food.

Participants who receive EZM0414 at Maximum tolerated dose (MTD) and do not have Dose limiting toxicities (DLT) in the dose escalation part of the study will be rolled over to a cohort of this dose expansion part.

Cohort 1 for R/R MM Participants. Cohort 2 for R/R MM Participants. Cohort 3 for Participants with R/R DLBCL.


Treatment: Drugs: EZM0414
Immediate-release film-coated tablets: Six dose levels starting at 100 mg, and then 200 mg, 300 mg, 400 mg, 600 mg, and 900 mg as well as an optional step-down dose level of 75 mg (if needed)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants with Adverse Events (AEs)
Timepoint [1] 0 0
Through study completion, an average of 3 years
Primary outcome [2] 0 0
Percentage of participants with clinically significant changes in physical examination
Timepoint [2] 0 0
Through study completion, an average of 3 years
Primary outcome [3] 0 0
Percentage of participants with clinically significant changes in vital signs
Timepoint [3] 0 0
Through study completion, an average of 3 years
Primary outcome [4] 0 0
Percentage of participants with clinically significant changes in 12-lead ECG readings
Timepoint [4] 0 0
Through study completion, an average of 3 years
Primary outcome [5] 0 0
Percentage of participants with clinically significant changes in laboratory parameters (hematology including coagulation profile, serum chemistries, and urinalysis)
Timepoint [5] 0 0
Through study completion, an average of 3 years
Primary outcome [6] 0 0
Performance status evaluated by ECOG
Timepoint [6] 0 0
Through study completion, an average of 3 years
Primary outcome [7] 0 0
Concomitant medication monitoring
Timepoint [7] 0 0
Through study completion, an average of 3 years
Primary outcome [8] 0 0
Part 1 Phase 1: Dose limiting toxicities (DLT)
Timepoint [8] 0 0
Through study completion, an average of 3 years
Primary outcome [9] 0 0
Part 2 Phase 1b: Establishing Maximum Tolerated Dose (MTD) and a recommended Phase 2 Dose (RP2D)
Timepoint [9] 0 0
Through study completion, an average of 3 years
Primary outcome [10] 0 0
Part 2 Phase 1b: Objective Response Rate (ORR)
Timepoint [10] 0 0
Through study completion, an average of 3 years
Secondary outcome [1] 0 0
Part 2 Phase 1b: Progression-free survival (PFS)
Timepoint [1] 0 0
Through study completion, an average of 3 years
Secondary outcome [2] 0 0
Part 2 Phase 1b: Disease Control Rate (DCR)
Timepoint [2] 0 0
Through study completion, an average of 3 years
Secondary outcome [3] 0 0
Part 2 Phase 1b: Duration of response (DOR)
Timepoint [3] 0 0
Through study completion, an average of 3 years

Eligibility
Key inclusion criteria
1. Voluntarily provide signed informed consent after review of verbal and written material about the trial and agree to abide with protocol requirements. All study related activities must be carried out after written consent is obtained.
2. Subjects must be =18 years of age at the time of signing the ICF (Informed Consent Form).
3. Subjects must have an Eastern Cooperative Oncology Group (ECOG) status of 0 - 2.
4. For MM, subjects must have measurable disease by IMWG (International Myeloma Working Group) 2016 criteria
5. For DLBCL, subjects must have measurable disease by Lugano criteria
6. Females must not be breastfeeding or pregnant at screening
7. Females of childbearing potential must not have had unprotected sexual intercourse while participating in this study
8. Male subjects must either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy, during study treatment and for 30 days after the final dose of study treatment
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subjects with plasma cell leukemia defined as a plasma cell count >2000/mm3.
2. Subjects with Waldenstrom's macroglobulinemia or smoldering MM.
3. Subjects who had prior treatment with SETD2 or NSD2 inhibitor.
4. Subjects with active acute or chronic systemic infection requiring systemic treatment, including COVID-19.
5. Has cardiovascular impairment
6. Prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 480 msec or history of long QT syndrome.
7. Known left ventricular ejection fraction (LVEF) < 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA).
8. Prior major surgery within 4 weeks of treatment start.
9. Known hypersensitivity to components of the investigational product.
10. Subjects who have received treatment with any unapproved drug product within 4 weeks prior to screening.
11. Current participation in any other interventional clinical study except for follow up.
12. Subjects with a history of or active malignancy other than disease under study
13. Underlying medical/social conditions that in PI opinion will place the subject in significant risk and affect the interpretation of toxicity and adverse events assessments.
14. Inability to take oral medication or known gastrointestinal (GI) disease, GI procedure or medical condition that could interfere with the oral absorption or tolerance of the study drug

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/05/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
30/04/2024
Sample size
Target
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New Jersey
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
Texas
Country [5] 0 0
United States of America
State/province [5] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Epizyme, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study will include participants with relapsed/refractory (R/R) Multiple Myeloma (MM). MM is a type of cancer of the blood. This study will also include participants with relapsed/refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL).

DLBCL is also a type of cancer of the blood. They are referred to as 'relapsed' when the disease has come back after treatment and 'refractory' when treatment no longer works. The study has 2 main parts, called phase 1 and phase 1b. The main objective of both parts will be to evaluate the safety and tolerability of the study drug, called EZM0414.

The main objective of phase 1b will also be to determine the effectiveness of EZM0414. During phase 1 six dose levels will be tested to obtain the most tolerated dose. Participants will receive study drug at the assigned dose level every 28 days. During phase 1b participants will receive study drug at the maximum tolerated dose in 28-day cycles.
Trial website
https://clinicaltrials.gov/study/NCT05121103
Trial related presentations / publications
Public notes
This record is viewable in the ANZCTR as it had previously listed Australia and/or New Zealand as a recruitment site, however these sites have since been removed

Contacts
Principal investigator
Name 0 0
Ipsen Medical Director
Address 0 0
Ipsen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05121103