A Study in Subjects With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Study Details
Study Description
Brief Summary
This is a first-in-human (FIH), 2-part, open-label, multi-center, Phase 1/1b safety, tolerability, pharmacokinetics (PK), and efficacy study of oral SETD2 inhibitor, EZM0414, in subjects with relapsed/refractory (R/R) Multiple Myeloma (MM) and R/R Diffuse Large B-Cell Lymphoma (DLBCL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
The first part of the study will be a Phase 1 dose-escalation designed to evaluate the safety, tolerability, and PK of EZM0414 in subjects with R/R MM and R/R DLBCL. Six dose levels starting at 100 mg, then 200 mg, 300 mg, 400 mg, 600 mg, and 900 mg as well as an optional step-down dose of 75 mg (if needed) will be tested. The second part of the study is the Phase 1b dose expansion at the MTD designed to evaluate safety and efficacy in subjects with R/R DLBCL and R/R MM with or without select genetic translocation. Dose expansion will enroll subjects in 3 cohorts: Cohort 1 for R/R MM subjects with t(4;14), Cohort 2 for R/R MM subjects without t(4;14), and Cohort 3 for subjects with R/R DLBCL.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Open-label EZM0414
|
Drug: EZM0414
Formulation: 25 mg and 200 mg immediate-release film-coated tablets
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0 [Through study completion, an average of 3 years]
Severity of adverse events experienced by all subjects with at least 1 dose or partial dose of EZM0414 and DLT (Dose Limiting Toxicity) will be evaluated by the Investigator based on the CTCAE, version 5.0
- Establishing Maximum Tolerated Dose (MTD) and a recommended Phase 2 Dose (RP2D) [Through study completion, an average of 3 years]
Determine MTD and select a dose for further evaluation in phase 2 (RP2D)
- Efficacy of EZM0414 as demonstrated by the effect on objective response rate (ORR) in subjects with R/R MM and R/R DLBCL [Through study completion, an average of 3 years]
ORR defined as the proportion of responders as assessed by Investigator per IMWG 2016 guidelines for MM or Lugano 2014 guidelines for DLBCL
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
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Subjects must be ≥18 years of age at the time of signing the ICF (Informed Consent Form).
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Subjects must have an Eastern Cooperative Oncology Group status of 0 - 2.
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For MM, subjects must have measurable disease by IMWG (International Myeloma Working Group) 2016 criteria
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For DLBCL, subjects must have measurable disease by Lugano criteria
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Females must not be breastfeeding or pregnant at screening
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Females of childbearing potential must not have had unprotected sexual intercourse while participating in this study
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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
Exclusion Criteria:
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Subjects with plasma cell leukemia defined as a plasma cell count >2000/mm3.
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Subjects with Waldenstrom's macroglobulinemia or smoldering MM.
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Subjects who had prior treatment with SETD2 or NSD2 inhibitor.
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Subjects with active acute or chronic systemic infection requiring systemic treatment, including COVID-19.
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Has cardiovascular impairment
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Prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 480 msec or history of long QT syndrome.
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Known left ventricular ejection fraction (LVEF) < 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA).
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Prior major surgery within 4 weeks of treatment start.
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Known hypersensitivity to components of the investigational product.
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Subjects who have received treatment with any unapproved drug product within 4 weeks prior to screening.
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Current participation in any other interventional clinical study except for follow up.
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Subjects with a history of or active malignancy other than disease under study
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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.
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rcca Md Llc | Chevy Chase | Maryland | United States | 20815 |
| 2 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02215 |
| 3 | Astera Cancer Care | East Brunswick | New Jersey | United States | 08816 |
| 4 | Regional Cancer Care Associates LLC - Freehold | Freehold | New Jersey | United States | 07728 |
| 5 | Weill Cornell Medicine | New York | New York | United States | 10021 |
| 6 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
| 7 | NEXT Virginia | Fairfax | Virginia | United States | 22031 |
Sponsors and Collaborators
- Epizyme, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SET-101