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

Cancer Categories

Karmanos Trial ID

NCT ID

Age Group

Scope

Phase

Principal Investigator

Part 1: Phase 1 Dose Escalation Phase

Primary Objective:

To evaluate the safety and maximum tolerated dose (MTD) of EZM0414 when administered as monotherapy in subjects with relapsed/refractory (R/R) multiple myeloma (MM) and R/R diffuse large B cell lymphoma (DLBCL).

Exploratory Objectives:

To investigate target engagement in samples collected before and during treatment with EZM0414.
To determine exploratory biomarkers such as histones and histone methylation, somatic mutations, DNA methylation, DNA alterations such as t(4;14) and others, protein levels, RNA expression, and immune cells in bone marrow aspirates, tumor biopsies, and blood samples.
To assess pharmacokinetics (PK) of EZM0414 when administered as monotherapy in subjects with R/R MM and R/R DLBCL.

Part 2: Phase 1b Dose Expansion Phase

Primary Objectives:

To determine the safety and tolerability of EZM0414 in subjects with R/R MM and R/R DLBCL.
To establish the recommended Phase 2 dose (RP2D).

Secondary Objectives:

To determine the efficacy of EZM0414 as demonstrated by the effect on objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR) in subjects with R/R MM and R/R DLBCL.

Exploratory Objective:

To determine H3K36me3 in tumor tissue biopsy/bone marrow biopsy and blood samples.
To determine exploratory biomarkers such as histones and histone methylation, somatic mutations, DNA methylation and other DNA alterations such as t(4;14) and others, protein levels, RNA expression, and immune cells in bone marrow aspirates, tumor biopsies, and blood samples.
To determine the pharmacokinetic profile of EZM0414.

Eligibility

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.
Subjects must be ≥18 years of age at the time of signing the ICF (Informed Consent Form).
Subjects must have an Eastern Cooperative Oncology Group (ECOG) status of 0 - 2.
For MM, subjects must have measurable disease by IMWG (International Myeloma Working Group) 2016 criteria
For DLBCL, subjects must have measurable disease by Lugano criteria
Females must not be breastfeeding or pregnant at screening
Females of childbearing potential must not have had unprotected sexual intercourse while participating in this study
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:

Subjects with plasma cell leukemia defined as a plasma cell count >2000/mm3.
Subjects with Waldenstrom's macroglobulinemia or smoldering MM.
Subjects who had prior treatment with SETD2 or NSD2 inhibitor.
Subjects with active acute or chronic systemic infection requiring systemic treatment, including COVID-19.
Has cardiovascular impairment
Prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 480 msec or history of long QT syndrome.
Known left ventricular ejection fraction (LVEF) < 50% by either echocardiogram (ECHO) or multigated acquisition (MUGA).
Prior major surgery within 4 weeks of treatment start.
Known hypersensitivity to components of the investigational product.
Subjects who have received treatment with any unapproved drug product within 4 weeks prior to screening.
Current participation in any other interventional clinical study except for follow up.
Subjects with a history of or active malignancy other than disease under study
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.
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

Locations

4100 John R
Detroit, MI 48201
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Phone: 800-527-6266

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices